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Parodis I, Lagutkin D, Lindblom J, Idborg H, Beretta L, Borghi MO, Peyper JM, Barturen G, Jakobsson PJ, Alarcón-Riquelme ME, Sherina N, Nikolopoulos D. New IgG and IgA autoantibody specificities against DNA-binding and RNA-binding proteins discriminate systemic lupus erythematosus from health and non-lupus autoimmunity-could anti-LIN28A enhance precision in diagnostics? Ann Rheum Dis 2025:S0003-4967(25)00889-1. [PMID: 40374430 DOI: 10.1016/j.ard.2025.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 03/30/2025] [Accepted: 04/01/2025] [Indexed: 05/17/2025]
Abstract
OBJECTIVES In response to the urgent unmet needs of heterogeneity, unpredictability, and diagnostic delay in systemic lupus erythematosus (SLE), we aimed to identify and validate new immunoglobulin (Ig)G and IgA autoantibody specificities. METHODS Using a KoRectly EXpressed technology-based microarrays (i-Ome Discovery; Sengenics), we screened for circulating IgG and IgA autoantibodies against 1609 proteins in 2 independent cohorts (discovery: NTC02890121; validation: NCT02890134) comprising patients with SLE (n = 199 and n = 30), primary Sjögren's disease (n = 115 and n = 31), and systemic sclerosis (n = 115 and n = 24), and healthy controls (HCs; n = 111 and n = 84), respectively. RESULTS We identified and validated 5 IgG (anti-Lin-28 homolog A [LIN28A], anti-HNRNPA2B1, anti-HMG20B, anti-HMGB2, and anti-alpha-globin transcription factor CP2 [TFCP2]) and 4 IgA (anti-LIN28A, anti-HMG20B, anti-SUB1, and anti-TFCP2) autoantibodies that demonstrated high specificity for SLE (0.91-0.94), along with consistent and robust positivity (0.22-0.69) in differentially abundant autoantibody (daAAb) analysis between SLE and comparator groups. IgG and IgA anti-LIN28A levels varied over a 14-month follow-up in the validation cohort of newly diagnosed patients with SLE and exhibited metrics that outperformed those of traditional autoantibody markers such as anti-double-stranded DNA. Clustering of patients with SLE based on autoantibody positivity (levels above the HC median plus 2 IQRs in the discovery cohort) status revealed 1 subgroup demonstrating seroreactivity against multiple antigens, 3 exhibiting varying reactivity, and 1 showing no reactivity. In pathway analysis, daAAb targets pointed to DNA-binding and RNA-binding and transcription functions. CONCLUSIONS Novel autoantibodies validated in this study may enhance diagnostics and molecular characterisation in SLE. The prominent IgA seroreactivity implicates important roles of mucosal tissues in SLE autoimmunity, warranting further investigation.
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Affiliation(s)
- Ioannis Parodis
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; Center for Molecular Medicine, Stockholm, Sweden; Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
| | - Denis Lagutkin
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; Center for Molecular Medicine, Stockholm, Sweden
| | - Julius Lindblom
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; Center for Molecular Medicine, Stockholm, Sweden
| | - Helena Idborg
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; Center for Molecular Medicine, Stockholm, Sweden
| | - Lorenzo Beretta
- Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Maria Orietta Borghi
- Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, Milan, Italy; IRCCS, Istituto Auxologico Italiano, Milan, Italy
| | | | - Guillermo Barturen
- GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada/Andalusian Regional Government, Medical Genomics, Granada, Spain; Department of Genetics, Faculty of Sciences, University of Granada, Granada, Spain
| | - Per-Johan Jakobsson
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; Center for Molecular Medicine, Stockholm, Sweden
| | - Marta E Alarcón-Riquelme
- GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada/Andalusian Regional Government, Medical Genomics, Granada, Spain; Department of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Natalia Sherina
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; Center for Molecular Medicine, Stockholm, Sweden
| | - Dionysis Nikolopoulos
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden; Center for Molecular Medicine, Stockholm, Sweden
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2
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Björk A, Wahadat MJ, Sánchez-Blázquez M, Braams M, Rip J, van Tilburg SJ, van Helden-Meeuwsen CG, Kamphuis S, van den Bosch TPP, Brkic Z, Versnel MA. Amlexanox inhibits production of type I interferon and suppresses B cell differentiation in vitro: a possible therapeutic option for systemic lupus erythematosus and other systemic inflammatory diseases. RMD Open 2025; 11:e005351. [PMID: 40341181 PMCID: PMC12060889 DOI: 10.1136/rmdopen-2024-005351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 04/24/2025] [Indexed: 05/10/2025] Open
Abstract
OBJECTIVES Activation of the type I interferon (IFN) pathway and autoreactive B cells are key immunopathogenic features of systemic lupus erythematosus (SLE), primary Sjögren's disease (pSjD) and systemic sclerosis (SSc). TANK-binding kinase 1 (TBK1) is a mediator of type I IFN and essential during B cell development in mice. We investigated the properties of the TBK1 inhibitor amlexanox in systemic autoimmune diseases. METHODS The effects of amlexanox on peripheral blood mononuclear cells (PBMCs) stimulated with Imiquimod, CpG-A, Poly:IC, G3-YsD and 3p-hpRNA were assessed. B cells from healthy controls and patients with SLE, pSjD and SSc were cultured with CD40L, IL-21, IFN, B cell activating factor (BAFF) and amlexanox. Differentiation into CD38highCD27highCD138+/- cells, proliferation, and IgM and IgG production were measured. RESULTS Amlexanox inhibited production of type I IFN induced through endosomal and cytosolic routes in PBMCs. Likewise, supernatants from amlexanox-treated cells did not induce expression of BAFF and MX1. Amlexanox inhibited spontaneous MX1 expression in PBMCs from SLE, pSjD and SSc patients. Immunohistochemical staining confirmed expression of the TBK1 protein in pSjD salivary glands. Using a B cell differentiation assay, addition of amlexanox decreased B cell proliferation and differentiation into CD27highCD38highCD138+/- plasmablasts and plasma cells. Correspondingly, production of IgM and IgG was suppressed. The observations were corroborated in B cells from patients with SLE, pSjD and SSc. CONCLUSIONS Our findings demonstrate inhibitory effects of amlexanox on type I IFN production and B cell differentiation in primary human cells. Inhibition of TBK1 could potentially be a therapeutic option for the treatment of type I IFN-driven systemic inflammatory diseases.
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MESH Headings
- Humans
- Interferon Type I/metabolism
- B-Lymphocytes/drug effects
- B-Lymphocytes/immunology
- B-Lymphocytes/metabolism
- B-Lymphocytes/cytology
- Lupus Erythematosus, Systemic/drug therapy
- Lupus Erythematosus, Systemic/immunology
- Lupus Erythematosus, Systemic/metabolism
- Cell Differentiation/drug effects
- Aminopyridines/pharmacology
- Female
- Protein Serine-Threonine Kinases/antagonists & inhibitors
- Protein Serine-Threonine Kinases/metabolism
- Adult
- Middle Aged
- Male
- Scleroderma, Systemic/drug therapy
- Scleroderma, Systemic/immunology
- Scleroderma, Systemic/metabolism
- Cells, Cultured
- Leukocytes, Mononuclear/drug effects
- Leukocytes, Mononuclear/metabolism
- Leukocytes, Mononuclear/immunology
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Affiliation(s)
- Albin Björk
- Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Center for Rheumatology, Academic Specialist Center, Stockholm, Sweden
| | - Mohamed Javad Wahadat
- Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
- Department of Pediatric Rheumatology, Sophia Children's Hospital, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Maria Sánchez-Blázquez
- Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Merijn Braams
- Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jasper Rip
- Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
- MS Center ErasMS, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Sander J van Tilburg
- Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | | | - Sylvia Kamphuis
- Department of Pediatric Rheumatology, Sophia Children's Hospital, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Thierry P P van den Bosch
- Department of Pathology and Clinical Bioinformatics, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Zana Brkic
- Department of Internal Medicine, Division of Clinical Immunology and Allergology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Marjan A Versnel
- Department of Immunology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
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Yang Y, Zhang Y, Liu K, Liu M, Zhang H, Guo M. IFI27, a potential candidate molecular marker for primary Sjogren's syndrome. Clin Rheumatol 2025; 44:1949-1960. [PMID: 40146445 DOI: 10.1007/s10067-025-07409-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 03/04/2025] [Accepted: 03/18/2025] [Indexed: 03/28/2025]
Abstract
OBJECTIVE The etiology of primary Sjogren's syndrome (pSS) is complex and not completely clear. This study was to identify key genes in pSS based on Gene Expression Omnibus (GEO). METHODS We downloaded the GSE40568, GSE80805, GSE127952, and GSE164885 mRNA expression profiles from GEO. Differentially expressed genes (DEGs) analyses were carried out by using the online analysis tool GEO2R and R. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the biological processes, molecular function, cellular component, and KEGG signaling pathways for the DEGs in salivary glands (SGs) and peripheral blood mononuclear cells (PBMCs). Genes co-expressed were found in PBMCs and SGs of pSS patients. RT-qPCR was performed for validation. Finally, clinical correlation analysis and receiver operator characteristic (ROC) curve analysis were performed. RESULTS A total of thirty-nine up-regulated and one down-regulated genes were identified in pSS SGs. GO and KEGG pathway revealed that these DEGs were related to response to virus, and type I interferon signaling pathway. It was verified that fourteen genes were up-regulated in the SGs of pSS by RT-qPCR. Twenty up-regulated genes were identified in pSS patients PBMCs. Two genes were up-regulated in SGs and PBMCs of pSS patients, including IFI27 and IFI44L. The mRNA level of IFI27 was positively correlated with the disease activity of pSS patients. Furthermore, ROC analyses proved IFI27 may have diagnostic value for pSS. CONCLUSION IFI27 might serve as a potential biomarker for the early diagnosis and therapy of pSS. Key Points • IFI27 expression was significantly increased in PBMCs and SGs of pSS patients. • IFI27 was positively correlated with disease activity in pSS patients. • IFI27 might have a good diagnostic value for pSS.
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Affiliation(s)
- Yiying Yang
- Department of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medicine Science, Central South University, 410000, Changsha, Hunan, China
- Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China
- National Medicine Functional Experimental Teaching Center, Central South University, Changsha, Hunan, China
- Postdoctoral Research Station of Biology, School of Basic Medicine Science, Central South University, Changsha, Hunan, China
| | - Ying Zhang
- Department of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medicine Science, Central South University, 410000, Changsha, Hunan, China
- Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China
- National Medicine Functional Experimental Teaching Center, Central South University, Changsha, Hunan, China
| | - Ke Liu
- Department of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medicine Science, Central South University, 410000, Changsha, Hunan, China
- Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China
- National Medicine Functional Experimental Teaching Center, Central South University, Changsha, Hunan, China
| | - Meidong Liu
- Department of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medicine Science, Central South University, 410000, Changsha, Hunan, China
- Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China
- National Medicine Functional Experimental Teaching Center, Central South University, Changsha, Hunan, China
| | - Huali Zhang
- Department of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medicine Science, Central South University, 410000, Changsha, Hunan, China
- Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China
- National Medicine Functional Experimental Teaching Center, Central South University, Changsha, Hunan, China
| | - Muyao Guo
- Department of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medicine Science, Central South University, 410000, Changsha, Hunan, China.
- Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
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4
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Wang Y, Wu GR, Yue H, Zhou Q, Zhang L, He L, Gu W, Gao R, Dong L, Zhang H, Zhao J, Liu X, Xiong W, Wang CY. Kynurenine acts as a signaling molecule to attenuate pulmonary fibrosis by enhancing the AHR-PTEN axis. J Adv Res 2025; 71:521-532. [PMID: 38906325 DOI: 10.1016/j.jare.2024.06.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 05/28/2024] [Accepted: 06/18/2024] [Indexed: 06/23/2024] Open
Abstract
INTRODUCTION Pulmonary fibrosis (PF) is a fatal fibrotic lung disease without any options to halt disease progression. Feasible evidence suggests that aberrant metabolism of amino acids may play a role in the pathoetiology of PF. However, the exact impact of kynurenine (Kyn), a metabolite derived from tryptophan (Trp) on PF is yet to be addressed. OBJECTIVES This study aims to elucidate the role of kynurenine in both the onset and advancement of PF. METHODS Liquid chromatography-tandem mass spectrometry was employed to assess Kyn levels in patients with idiopathic PF and PF associated with Sjögren's syndrome. Additionally, a mouse model of PF induced by bleomycin was utilized to study the impact of Kyn administration. Furthermore, cell models treated with TGF-β1 were used to explore the mechanism by which Kyn inhibits fibroblast functions. RESULTS We demonstrated that high levels of Kyn are a clinical feature in both idiopathic PF patients and primary Sjögren syndrome associated PF patients. Further studies illustrated that Kyn served as a braking molecule to suppress fibroblast functionality, thereby protecting mice from bleomycin-induced lung fibrosis. The protective effects depend on AHR, in which Kyn induces AHR nuclear translocation, where it upregulates PTEN expression to blunt TGF-β mediated AKT/mTOR signaling in fibroblasts. However, in fibrotic microenviroment, the expression of AHR is repressed by methyl-CpG-binding domain 2 (MBD2), a reader interpreting the effect of DNA methylation, which results in a significantly reduced sensitivity of Kyn to fibroblasts. Therefore, exogenous administration of Kyn substantially reversed established PF. CONCLUSION Our studies not only highlighted a critical role of Trp metabolism in PF pathogenesis, but also provided compelling evidence suggesting that Kyn could serve as a promising metabolite against PF.
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Affiliation(s)
- Yi Wang
- Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, National Health Commission Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Guo-Rao Wu
- Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, National Health Commission Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Huihui Yue
- Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, National Health Commission Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Qing Zhou
- Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, National Health Commission Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Lei Zhang
- Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, National Health Commission Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Long He
- Department of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200011, China
| | - Weikuan Gu
- Department of Orthopedic Surgery and BME-Campbell Clinic, University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Rongfen Gao
- Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Lingli Dong
- Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Huilan Zhang
- Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, National Health Commission Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Jianping Zhao
- Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, National Health Commission Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China
| | - Xiansheng Liu
- Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China.
| | - Weining Xiong
- Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, National Health Commission Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China; Department of Respiratory and Critical Care Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Lu, Shanghai 200011, China.
| | - Cong-Yi Wang
- Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China; Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, the Key Laboratory of Endocrine and Metabolic Diseases of Shanxi Province, Taiyuan, China; The Center for Biomedical Research, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Gjølberg TT, Mester S, Calamera G, Telstad JS, Sandlie I, Andersen JT. Targeting the Neonatal Fc Receptor in Autoimmune Diseases: Pipeline and Progress. BioDrugs 2025; 39:373-409. [PMID: 40156757 PMCID: PMC12031853 DOI: 10.1007/s40259-025-00708-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2025] [Indexed: 04/01/2025]
Abstract
Autoimmune diseases are highly prevalent and affect people at all ages, women more often than men. The most prominent immunological manifestation is the production of antibodies directed against self-antigens. In many cases, these antibodies (Abs) drive the pathogenesis by attacking the body's own healthy cells, causing serious health problems that may be life threatening. Most autoantibodies are of the immunoglobulin G (IgG) isotype, which has a long plasma half-life and potent effector functions. Thus, there is a need for specific treatment options that rapidly eliminate these pathogenic IgG auto-Abs. In this review, we discuss how the neonatal Fc receptor (FcRn) acts as a regulator of the high levels of not only IgG Abs, but also albumin, by rescuing both these soluble proteins from cellular catabolism, and how a molecular and cellular understanding of this complex biology has spurred an intense interest in the development of FcRn-targeting strategies for the treatment of IgG-driven autoimmune diseases. We find that this emerging therapeutic class demonstrates efficacy within several autoimmune diseases with distinct pathophysiology. This offers hope for both new therapeutic avenues for highly prevalent diseases currently treated by other means, and rare diseases with no approved therapies to date. In addition, we elaborate on studies that have led to approval of the first FcRn antagonists, the clinical progress and structural design of molecules in the pipeline, their position in the overall therapeutic landscape of autoimmunity, the design of next-generation antagonists as well as the use of this receptor-targeting principle for other therapeutic applications.
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Affiliation(s)
- Torleif Tollefsrud Gjølberg
- Authera AS, 0349, Oslo, Norway.
- Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, 0372, Oslo, Norway.
- Department of Immunology, Oslo University Hospital and University of Oslo, 0372, Oslo, Norway.
- Precision Immunotherapy Alliance (PRIMA), University of Oslo, Oslo, Norway.
| | - Simone Mester
- Authera AS, 0349, Oslo, Norway
- Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, 0372, Oslo, Norway
- Department of Immunology, Oslo University Hospital and University of Oslo, 0372, Oslo, Norway
- Precision Immunotherapy Alliance (PRIMA), University of Oslo, Oslo, Norway
| | | | | | - Inger Sandlie
- Department of Biosciences, University of Oslo, 0316, Oslo, Norway
| | - Jan Terje Andersen
- Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, 0372, Oslo, Norway.
- Department of Immunology, Oslo University Hospital and University of Oslo, 0372, Oslo, Norway.
- Precision Immunotherapy Alliance (PRIMA), University of Oslo, Oslo, Norway.
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Dörner T, Bowman SJ, Fox R, Mariette X, Papas A, Grader-Beck T, Fisher BA, Barcelos F, De Vita S, Schulze-Koops H, Moots RJ, Junge G, Woznicki J, Sopala M, Avrameas A, Luo WL, Hueber W. Safety and Efficacy of Ianalumab in Patients With Sjögren's Disease: 52-Week Results From a Randomized, Placebo-Controlled, Phase 2b Dose-Ranging Study. Arthritis Rheumatol 2025; 77:560-570. [PMID: 39557617 DOI: 10.1002/art.43059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 09/16/2024] [Accepted: 11/06/2024] [Indexed: 11/20/2024]
Abstract
OBJECTIVE The objective of this study was to report 52-week safety and efficacy of ianalumab from phase 2b dose-finding study in patients with Sjögren's disease (SjD). METHODS Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks until week 24 (treatment period [TP]1). At week 24, patients on 300 mg were rerandomized to continue 300 mg or receive placebo until week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, and patients on 5 and 50 mg directly entered posttreatment safety follow-up. Patients who discontinued treatment early or completed treatment entered safety follow-up (≥20 weeks). RESULTS During TP1, 190 patients were randomized (placebo = 49, 5 mg = 47, 50 mg = 47, 300 mg = 47). Of these 190 patients, 90 (47.4 %; 43 continued 300 mg and 47 received placebo) entered TP2, and 81 of 90 (90.0%) completed the study treatment. By week 52, efficacy was sustained in patients who continued 300 mg in TP2 (EULAR Sjögren's Syndrome Disease Activity Index, EULAR Sjögren's Syndrome Patient Reported Index, patient global assessment, and physician global assessment change from week 24: -1.45, -0.46, -4.69, and -6.86, respectively). Stimulated salivary flow rates and autoantibody levels numerically improved in the 300 mg group. Treatment-emergent adverse events were not dose-dependent, except for injection-site reactions. Cases of decreased neutrophil counts (Common Terminology Criteria for Adverse Events v4.03 grade 3 according to laboratory listings) were observed in three patients during the posttreatment follow-up, occurring at 3.5, 5.5, and 3 months, after the last ianalumab administration. None were associated with infection except one incidental finding of asymptomatic cytomegalovirus infection (IgM-positive). CONCLUSION In patients with SjD, ianalumab 300 mg demonstrated sustained efficacy through week 52 and a favorable safety profile up to two years of follow-up.
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Affiliation(s)
| | - Simon J Bowman
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Robert Fox
- Scripps Memorial Hospital and Research Institute, La Jolla, California
| | - Xavier Mariette
- Université Paris-Saclay, Paris, France, and Hôpital Bicêtre, AP-HP, Le Kremlin Bicêtre, France
| | - Athena Papas
- Tufts School of Dental Medicine, Boston, Massachusetts
| | | | - Benjamin A Fisher
- University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, and NIHR Birmingham Biomedical Research Centre, Birmingham, United Kingdom
| | | | | | | | - Robert J Moots
- Aintree University Hospital, Liverpool, United Kingdom, and Edge Hill University, Ormskirk, United Kingdom
| | | | - Janice Woznicki
- Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
| | | | | | - Wen-Lin Luo
- Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
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7
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St Clair EW. Living With Sjögren Disease: Prospects for Disease-Modifying Therapies. Arthritis Rheumatol 2025; 77:499-502. [PMID: 39557621 DOI: 10.1002/art.43060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 11/02/2024] [Accepted: 11/06/2024] [Indexed: 11/20/2024]
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8
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Zhong W, Zhang H, Ran H. The Value of Lacrimal Gland Ultrasonography and Shear Wave Elastography in the Evaluation of Primary Sjögren's Syndrome: A Cross-Sectional Study. JOURNAL OF CLINICAL ULTRASOUND : JCU 2025; 53:685-694. [PMID: 39876779 DOI: 10.1002/jcu.23926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 11/11/2024] [Accepted: 12/03/2024] [Indexed: 01/31/2025]
Abstract
PURPOSE This study evaluates the effectiveness of lacrimal gland ultrasonography (LGUS) and shear wave elastography (SWE) in distinguishing primary Sjögren's syndrome (PSS) patients from healthy controls and examines their role in assessing disease activity and prognosis. METHODS A total of 35 PSS patients and 23 age- and gender-matched healthy controls were included. LGUS was used to grade lacrimal gland structure, while SWE assessed gland elasticity. Disease activity and prognosis were evaluated using european league against rheumatism sjögren's syndrome disease activity index (ESSDAI) and serologic markers. RESULTS Compared with healthy controls, LGUS, Emean, and shear wave velocity (SWV) were significantly higher in PSS patients. The optimal cut-off value of LGUS for diagnosis of PSS was 2 (area under the curve [AUC]: 0.832, sensitivity: 80.0%, specificity: 69.6%), the optimal thresholds for diagnosis of PSS using Emean and SWV values are 9.4 kPa (AUC: 0.768, sensitivity: 65.7%, specificity: 82.6%) and 1.7 m/s (AUC: 0.823, sensitivity: 71.4%, specificity: 91.3%), respectively. There are statistical differences in Emean and SWV between subgroups based on european league against rheumatism sjögren's syndrome disease activity index (ESSDAI); there are statistical differences in LGUS, Emean, and SWV between subgroups based on IgG levels and complement titers. CONCLUSION LGUS and SWE are accurate, noninvasive diagnostic tools for PSS and may serve as indicators of disease activity and prognosis.
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Affiliation(s)
- Wenxing Zhong
- Department of Ultrasonography, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hua Zhang
- Department of Ultrasonography, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Haitao Ran
- Department of Ultrasonography, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Qi X, Zhao D, Wang N, Han Y, Huang B, Feng R, Jin Y, Wang R, Lin X, He J. B lymphocyte subset-based stratification in primary Sjögren's syndrome: implications for lymphoma risk and personalized treatment. Clin Rheumatol 2025:10.1007/s10067-025-07434-8. [PMID: 40295463 DOI: 10.1007/s10067-025-07434-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 03/30/2025] [Accepted: 04/07/2025] [Indexed: 04/30/2025]
Abstract
OBJECTIVE This study aimed to perform a detailed stratification analysis of B lymphocyte subsets in patients with primary Sjögren's syndrome (pSS) and to investigate their associations with lymphoma risk, clinical phenotypes, and disease activity. METHODS In this retrospective study, we analyzed data from 137 patients with pSS. We employed machine learning approaches, specifically principal component analysis (PCA) and k-means clustering, to examine B lymphocyte subset distributions from flow cytometry data and immunoglobulin IgG and complement (C3, C4) levels. The optimal cluster number was determined using the Elbow Method in R software. Based on these 10 variables, patients were categorized into distinct subgroups. We then comprehensively compared clinical characteristics, laboratory parameters, and disease activity indices among these identified subgroups. RESULTS Four distinct subgroups were identified. Cluster A exhibited a significantly higher lymphoma incidence rate of 20%, compared to 3.39% in Cluster B and 0% in Clusters C and D (p = 0.007). Cluster A also had the highest percentage of double-negative B cells (32.26 ± 17.96%) and plasma cells (2.02 ± 1.92%). ESSDAI scores indicated that disease activity was highest in Cluster A (9.00, 6.00-20.00), followed by Clusters B (7.00, 3.50-14.00), C (6.00, 1.25-17.50), and D (5.00, 1.50-9.00), respectively. CONCLUSION This innovative stratification method revealed the critical role of B cell subset imbalance in the pathogenesis of pSS and provided new evidence for predicting lymphoma risk and guiding personalized treatment. Key Points • Identifying a distinct patient subgroup with elevated lymphoma risk and increased disease activity could aid in risk prediction. • Applying machine learning techniques to stratify B cell populations provides insights into pSS pathogenesis. • A proposed framework for personalized treatment approaches based on B cell subset imbalances in pSS.
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Affiliation(s)
- Xuan Qi
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
- Department of Rheumatism and Immunology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Doudou Zhao
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
- Department of Rheumatism and Immunology, Jincheng People's Hospital, Jincheng, Shanxi, China
| | - Naidi Wang
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
| | - Yipeng Han
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
| | - Bo Huang
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
| | - Ruiling Feng
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
| | - Yuebo Jin
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
| | - Ruoyi Wang
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
| | - Xiang Lin
- School of Chinese Medicine, the University of Hong Kong, Hong Kong, China
| | - Jing He
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
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10
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You W, Xu L, Gao Y, Youshen Z, Yao G. Quantitative assessment of salivary gland scintigraphy with SPECT/CT in the clinical application of Sjögren's syndrome. Z Rheumatol 2025:10.1007/s00393-025-01649-5. [PMID: 40266372 DOI: 10.1007/s00393-025-01649-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/19/2025] [Indexed: 04/24/2025]
Abstract
OBJECTIVE This study aims to investigate the feasibility and clinical value of single-photon-emission computed tomography/computed tomography (SPECT/CT) in the quantitative assessment of salivary gland function in patients with Sjögren's syndrome (SS). MATERIALS AND METHODS Data were collected from 84 patients diagnosed with SS who underwent dynamic salivary gland scintigraphy at the First Affiliated Hospital of Anhui University of Science and Technology between October 2020 and October 2023. Additionally, a control group of 25 thyroid cancer patients who underwent thyroidectomy was selected. Imaging data from dynamic salivary gland scintigraphy were obtained and analyzed to calculate salivary gland functional parameters, including maximum accumulation rate (MAR), uptake ratio (UR), maximum secretion rate (MSR), Tmin (time from peak to lowest point on the time-activity curve), and average secretion rate (Vmin) following acidic stimulation. RESULTS Significant differences in MAR, UR, MSR, Vmin, and Tmin of the parotid and submandibular glands were observed between the SS group and the control group (P < 0.05). In the mild impairment group, significant differences were found in MSR, Tmin, and Vmin of the submandibular gland compared to the control group (P < 0.05). Moderate and severe impairment groups exhibited significant differences in MAR, MSR, Tmin, UR, and Vmin of the parotid gland compared to the control group (P < 0.05). CONCLUSION In SS patients, MAR, UR, MSR, Vmin, and Tmin are important indicators for evaluating salivary gland damage. The qualitative analysis of SPECT/CT salivary gland dynamic imaging and time-activity curves effectively assesses salivary gland function in SS patients, providing vital information for the development of clinical treatment strategies.
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Affiliation(s)
- Wei You
- Department of Nuclear Medicine, The First Hospital of Anhui University of Science and Technology (The First People's Hospital of Huainan), 232000, Huainan, Anhui Province, China
- The Medical School of Anhui University of Science & Technology, 232000, Huainan, Anhui Province, China
| | - Lei Xu
- Department of Nuclear Medicine, The First Hospital of Anhui University of Science and Technology (The First People's Hospital of Huainan), 232000, Huainan, Anhui Province, China
| | - Ya Gao
- Department of Nuclear Medicine, The First Hospital of Anhui University of Science and Technology (The First People's Hospital of Huainan), 232000, Huainan, Anhui Province, China
| | - Zeng Youshen
- Department of Nuclear Medicine, The First Hospital of Anhui University of Science and Technology (The First People's Hospital of Huainan), 232000, Huainan, Anhui Province, China
| | - Guoling Yao
- Department of Nuclear Medicine, The First Hospital of Anhui University of Science and Technology (The First People's Hospital of Huainan), 232000, Huainan, Anhui Province, China.
- The Medical School of Anhui University of Science & Technology, 232000, Huainan, Anhui Province, China.
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Barbalace MC, Talotta R, Rapisarda F, D’Amico V, Laganà M, Malaguti M, Campennì A, Cannavò S, Hrelia S, Ruggeri RM. Unlocking the Power of the Mediterranean Diet: Two in One-Dual Benefits for Rheumatic and Thyroid Autoimmune Diseases. Nutrients 2025; 17:1383. [PMID: 40284245 PMCID: PMC12030468 DOI: 10.3390/nu17081383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2025] [Revised: 04/14/2025] [Accepted: 04/15/2025] [Indexed: 04/29/2025] Open
Abstract
In recent years, autoimmune diseases are becoming more and more prevalent worldwide, with this rapid rise being influenced by environmental factors linked to lifestyle changes in modern societies. In this context, the role of diet has been the topic of extensive research as evidence has mounted that particular dietary patterns may contribute to or modulate autoimmunity. The present review specifically focuses on the Mediterranean diet (MD) as a whole dietary pattern, and on its peculiar components, such as n-3 polyunsaturated fatty acids (PUFAs), polyphenols and fiber. We explored their potential benefits in a spectrum of both systemic and organ-specific autoimmune disorders, including rheumatic diseases (like rheumatic arthritis and systemic lupus erythematosus), and thyroid diseases (like Hashimoto's thyroiditis), since they often occur in the same individuals. Here, we offer a comprehensive review about the influence of dietary factors on these autoimmune diseases and potential translation into therapeutic interventions, as an adjuvant therapeutic approach to improve autoimmunity-related outcomes.
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Affiliation(s)
- Maria Cristina Barbalace
- Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, 47921 Rimini, Italy; (M.M.); (S.H.)
| | - Rossella Talotta
- Rheumatology Unit, Department of Clinical and Experimental Medicine, University Hospital “G. Martino”, 98124 Messina, Italy; (R.T.); (F.R.); (V.D.)
| | - Federica Rapisarda
- Rheumatology Unit, Department of Clinical and Experimental Medicine, University Hospital “G. Martino”, 98124 Messina, Italy; (R.T.); (F.R.); (V.D.)
| | - Valeria D’Amico
- Rheumatology Unit, Department of Clinical and Experimental Medicine, University Hospital “G. Martino”, 98124 Messina, Italy; (R.T.); (F.R.); (V.D.)
| | - Martina Laganà
- Endocrinology Unit, Department of Human Pathology of Adulthood and Childhood DETEV “G. Barresi”, University of Messina, 98125 Messina, Italy; (M.L.); (S.C.); (R.M.R.)
| | - Marco Malaguti
- Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, 47921 Rimini, Italy; (M.M.); (S.H.)
| | - Alfredo Campennì
- Unit of Nuclear Medicine, Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, 98125 Messina, Italy;
| | - Salvatore Cannavò
- Endocrinology Unit, Department of Human Pathology of Adulthood and Childhood DETEV “G. Barresi”, University of Messina, 98125 Messina, Italy; (M.L.); (S.C.); (R.M.R.)
| | - Silvana Hrelia
- Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, 47921 Rimini, Italy; (M.M.); (S.H.)
| | - Rosaria Maddalena Ruggeri
- Endocrinology Unit, Department of Human Pathology of Adulthood and Childhood DETEV “G. Barresi”, University of Messina, 98125 Messina, Italy; (M.L.); (S.C.); (R.M.R.)
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12
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Yang X, Yu C, Zhang X, Wu C, Peng Z, Gai Y, Peng J, Zhou S, Song L, Huang H, Xu D, Zhao J, Tian X, Duan X, Zeng X, Li M, Wang Q. The Prospective Registry of MyositIS (PROMIS): I. Next-generation sequencing identifies HLA-DQA1 as a novel genetic risk of anti-MDA5 antibody-positive dermatomyositis. Ann Rheum Dis 2025:S0003-4967(25)00811-8. [PMID: 40246682 DOI: 10.1016/j.ard.2025.02.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 01/17/2025] [Accepted: 02/19/2025] [Indexed: 04/19/2025]
Abstract
OBJECTIVES Antimelanoma differentiation-associated gene 5-positive dermatomyositis (anti-MDA5+ DM) is a rare subtype of myositis with a poor prognosis and insufficient genetic understanding. Our study aimed to identify risk variants associated with anti-MDA5+ DM and to assess their correlation with clinical outcomes. METHODS We enrolled 231 anti-MDA5+ DM patients, 127 anti-MDA5⁻ DM patients, 1468 patients with non-DM rheumatic disease, and 1027 healthy controls, with an additional 51 anti-MDA5+ DM patients for validation. Whole-exome sequencing was used to identify human leukocyte antigen (HLA) alleles, amino acids, and single nucleotide polymorphisms (SNPs) in major histocompatibility complex (MHC) and non-MHC regions. Association studies were performed to identify genetic variants associated with anti-MDA5+ DM by comparing different sets of control groups. A clinical association study was conducted to further explore the influence of genetic factors on clinical manifestations. RESULTS Two novel genetic risks, HLA-DQA1*06:01 and HLA-DQB1*06:09, were significantly associated with anti-MDA5+ DM in both the discovery and validation cohorts. HLA-DQA1*06:01 was particularly prevalent in anti-MDA5+ DM (20.4%) compared with anti-MDA5⁻ DM (6.69%) and non-DM rheumatic disease (5.93%). Besides, the strongest associated amino acid was HLA-DQα1:69 (P = 3.27 × 10-11), and 1 SNP in the ARHGAP22 gene (rs76208937) showed suggestive significance (P = 7.99 × 10-6). In addition, HLA-DQA1*06:01 was linked to acute rapidly progressive interstitial lung disease (P < .001), elevated levels of lactate dehydrogenase (P = .026), and death (P = .049) in patients with anti-MDA5+ DM. CONCLUSIONS HLA-DQA1*06:01 is a new genetic and prognostic factor for anti-MDA5+ DM, potentially serving as a biomarker for early diagnosis and intervention.
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Affiliation(s)
- Xinzhuang Yang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, State Key Laboratory of Complex Severe and Rare Diseases, Ministry of Science & Technology, Beijing, China; Center for Bioinformatics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine & Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chen Yu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, State Key Laboratory of Complex Severe and Rare Diseases, Ministry of Science & Technology, Beijing, China
| | - Xiuling Zhang
- Department of Rheumatology and Immunology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Chanyuan Wu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, State Key Laboratory of Complex Severe and Rare Diseases, Ministry of Science & Technology, Beijing, China
| | - Zhao Peng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, State Key Laboratory of Complex Severe and Rare Diseases, Ministry of Science & Technology, Beijing, China
| | - Yixuan Gai
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, State Key Laboratory of Complex Severe and Rare Diseases, Ministry of Science & Technology, Beijing, China
| | - Jinmin Peng
- Medical Intensive Care Unit, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Shuang Zhou
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, State Key Laboratory of Complex Severe and Rare Diseases, Ministry of Science & Technology, Beijing, China
| | - Lan Song
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Hui Huang
- Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Dong Xu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, State Key Laboratory of Complex Severe and Rare Diseases, Ministry of Science & Technology, Beijing, China
| | - Jiuliang Zhao
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, State Key Laboratory of Complex Severe and Rare Diseases, Ministry of Science & Technology, Beijing, China
| | - Xinping Tian
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, State Key Laboratory of Complex Severe and Rare Diseases, Ministry of Science & Technology, Beijing, China
| | - Xinwang Duan
- Department of Rheumatology and Immunology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, State Key Laboratory of Complex Severe and Rare Diseases, Ministry of Science & Technology, Beijing, China
| | - Mengtao Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, State Key Laboratory of Complex Severe and Rare Diseases, Ministry of Science & Technology, Beijing, China.
| | - Qian Wang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Science & Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, State Key Laboratory of Complex Severe and Rare Diseases, Ministry of Science & Technology, Beijing, China.
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13
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Okuno K, Masago A, Himejima A, Takahashi K. The efficacy of occlusal appliance with a moisturizing gel pocket on sleep quality in patients with nocturnal xerostomia: A case series. J Prosthodont Res 2025; 69:308-312. [PMID: 39384398 DOI: 10.2186/jpr.jpr_d_24_00127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/11/2024]
Abstract
PATIENTS A case series of five patients (mean age, 77.0 years) with complaints of nocturnal xerostomia were subjected to occlusal appliance treatment with a reservoir of moisturizing gel during the night. An occlusal appliance covers the dental arch and hard palate, providing space in the midline of the hard palate to hold the moisturizing gel. Sleepiness was assessed using the Epworth Sleepiness Scale (ESS), and sleep quality was assessed using the Japanese version of the Pittsburgh Sleep Questionnaire (PSQI-J) before and after treatment. The total PSQI-J scores decreased in all patients after treatment. The ESS score, sleep time, and sleep efficiency improved or remained unchanged and none of the patients' symptoms worsened. DISCUSSION This study demonstrated the efficacy of occlusal appliance treatment in patients with dry mouth in improving self-reported sleep quality. Patients included those with nocturnal xerostomia and poor sleep quality on the PSQI-J. Treatment with xerostomia resulted in improved sleep quality, as assessed by the decrease in PSQI-J scores. CONCLUSIONS This case series suggests that sleep quality may be worse in patients with xerostomia, and that treatment for nocturnal xerostomia using occlusal appliances may improve sleep quality.
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Affiliation(s)
- Kentaro Okuno
- Department of Geriatric Dentistry, Osaka Dental University, Hirakata, Japan
- Center for Dental Sleep Medicine, Osaka Dental University Hospital, Osaka, Japan
| | - Ayako Masago
- Department of Geriatric Dentistry, Osaka Dental University, Hirakata, Japan
| | - Akio Himejima
- First Department of Oral and Maxillofacial Surgery, Osaka Dental University, Osaka, Japan
| | - Kazuya Takahashi
- Department of Geriatric Dentistry, Osaka Dental University, Hirakata, Japan
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Liao K, Li N, Bonin J, Koelmeyer R, Kent J, Pellicano R, De Silva T, Yap K, Golder V, Kitching AR, Morand EF, Hoi A. The implication of anti-Ro60 with or without anti-Ro52 antibody in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2025; 64:1923-1929. [PMID: 39141489 PMCID: PMC11962896 DOI: 10.1093/rheumatology/keae362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 04/17/2024] [Accepted: 07/08/2024] [Indexed: 08/16/2024] Open
Abstract
OBJECTIVES Anti-Ro60 and anti-Ro52 autoantibodies are frequently used as diagnostic biomarkers for Sjögren's disease, but their clinical significance in systemic lupus erythematosus (SLE) is not well characterized. METHODS Patients fulfilling SLE classification criteria were studied according to their anti-Ro status. We defined Ro positivity (Ro+) as those who have either anti-Ro60 or anti-Ro52 positivity. Patient characteristics and disease outcomes, including High Disease Activity Status (HDAS) defined as an ever attainment of SLEDAI2K ≥10, adjusted mean SLEDAI (AMS), and time-adjusted mean clinical SLEDAI (excluding serologic activities) were compared using linear or logistic regressions. Furthermore, isolated or dual positivity of anti-Ro60 and anti-Ro52 were studied. RESULTS Out of 409 patients, 47.2% were Ro+. Ro+ patients were predominantly Asian, had positive dsDNA and hypocomplementemia. They showed a higher likelihood of HDAS (OR 1.65, 95% CI 1.10-2.48, P = 0.015), AMS >4 (OR 1.84, 1.18-2.88, P = 0.007) and more frequent use of glucocorticoids (OR 1.87, 1.16-3.03, P = 0.011) and immunosuppressants (OR 2.0, 1.26-3.17, P = 0.003). Additionally, 24.4% of Ro+ patients experienced sicca symptoms, and hypergammaglobulinemia was significantly more common. Multivariate analysis confirmed that Asian ethnicity, severe flares, AMS, hypocomplementemia, rheumatoid factor, proteinuria, leucopenia and sicca symptoms were significantly linked to Ro positivity. CONCLUSION Anti-Ro positivity is associated with higher disease activity and increased treatment needs. Ro positivity correlates with laboratory abnormalities such as hypocomplementemia and leucopenia. These findings highlight the importance of anti-Ro60/Ro52 testing in the clinical evaluation of SLE.
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Affiliation(s)
- Katie Liao
- Department of Rheumatology, Monash Health, Clayton, VIC, Australia
| | - Ning Li
- Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, VIC, Australia
| | - Julie Bonin
- Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, VIC, Australia
| | - Rachel Koelmeyer
- Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, VIC, Australia
| | - Joanna Kent
- Department of Nephrology, Monash Health, Clayton, VIC, Australia
| | | | | | - Kristy Yap
- Department of Rheumatology, Monash Health, Clayton, VIC, Australia
| | - Vera Golder
- Department of Rheumatology, Monash Health, Clayton, VIC, Australia
- Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, VIC, Australia
| | - A Richard Kitching
- Department of Rheumatology, Monash Health, Clayton, VIC, Australia
- Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, VIC, Australia
| | - Eric F Morand
- Department of Rheumatology, Monash Health, Clayton, VIC, Australia
- Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, VIC, Australia
| | - Alberta Hoi
- Department of Rheumatology, Monash Health, Clayton, VIC, Australia
- Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, VIC, Australia
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Islam MS, Mamtaz Uddin Ahmed Q, Ahmed F, Uddin MA, Naher N. Sjogren's Syndrome Presenting With Proximal Myopathy Due to Osteomalacia Complicating Renal Tubular Acidosis: A Case Report. Cureus 2025; 17:e82206. [PMID: 40370894 PMCID: PMC12075618 DOI: 10.7759/cureus.82206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/13/2025] [Indexed: 05/16/2025] Open
Abstract
Primary Sjögren's syndrome (pSS) is typically associated with dryness of the eyes and mouth, but it can also involve other organs, including the lungs, kidneys, nervous system, and joints. Among its less common manifestations is distal renal tubular acidosis (dRTA), which can lead to metabolic acidosis, hypokalemia, and bone-related complications due to chronic acid-base imbalance. We report the case of a 42-year-old woman with a four-year history of recurrent hypokalemic quadriparesis, who recently developed progressive difficulty walking over the past two months, severely limiting her mobility. Laboratory investigations revealed a normal anion gap metabolic acidosis and elevated urine pH, consistent with dRTA. Further evaluation confirmed a diagnosis of pSS with objective evidence of glandular involvement. Imaging and biochemical findings supported the presence of osteomalacia secondary to dRTA. This case highlights a rare and often overlooked complication of pSS. Timely diagnosis and appropriate management are crucial to preventing long-term disability and improving patient outcomes.
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Affiliation(s)
- Mohammad Syedul Islam
- Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
| | | | - Farzana Ahmed
- Department of Pediatrics, Marks Medical College and Hospital, Dhaka, BGD
| | - Md Ashraf Uddin
- Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
| | - Naznin Naher
- Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
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Hakbilen S, Tezcan D, Onmaz DE, Yılmaz S, Körez MK, Ünlü A. The role of CXCL9, CXCL10, and CXCL13 chemokines in patients with Sjögren's syndrome. Clin Rheumatol 2025; 44:1635-1642. [PMID: 39992599 DOI: 10.1007/s10067-025-07367-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 01/14/2025] [Accepted: 02/13/2025] [Indexed: 02/26/2025]
Abstract
INTRODUCTION Sjögren's syndrome (SS) is a chronic, systemic, and autoimmune disease characterized by lymphocytic infiltration of all exocrine glands, primarily the lacrimal and salivary glands. Chemokines play a key role in many inflammatory diseases. They play a fundamental role in recruitment, transport, and activation of immune cells. This study aimed to investigate the role of CXCL9, CXCL10, and CXCL13 chemokines in primary SS patients. METHOD The study included 62 SS patients and 68 individuals without known systemic or rheumatological disease. CXCL9, CXCL10, and CXCL13 levels were analyzed in both groups using ELISA test kits and compared. The mean age of SS and healthy controls (HC) were similar. White blood cell neutrophil and lymphocyte values were found significantly lower in the SS compared to the HC; ESR value was higher in SS. Other hemogram parameters such as hemoglobin, platelets, monocytes, and CRP did not show a significant difference. CXCL10 levels were found to be significantly higher in SS compared to HC. CXCL13 level was significantly lower in SS. However, there was no statistically significant difference in CXCL9 serum between SS and HC. There was a negative correlation between serum CXCL9 level and lymphocyte and there was also a positive correlation between CXCL13 serum level and leukocyte. CONCLUSION CXCL10 chemokine may serve as a potential biomarker for primary SS and it may also be a new therapeutic target. Key Points • Chemokines play a key role in Sjögren's syndrome. • CXCL10 may serve as a potential biomarker for primary SS.
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Affiliation(s)
- Selda Hakbilen
- Division of Rheumatology, Faculty of Medicine, Selcuk University, Konya, Turkey
| | - Dilek Tezcan
- Department of Internal Medicine, Division of Rheumatology, Gülhane Faculty of Medicine, University of Health Sciences Turkey, Ankara, Turkey.
| | - Duygu Eryavuz Onmaz
- Division of Biochemistry, Faculty of Medicine, Selcuk University, Konya, Turkey
| | - Sema Yılmaz
- Division of Rheumatology, Faculty of Medicine, Selcuk University, Konya, Turkey
| | - Muslu Kazım Körez
- Division of Biostatistics, Faculty of Medicine, Selcuk University, Konya, Turkey
| | - Ali Ünlü
- Division of Biochemistry, Faculty of Medicine, Selcuk University, Konya, Turkey
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17
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Al-Ezzi MY, Khan KS, Tappuni AR. Quality of Life and Mental Health Well-Being in Sjögren's Disease in the UK: A Cross-Sectional Comparative Analysis. J Clin Med 2025; 14:1939. [PMID: 40142745 PMCID: PMC11943019 DOI: 10.3390/jcm14061939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Revised: 03/08/2025] [Accepted: 03/11/2025] [Indexed: 03/28/2025] Open
Abstract
Objectives: We aimed to evaluate the quality of life (QoL), oral health-related quality of life (OHRQoL), and mental health well-being in female patients diagnosed with Sjögren's Disease compared with healthy controls. Methods: An ethically approved cross-sectional study was carried out on 65 female patients with a confirmed diagnosis of Sjögren's Disease according to the American European Association Consensus Group Criteria and 61 sex-matched healthy volunteers. The World Health Organization Quality of Life-BREF, Oral Health Impact Profile-14, and Hospital Anxiety and Depression Scale were used to evaluate the general and oral health-related QoL (OHRQoL) and the mental health well-being of the participants. Results: The general QoL was lower in the patients' group (p < 0.05) compared with the control group in all four domains (physical, psychological, social, and environment). The OHRQoL was significantly reduced in the patients' group, who were more anxious (58.5%, n = 38/65) and four times more depressed (32.3%, n = 21/65) compared with healthy volunteers (anxiety = 21%, n = 13/61; depression = 8.2%, n = 5/61). Conclusions: This study concludes that Sjögren's Disease negatively affects QoL and mental well-being. Therefore, addressing these aspects in patients' management is crucial to helping individuals cope with the disease's burden and ultimately enhancing their overall life experience.
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Affiliation(s)
- Minan Y. Al-Ezzi
- Bristol Dental School, Faculty of Health and Life Sciences, University of Bristol, Bristol BS2 0PT, UK;
- College of Medicine and Dentistry, Ulster University, Birmingham B4 6BN, UK
| | - Khalid S. Khan
- Department of Preventive Medicine and Public Health, Faculty of Medicine, University of Granada, 18016 Granada, Spain;
| | - Anwar R. Tappuni
- Faculty of Medicine and Dentistry, Queen Mary University of London, London E1 1BB, UK
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18
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Kupa LVK, Medeiros-Ribeiro AC, Aikawa NE, Pasoto SG, Borba EF, Assad APL, Saad CGS, Yuki EFN, Seguro LPC, Andrade D, Shinjo SK, Sampaio-Barros PD, Shimabuco AY, Moraes JCB, Sampaio VS, Giardini HAM, Silva CAA, Bonfá E. Disease Safety, Immunogenicity, and Efficacy of Recombinant Herpes Zoster Vaccine (RZV or Shingrix) in Autoimmune Rheumatic Diseases: Launching a Randomized Phase 4 Study. J Clin Rheumatol 2025:00124743-990000000-00326. [PMID: 40036115 DOI: 10.1097/rhu.0000000000002216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2025]
Abstract
BACKGROUND Patients with autoimmune rheumatic diseases (ARDs) are at an increased risk for herpes zoster (HZ). Vaccination is recommended for this population. OBJECTIVE The aim of this study was to evaluate the safety of vaccination with the recombinant zoster vaccine (Shingrix) in ARD patients, humoral immunogenicity (HI), cellular immunogenicity (CI), and the incidence of HZ. METHODS This randomized, double-blind, placebo-controlled phase 4 study involves 1180 ARD patients and a control group (CG) of 393 balanced healthy individuals, aged ≥50 years. ARD patients will be randomly assigned in a blinded manner (1:1 ratio) to 2 groups: vaccine or placebo (on days 0 and 42), administered intramuscularly. Outcomes will be assessed at baseline, 6 weeks, and 12 weeks after vaccination, including disease activity (using specific disease activity scores), HI, and CI. Adverse events will be assessed using a standardized questionnaire after each vaccine dose. Incident HZ cases will be monitored throughout the study. One year following the second dose, the persistence of HI and CI will be evaluated in both ARD patients and CG. HI and CI will be assessed using serum concentrations of anti-gE antibodies and the frequencies of gE-specific CD4+ T cells, respectively. Comparisons of anti-gE titers between ARD patients and CG at different time points will be analyzed using 2-way repeated-measures analysis of variance. Multiple regression analysis will be conducted, with a positive immune response as the dependent variable, and variables with p < 0.2 from univariate analysis as independent variables. CONCLUSIONS This large trial addresses a critical gap by examining disease safety, efficacy, adverse effects, and immunogenicity, considering the impact of diverse therapies following recombinant zoster vaccine administration in ARD patients.
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Affiliation(s)
- Leonard V K Kupa
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Ana Cristina Medeiros-Ribeiro
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Sandra G Pasoto
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Eduardo F Borba
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Ana Paula L Assad
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Carla G S Saad
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Emily F N Yuki
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Luciana P C Seguro
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Danieli Andrade
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Samuel K Shinjo
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Percival D Sampaio-Barros
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Andrea Y Shimabuco
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Júlio Cesar B Moraes
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Henrique A M Giardini
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Clovis A A Silva
- Pediatric Rheumatology Unit, Instituto da Criança e do Adolescente, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Eloisa Bonfá
- From the Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
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19
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Rusinovich Lovgach O, Plaza Z, Fernández Castro M, Rosas J, Martínez-Taboada V, Olivé A, Menor Almagro R, Serrano Benavente B, Font-Urgelles J, Garcia-Aparicio A, Manrique-Arija S, Garcia-Vadillo A, Lopez-Gonzalez R, Narvaez García J, Rodriguez-Lozano MB, Galisteo C, Gonzalez-Martin JJ, Vela-Casasempere P, Bohorquez C, Erausquin C, Paredes-Romero MB, Riancho-Zarrabeitia L, Melchor Diaz S, Pego-Reigosa JM, Heredia S, Moriano C, Blazquez Cañamero MA, Estrada P, Judez E, Belzunegui Otano J, Ramos Giráldez C, Domínguez-Álvaro M, Sánchez Alonso F, Andréu Sánchez JL. Mortality in Patients With Sjögren Disease: A Prospective Cohort Study Identifying Key Predictors. J Rheumatol 2025; 52:257-262. [PMID: 39814434 DOI: 10.3899/jrheum.2024-1033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/09/2024] [Indexed: 01/18/2025]
Abstract
OBJECTIVE We aimed to quantify the mortality risk in a large, well-characterized cohort of patients with Sjögren disease (SjD) and to identify independent predictors of mortality in this population. METHODS We included 314 patients diagnosed with SjD according to the 2002 American-European Consensus Group criteria from a prospective, multicenter SjögrenSER Prospective cohort. Detailed data on systemic manifestations, serological markers, disease activity, and mortality were collected after a median of 9.5 (IQR 9.2-9.9) years of follow-up. The primary outcome was overall mortality, and secondary analyses aimed to identify independent predictors of mortality using Cox proportional hazards models. Standardized mortality ratios were calculated by comparing the observed deaths in the SjD cohort to the expected deaths in an age- and sex-matched general population. RESULTS The study identified a 70% increased mortality risk in the SjD cohort compared to the general population, with a standard mortality ratio of 1.7. Infections (35.7%), malignancies (23.8%), and cardiovascular disease (CVD; 7.1%) were the most common causes of death. Multivariate analysis revealed that older age (HR 1.11/year, 95% CI 1.07-1.15), C4 hypocomplementemia (HR 3.75, 95% CI 1.55-9.06), elevated erythrocyte sedimentation rate (ESR; HR 1.01, 95% CI 1.00-1.03), history of heart failure (HR 4.24, 95% CI 1.02-17.58), and pulmonary involvement (HR 3.31, 95% CI 1.39-7.88) were independent predictors of mortality. CONCLUSION This study found a significantly increased mortality risk in SjD, with infections, malignancies, and CVD as leading causes of death. Independent predictors of mortality include advanced age, C4 hypocomplementemia, elevated ESR, heart failure, and pulmonary involvement, underscoring the need for proactive, individualized management.
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Affiliation(s)
- Olga Rusinovich Lovgach
- O. Rusinovich Lovgach, MD, M. Fernández Castro, PhD, J.L. Andréu Sánchez, PhD, Rheumatology Department, Puerta de Hierro Majadahonda University Hospital, Madrid;
| | - Zulema Plaza
- Z. Plaza, PhD, M. Domínguez-Álvaro, PhD, F. Sánchez Alonso, MSc, Research Unit, Spanish Society of Rheumatology, Madrid
| | - Mónica Fernández Castro
- O. Rusinovich Lovgach, MD, M. Fernández Castro, PhD, J.L. Andréu Sánchez, PhD, Rheumatology Department, Puerta de Hierro Majadahonda University Hospital, Madrid
| | - José Rosas
- J. Rosas, PhD, Rheumatology Department, Marina Baixa de la Vila Joiosa Hospital, Alicante
| | - Victor Martínez-Taboada
- V. Martínez-Taboada, PhD, Rheumatology Department, Marqués de Valdecilla University Hospital, Departament of Medicine y Psychiatry, University of Cantabria, Santander
| | - Alejandro Olivé
- A. Olivé, PhD, J. Font-Urgelles, MD, Rheumatology Department, Hospital Universitario Germans Trías i Pujol Badalona, Barcelona
| | - Raul Menor Almagro
- R. Menor Almagro, MD, Rheumatology Department, H. General Universitario Jerez de la Frontera, Cádiz
| | | | - Judit Font-Urgelles
- A. Olivé, PhD, J. Font-Urgelles, MD, Rheumatology Department, Hospital Universitario Germans Trías i Pujol Badalona, Barcelona
| | - Angel Garcia-Aparicio
- A. Garcia-Aparicio, PhD, Rheumatology Department, Hospital Universitario de Toledo, Toledo
| | - Sara Manrique-Arija
- S. Manrique-Arija, PhD, Rheumatology Department, Málaga Regional Hospital, Institute of Biomedical Investigation, Department of Medicine and Dermatology, University of Málaga, Málaga
| | - Alberto Garcia-Vadillo
- A. Garcia-Vadillo, MD, Rheumatology Department, Hospital Universitario La Princesa, and Departamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa, Madrid
| | - Ruth Lopez-Gonzalez
- R. Lopez-Gonzalez, PhD, Rheumatology Department, Zamora Health Complex, Salamanca University, Salamanca
| | - Javier Narvaez García
- J. Narvaez García, PhD, Rheumatology Department, Bellvitge University Hospital, Bellvitge Biomedical Research Institute, Barcelona
| | | | - Carlos Galisteo
- C. Galisteo, MD, Rheumatology Department, Hospital Parc Taulí, Sabadel
| | | | - Paloma Vela-Casasempere
- P. Vela-Casasempere, PhD, Rheumatology Department, General University Hospital Dr. Balmis, Institute for Health and Biomedical Research (ISABIAL), Alicante, and Miguel Hernández University, Elche
| | - Cristina Bohorquez
- C. Bohorquez, MD, Rheumatology Department, Príncipe de Asturias University Hospital, Alcalá de Henares, and Departamento de Medicina, Alcalá University, Madrid
| | - Celia Erausquin
- C. Erausquin, PhD, Rheumatology Department, Dr Negrin University Hospital, Las Palmas
| | - María Beatriz Paredes-Romero
- M.B. Paredes-Romero, MD, Rheumatology Department, Infanta Sofía, University Hospital, San Sebastián de los Reyes, Madrid
| | - Leyre Riancho-Zarrabeitia
- L. Riancho-Zarrabeitia, PhD, Rheumatology Department, Sierrallana Hospital, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Santander
| | - Sheila Melchor Diaz
- S. Melchor Diaz, PhD, Rheumatology Department, 12 de Octubre University Hospital, Madrid
| | - Jose Maria Pego-Reigosa
- J.M. Pego-Reigosa, PhD, Rheumatology Department, University Hospital of Vigo, IRIDIS-VIGO Group, Vigo
| | - Sergio Heredia
- S. Heredia, MD, Rheumatology Department, P. Estrada, PhD, Complex Hospitalari Universitari Moisès Broggi, Barcelona
| | - Clara Moriano
- C. Moriano, MD, Rheumatology Department, León University Hospital, León
| | | | - Paula Estrada
- S. Heredia, MD, Rheumatology Department, P. Estrada, PhD, Complex Hospitalari Universitari Moisès Broggi, Barcelona
| | - Enrique Judez
- E. Judez, MD, Rheumatology Department, Albacete University Hospital, Albacete
| | | | | | - Marta Domínguez-Álvaro
- Z. Plaza, PhD, M. Domínguez-Álvaro, PhD, F. Sánchez Alonso, MSc, Research Unit, Spanish Society of Rheumatology, Madrid
| | - Fernando Sánchez Alonso
- Z. Plaza, PhD, M. Domínguez-Álvaro, PhD, F. Sánchez Alonso, MSc, Research Unit, Spanish Society of Rheumatology, Madrid
| | - José Luis Andréu Sánchez
- O. Rusinovich Lovgach, MD, M. Fernández Castro, PhD, J.L. Andréu Sánchez, PhD, Rheumatology Department, Puerta de Hierro Majadahonda University Hospital, Madrid
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20
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Liang Y, Zhang Z, Li J, Yang Z. Association of increased serum I-309 with phenotypes, disease activity, and cytokine pattern in primary Sjögren's syndrome. Clin Rheumatol 2025; 44:1237-1243. [PMID: 39849259 DOI: 10.1007/s10067-025-07327-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 12/23/2024] [Accepted: 01/09/2025] [Indexed: 01/25/2025]
Abstract
The aim of this study was to determine serum I-309 levels in primary Sjögren's syndrome (pSS) patients, as well as the association with disease phenotype, systemic activity, and T helper cell-related cytokines. A total of 58 pSS patients and 30 healthy controls (HC) were enrolled in this study. The concentrations of serum I-309, interleukin-4 (IL-4), IL-6, IL-9, IL-13, IL-17, IL-22, IL-23, tumor-necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IFN-α, and IFN-β were measured with multiplex immunoassay. The relationships between I-309 and various clinical and laboratory variables were analyzed. The serum concentrations of I-309 were significantly increased (median, IQR, 14.24, 10.99--20.35, pg/ml) in pSS patients compared with HC (median, IQR, 8.27, 6.74--9.62, pg/ml) (P < 0.001). Serum I-309 is increased in pSS, and may be associated with systemic inflammation, Th1-, Th17,- and Th9 cells, type Key Points • Serum I-309 levels are increased in pSS patients. • Increased I-309 may be associated with systemic rather than local manifestations in pSS. • Increased I-309 may be associated with Th1, Th17 and Th9 other than Th2 in pSS. • There may be close relationships between I-309 and type land type II IFNs in pSS.
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Affiliation(s)
- Yan Liang
- Department of Laboratory Medicine, Changzheng Hospital, Naval Medical University, Shanghai, China.
| | - Zhiyu Zhang
- Health Management Center, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Jie Li
- Department of Laboratory Medicine, Huangyan Hospital of Wenzhou Medical University, Taizhou First People's Hospital, Taizhou, Zhejiang, China
| | - Zaixing Yang
- Department of Laboratory Medicine, Huangyan Hospital of Wenzhou Medical University, Taizhou First People's Hospital, Taizhou, Zhejiang, China.
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21
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Galindo-Feria AS, Lodin K, Horuluoglu B, Sarrafzadeh-Zargar S, Wigren E, Gräslund S, Danielsson O, Wahren-Herlenius M, Dastmalchi M, Lundberg IE. Anti-FHL1 autoantibodies in adult patients with myositis: a longitudinal follow-up analysis. Rheumatology (Oxford) 2025; 64:1482-1492. [PMID: 38833674 PMCID: PMC11879316 DOI: 10.1093/rheumatology/keae317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 04/15/2024] [Accepted: 05/21/2024] [Indexed: 06/06/2024] Open
Abstract
OBJECTIVES To determine prevalence and clinical associations of anti-Four-and-a-half-LIM-domain 1 (FHL1) autoantibodies in patients with idiopathic inflammatory myopathies (IIM) and to evaluate autoantibody levels over time. METHODS Sera at the time of diagnosis from patients with IIM (n = 449), autoimmune disease controls (DC, n = 130), neuromuscular diseases (NMDs, n = 16) and healthy controls (HC, n = 100) were analysed for anti-FHL1 autoantibodies by enzyme-linked immunosorbent assay (ELISA). Patients with IIM FHL1+ and FHL1- were included in a longitudinal analysis. Serum levels were correlated to disease activity. RESULTS Autoantibodies to FHL1 were more frequent in patients with IIM (122/449, 27%) compared with DC (autoimmune DC and NMD, 13/146, 9%, P < 0.001) and HC (3/100.3%, P < 0.001). Anti-FHL1 levels were higher in IIM [median (IQR)=0.62 (0.15-1.04)] in comparison with DC [0.22 (0.08-0.58)], HC [0.35 (0.23-0.47)] and NMD [0.48 (0.36-0.80)] P < 0.001. Anti-FHL1+ patients with IIM were younger at the time of diagnosis compared with the anti-FHL1- group (P = 0.05) and were seronegative for other autoantibodies in 25%.In the first follow-up, anti-FHL1+ sample 20/33 (60%) positive at baseline had turned negative for anti-FHL1 autoantibodies. Anti-FHL1 autoantibodies rarely appeared after initiating treatment. Anti-FHL1 autoantibody levels correlated with CK (r = 0.62, P= 0.01), disease activity measured using the Myositis Disease Activity Assessment Tool (MYOACT) (n = 14, P = 0.004) and inversely with Manual Muscle Test-8 (r = -0.59, P = 0.02) at baseline. CONCLUSION Anti-FHL1 autoantibodies were present in 27% of patients with IIM; of these, 25% were negative for other autoantibodies. Other autoimmune diseases had lower frequencies and levels. Anti-FHL1 levels often decreased with immunosuppressive treatment, correlated with disease activity measures at diagnosis and rarely appeared after start of treatment.
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Affiliation(s)
- Angeles S Galindo-Feria
- Department of Medicine, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden
- Center for Molecular Medicine, Division for Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
- Department of Gastro, Dermatology and Rheumatology, Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden
| | - Karin Lodin
- Department of Medicine, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden
- Center for Molecular Medicine, Division for Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
- Department of Gastro, Dermatology and Rheumatology, Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden
| | - Begum Horuluoglu
- Department of Medicine, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden
- Center for Molecular Medicine, Division for Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
| | - Sepehr Sarrafzadeh-Zargar
- Department of Medicine, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden
- Center for Molecular Medicine, Division for Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
| | - Edvard Wigren
- Department of Medicine, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden
- Department of Medicine, Division of Rheumatology, Structural Genomics Consortium, Karolinska Institutet, Stockholm, Sweden
| | - Susanne Gräslund
- Department of Medicine, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden
- Department of Medicine, Division of Rheumatology, Structural Genomics Consortium, Karolinska Institutet, Stockholm, Sweden
| | - Olof Danielsson
- Department of Biomedical and Clinical Sciences, Division of Neurology, Faculty of Medicine and Health Sciences, Linkoping University, Linkoping, Sweden
| | - Marie Wahren-Herlenius
- Department of Medicine, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden
- Center for Molecular Medicine, Division for Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
- Department of Clinical Science, Broegelmanns Research Laboratory, University of Bergen, Bergen, Norway
| | - Maryam Dastmalchi
- Department of Medicine, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden
- Center for Molecular Medicine, Division for Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
- Department of Gastro, Dermatology and Rheumatology, Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden
| | - Ingrid E Lundberg
- Department of Medicine, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden
- Center for Molecular Medicine, Division for Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
- Department of Gastro, Dermatology and Rheumatology, Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden
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22
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Lee KA, Jeon H, Kim HS, Choi K, Seo GH. Increased risk of dementia in patients with primary Sjogren's syndrome: a nationwide population-based cohort study. Korean J Intern Med 2025; 40:330-338. [PMID: 39987901 PMCID: PMC11938687 DOI: 10.3904/kjim.2023.536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 06/13/2024] [Accepted: 07/03/2024] [Indexed: 02/25/2025] Open
Abstract
BACKGROUND/AIMS This nationwide cohort study aimed to evaluate (1) whether primary Sjogren's syndrome (pSS) can contribute to the development of dementia and (2) whether the use of hydroxychloroquine (HCQ) can decrease the incidence of dementia in patients with pSS using the Health Insurance Review and Assessment database. METHODS We established a cohort between 2008 and 2020 of 20,160 patients with pSS without a history of dementia. The control group comprised sex- and age-matched individuals with no history of autoimmune disease or dementia. Cox proportional hazard analyses were performed to identify the association between pSS and dementia development. We also assessed the hazard ratio (HR) of dementia in early users of HCQ (within 180 days of the diagnosis of pSS) compared to non-users, adjusted for age, sex, and comorbidities. RESULTS The incidence of dementia was 0.68 (95% CI 0.64-0.72) cases per 100 person-years in pSS, and it was 0.58 (0.56-0.60) in the controls. The adjusted HR (aHR) of developing dementia was 1.16 (1.09-1.25) times greater in the pSS group than in the controls. The risk of dementia did not increase in HCQ users (aHR 1.07 [0.94-1.21]), but HCQ non-users had a 1.22 (1.12-1.33) higher risk of developing dementia than the matched controls. The use of HCQ lowered the risk of dementia in comparison with non-users in patients with pSS (aHR 0.82 [0.71-0.94]). CONCLUSION Our results suggest that pSS is associated with an increased risk of dementia. HCQ may prevent dementia in patients with pSS.
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Affiliation(s)
- Kyung-Ann Lee
- Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University School of Medicine, Seoul,
Korea
| | - Hyeji Jeon
- Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University School of Medicine, Seoul,
Korea
| | - Hyun-Sook Kim
- Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University School of Medicine, Seoul,
Korea
| | - Kyomin Choi
- Department of Neurology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University School of Medicine, Cheonan,
Korea
| | - Gi Hyeon Seo
- Health Insurance Review and Assessment Service, Wonju,
Korea
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Okamoto M, Yoshida M, Tsuga K, Matsuo K, Ikebe K, Ueda T, Minakuchi S. Associations of sex, age, and number of remaining teeth with performance on oral hypofunction tests. Gerodontology 2025; 42:52-60. [PMID: 38874012 DOI: 10.1111/ger.12770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/03/2024] [Indexed: 06/15/2024]
Abstract
INTRODUCTION Oral hypofunction comprises seven aspects of oral condition, including oral hygiene, oral dryness, bite strength, tongue-lip motor function, tongue pressure, masticatory function, and swallowing function. Each of these seven has a single diagnostic criterion; however, the use of a single indicator without consideration of sex, age, or other factors is controversial. The purpose of this study was to evaluate the association between the oral hypofunction test and sex, age, and number of remaining teeth. METHODS The study was conducted at 12 facilities by the members of the Japanese Society of Geriatric Dentistry during April to December 2019. The participants comprised 181 healthy older adults aged 65 years and over (56.9% female; age range 65-95 years) who regularly visited these facilities. All tests of oral function and oral status available in Japan were performed on the participants, and the association between these tests and sex, age, and number of remaining teeth was examined. RESULTS Sex differences were observed in masticatory function, bite force, lip closure force, jaw-opening force, oral diadochokinesis "ka," and tongue coating index (p < .05). In men, age was weakly (r = 0.20-0.40) associated with masticatory function, jaw-opening force, maximum tongue pressure, oral diadochokinesis, and swallowing function. In women, the number of remaining teeth, masticatory function, jaw-opening force, and oral diadochokinesis "ta" and "ka" was also weakly associated with age. CONCLUSIONS Performance on the oral hypofunction test differs by sex, age, and number of remaining teeth. This means that the current single criterion for evaluation requires caution in its interpretation.
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Affiliation(s)
- Mieko Okamoto
- Department of Dentistry and Oral-Maxillofacial Surgery, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Mitsuyoshi Yoshida
- Department of Dentistry and Oral-Maxillofacial Surgery, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Kazuhiro Tsuga
- Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Koichiro Matsuo
- Department of Oral Health Sciences for Community Welfare, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kazunori Ikebe
- Department of Removable Prosthodontics and Gerodontology, Graduate School of Dentistry, Osaka University, Osaka, Japan
| | - Takayuki Ueda
- Department of Removable Prosthodontics and Gerodontology, Tokyo Dental College, Tokyo, Japan
| | - Shunsuke Minakuchi
- Department of Gerodontology and Oral Rehabilitation, Department of Gerontology and Gerodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
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Wu J, Feng R, Wang R, He J. Impact of disease duration on systemic clinical profile in Sjogren's syndrome. Arthritis Res Ther 2025; 27:39. [PMID: 39994738 PMCID: PMC11849184 DOI: 10.1186/s13075-025-03490-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 01/27/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Primary Sjogren's Syndrome (pSS) is a systemic autoimmune disorder characterized by lymphocyte infiltration of the exocrine glands. Disease duration plays a pivotal role in evaluating the development of SS. In this study, we aimed to clarify the clinical manifestations of pSS across various stages of its progression, thereby offering critical insights for early diagnosis and targeted management strategies for Sjogren's Syndrome. METHODS We conducted a retrospective analysis involving 3,978 patients with primary Sjogren's Syndrome (mean [SD] age: 53.1[24] years) from Peking University People's Hospital between January 2015 and December 2022. We classified patients into five distinct groups based on the duration of the syndrome: T0 (≤ 1 year), T1 (> 1 year, ≤ 5 years), T2 (> 5 years, ≤ 10 years), T3 (> 10 years, ≤ 20 years), and T4 (> 20 years). RESULTS We observed a statistically significant increase in the percentage of pSS patients with white blood cell (WBC) decrease, specifically: T0 (9.23%), T1 (15.40%), T2 (22.62%), T3 (20.22%), T4 (26.45%). The decreases in hemoglobin (HGB) and platelet (PLT) were also robustly associated with extended disease duration (p < 0.0001). Simultaneously, systemic involvements aggravated with disease progression as incidence rates of skin, joint, lung, and nervous system were strikingly increased in each group. The findings also indicated that patients with long-term pSS exhibit a higher likelihood of developing comorbid conditions, such as diabetes and tumors. In summary, disease duration serves as a crucial determinant for the prognosis of patients with pSS. CONCLUSIONS Therefore, early identification of symptoms and initiation of therapies are imperative for mitigating the risk of significant complications in pSS patients.
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Affiliation(s)
- Jingchun Wu
- Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing, 100044, China
| | - Ruiling Feng
- Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing, 100044, China
| | - Ruoyi Wang
- Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing, 100044, China
| | - Jing He
- Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing, 100044, China.
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Hanaoka H, Kikuchi J, Hiramoto K, Akiyama M, Saito S, Kondo Y, Azegami T, Kaneko Y. Dapagliflozin for rheumatic musculoskeletal disease in patients with chronic kidney disease. Mod Rheumatol 2025; 35:345-351. [PMID: 39401147 DOI: 10.1093/mr/roae090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 09/18/2024] [Indexed: 02/22/2025]
Abstract
OBJECTIVES To elucidate the effectiveness of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, on renal function in patients with rheumatic musculoskeletal diseases complicated by chronic kidney disease (CKD). METHODS We conducted a retrospective analysis of patients with rheumatic musculoskeletal disease and chronic kidney disease who were treated with dapagliflozin for more than a year. The good response was defined as an improvement in the estimated glomerular filtration rate slope per year after dapagliflozin treatment compared to that before treatment. Additionally, we investigated the response rate and its predictive factors. RESULTS In this analysis, 43 patients were included. The average estimated glomerular filtration rate slope demonstrated a significant improvement after dapagliflozin treatment compared to that before the treatment (0.04 vs -0.55 ml/min/1.73 m2/year, P = .001). A good response rate was 69.8% and was associated with low average levels of C-reactive protein, a high frequency of angiotensin II receptor blocker (ARB) use, and a low frequency of tacrolimus use compared to nonresponse (0.08 ± 0.18 vs 0.25 ± 0.29 mg/dl, P = .03; 80.0 vs 38.4%, P = .01; 10.0 vs 76.9%, P < .01). CONCLUSIONS Dapagliflozin is effective for rheumatic musculoskeletal disease patients with CKD for preventing deterioration of renal function. Antihypertensive treatment with ARB and inflammation control without tacrolimus was associated with a high likelihood of favourable response to dapagliflozin.
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Affiliation(s)
- Hironari Hanaoka
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Jun Kikuchi
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Kazuoto Hiramoto
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Mitsuhiro Akiyama
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Shutaro Saito
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Yasushi Kondo
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Tatsuhiko Azegami
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Yuko Kaneko
- Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
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Salbas CS, Uslu S, Salbas E. Evaluation of lacrimal gland vascularization using superb microvascular imaging: A potential diagnostic tool in Sjögren's syndrome. Mod Rheumatol 2025; 35:320-325. [PMID: 39177379 DOI: 10.1093/mr/roae081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 08/08/2024] [Accepted: 08/16/2024] [Indexed: 08/24/2024]
Abstract
OBJECTIVES The aim of this study is to evaluate the superb microvascular imaging (SMI) findings of the lacrimal glands for the sonographic diagnosis of primary Sjögren's syndrome (pSS). METHODS Twenty-one patients with pSS and 20 healthy groups were evaluated. Dry eye symptoms and their effects on vision-related functions were evaluated with McMonnies and Ocular Surface Disease Index (OSDI) questionnaires. Lacrimal glands were evaluated by power Doppler ultrasonography (PDUS), colour Doppler ultrasonography (CDUS), and SMI. RESULTS Dry eye symptoms, as determined by McMonnies and OSDI, were significantly more severe in patients with pSS than in the control group (P = .001 and P = .021, respectively). Lacrimal gland vascular activity rates and hypoechoic areas were significantly higher in pSS patients compared to the control group (P < .05). The detection rates of the degree of vascularity in the lacrimal glands of patients with pSS were higher with SMI compared to CDUS and PDUS. In addition, SMI positively correlated with CDUS, PDUS, OSDI, and McMonnies. CONCLUSIONS Evaluation of the lacrimal gland by the SMI was found to be excellent in predicting the likelihood of individuals having pSS compared to CDUS and PDUS. This technique may serve as a reliable and noninvasive adjunctive tool for assessing the degree of lacrimal vascularity in pSS.
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Affiliation(s)
| | - Sadettin Uslu
- Department of Internal Medicine, Division of Rheumatology, Celal Bayar University School of Medicine, Manisa, Turkey
| | - Ender Salbas
- Department of Physical Medicine and Rehabilitation, Balikesir University Faculty of Medicine, Balikesir, Turkey
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Wang R, Chen X, Xu S, Jiang X, Liu J, Liu X, Ryu JH, Hu X. Prevalence and recurrence rates of spontaneous pneumothorax in patients with diffuse cystic lung diseases in China. Orphanet J Rare Dis 2025; 20:69. [PMID: 39934870 PMCID: PMC11816762 DOI: 10.1186/s13023-025-03587-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 01/29/2025] [Indexed: 02/13/2025] Open
Abstract
OBJECTIVES To investigate the prevalence and recurrence rates of spontaneous pneumothorax (SP) in patients with diffuse cystic lung diseases (DCLDs). METHODS We retrospectively identified and analyzed medical records of patients with DCLDs encountered at the First Affiliated Hospital of University of Science and Technology of China from Jan 1, 2017 to December 31, 2023. RESULTS A total of 289 patients were identified with DCLDs; 212 females and 77 males, with a median age of 48 years (range, 18-81 years). Among them, 89 (31%) patients had experienced SP; 59% among 115 patients with Birt-Hogg-Dubé (BHD), 34% of 41 patients with lymphangioleiomyomatosis (LAM, all women), 36% of 11 patients with pulmonary Langerhans cell histiocytosis (PLCH), none of 57 patients with Sjögren's syndrome-associated diffuse cystic lung disease (SS-DCLD), and 5% of 65 patients with no identifiable underlying disease (χ² = 90.585, P < 0.001). The overall recurrence rate of SP was higher with observation or chest tube placement strategy compared to surgical intervention, 59% vs. 11% (P < 0.001, 95% CI [0.1, -0.4]), respectively. The recurrence rate after surgical management was significantly lower compared to conservative management in patients with BHD (10% vs. 69%, P < 0.001, 95% CI [0.1, 0.3]) and LAM (20% vs. 57%, P = 0.322, 95% CI [0.1, 2.1]). Among patients with BHD, LAM, and PLCH, those who had pneumothorax as the initial presentation were diagnosed of their underlying disease at a significantly younger age (42.2 ± 13.0 years) compared to those without pneumothorax (48.1 ± 11.8 years) (P = 0.032, 95% CI [-8.24, -0.36]). Notably, eight of LAM patients who were treated with sirolimus after the initial SP did not experience recurrence of SP. CONCLUSION The risk of SP secondary to DCLDs was highest in patients with BHD, followed by those with PLCH and LAM. It was extremely low in SS-DCLD. Pneumothorax as the initial presentation often facilitated diagnosis of the underlying disease. Surgical treatment was associated with a lower recurrence rate of SP compared to nonsurgical management. In addition, sirolimus therapy may reduce the risk of pneumothorax recurrence in patients with LAM.
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Affiliation(s)
- Rui Wang
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
- WanNan Medical College, Wuhu, China
| | - Xianmeng Chen
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
- Center for Diagnosis and Management of Rare Diseases, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
| | - Shicheng Xu
- Department of Radiology, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
| | - Xianliang Jiang
- Department of Thoracic Surgery, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
| | - Jinli Liu
- Department of Dermatology, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
| | - Xuehan Liu
- Office of Scientific Research, Division of Life Sciences and Medicine, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
| | - Jay H Ryu
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | - Xiaowen Hu
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.
- Center for Diagnosis and Management of Rare Diseases, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China.
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Jeon H, Park Y, Lee JJ, Suh YS, Kwok SK, Park SH, Kim WU, Koh JH. The prevalence, clinical features, and long-term outcome of patients with primary Sjögren's syndrome with renal involvement. Sci Rep 2025; 15:4211. [PMID: 39905236 PMCID: PMC11794661 DOI: 10.1038/s41598-025-88368-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 01/28/2025] [Indexed: 02/06/2025] Open
Abstract
This multicenter, retrospective longitudinal study identified primary Sjögren's syndrome (pSS) patients with clinically significant renal involvement, and analyzed factors associated with predisposition. To investigate clinical features and long-term prognosis of renal involvement, we compared the clinical outcomes for the entire cohort based on the presence or absence of renal involvement. Among 1306 pSS patients (mean age, 51 ± 12 years; 98% female), 36 (2.8%) had renal involvement; 17 patients had tubular involvement, 15 had glomerular involvement, one had both, and 3 were unclassified. The presence of anti-La antibodies was associated with renal involvement. Over the median 5-year follow-up period, the renal function did not change significantly; however, 44% of patients with renal involvement showed impaired renal function at the last visit. Impaired renal function at the last visit was inversely associated with baseline renal function and hemoglobin levels. Among the entire cohort, the prevalence of lymphoproliferative disease (LPD) was significantly higher in pSS patients with renal involvement than those without. Renal involvement is a rare manifestation of pSS; however, it is associated with impaired renal function and LPD. Therefore, screening for renal involvement is important for preserving renal function and early detection of LPD.
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Affiliation(s)
- Howook Jeon
- Division of Rheumatology, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Youngjae Park
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jennifer Jooha Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yoo-Seok Suh
- Division of Rheumatology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung-Ki Kwok
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung-Hwan Park
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Wan-Uk Kim
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jung Hee Koh
- Division of Rheumatology, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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Cioni P, Chretien P, Goulvestre C, Ballot E, Khelifi-Touhami D, Mariette X, Nocturne G. Isolated anti-SS-B (La) antibodies: rare occurrence and lack of diagnostic value. RMD Open 2025; 11:e005212. [PMID: 39904568 PMCID: PMC11795515 DOI: 10.1136/rmdopen-2024-005212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 01/15/2025] [Indexed: 02/06/2025] Open
Abstract
OBJECTIVE Anti-SS-B antibodies are often associated with anti-SS-A in Sjögren's disease. Compared to anti-SS-A antibody positivity, the significance of the immunological profile anti-SS-B positive/anti-SS-A negative remains controversial. We aimed to evaluate the prevalence and diagnostic significance of isolated anti-SS-B antibodies. METHODS We conducted a retrospective study across three hospitals of the Assistance Publique-Hôpitaux de Paris. Patients with anti-SS-B positivity were identified using ELISA, addressable laser beam immunoassay (ALBIA) and immunodot assays. They were retained if anti-SS-B was positive in two techniques and anti-SS-A was absent. Clinical, biological and immunological data were extracted and presented in a descriptive analysis. RESULTS A total of 80 540 requests for anti-SS-B antibody testing were carried out over a period of 7.9 years. Anti-SS-B positivity was found in 1693 patients. Among them, 335 (19.8%) patients had isolated anti-SS-B in ELISA/ALBIA. Immunodot was performed in 186 of them and confirmed anti-SS-B positivity in 61 patients (3.6% of anti-SS-B positivity). 24 patients (39.3%) presented with a history of various autoimmune or autoinflammatory diseases and only 6 were diagnosed with a new connective tissue disease. After a median follow-up of 26 months, only two new diagnoses were made. CONCLUSION Anti-SS-B without anti-SS-A is exceedingly rare when accurately identified by a rigorous immunological approach. The initial anti-SS-B positivity does not correlate with a specific condition, both at the time of initial identification and after a 26-month follow-up period. This supports the fact that isolated anti-SS-B has no diagnostic or prognostic value.
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Affiliation(s)
- Paul Cioni
- Rhumatologie, CHU Bicêtre, Le Kremlin-Bicetre, Île-de-France, France
| | - Pascale Chretien
- Laboratoire d'Immunologie, CHU Bicêtre, Le Kremlin-Bicetre, Île-de-France, France
| | - Claire Goulvestre
- Laboratoire d'Immunologie, Hôpital Cochin, Paris, Île-de-France, France
| | - Eric Ballot
- Laboratoire d'Immunologie, Hôpital Saint-Antoine, Paris, Île-de-France, France
| | | | - Xavier Mariette
- Rhumatologie, CHU Bicêtre, Le Kremlin-Bicetre, Île-de-France, France
| | - Gaëtane Nocturne
- Rhumatologie, CHU Bicêtre, Le Kremlin-Bicetre, Île-de-France, France
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30
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Zhou M, Liu Y, Zhang S, Xie X, Li W, Cui L, Zhao H, Tang S, Hu X, Wu S, Peng J, Huang H, Ren W, Zhang Y, Xu N, Sun P, Liu Y, Zhang Z, Yu G, Su Y. Diagnostic value of a novel salivary gland ultrasound scoring system in IgG4-related sialadenitis. Rheumatology (Oxford) 2025; 64:747-755. [PMID: 38429955 DOI: 10.1093/rheumatology/keae121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 01/19/2024] [Accepted: 02/07/2024] [Indexed: 03/03/2024] Open
Abstract
OBJECTIVES To develop a novel ultrasound scoring system for the major salivary glands in patients with immunoglobulin G4-related sialadenitis (IgG4-RS) and assess its diagnostic value in a multicentre cohort of Chinese patients. METHODS Twenty clinicians (rheumatologists, stomatologists and radiologists) participated. The study was conducted in four steps: (i) defining the ultrasonography (US) elements, (ii) developing a novel ultrasound scoring system for US of the salivary glands, (iii) evaluation of inter- and intra-reader reliabilities using the new ultrasound scoring system, and (iv) assessing the diagnostic value of this novel ultrasound scoring system in IgG4-RS patients in a Chinese multicentre cohort. RESULTS A novel ultrasound scoring system for the salivary glands was developed, with total scores ranging from 0 to 34. The inter- and intra-reader reliabilities of the ultrasound scoring system were excellent (0.972 and 0.940, respectively). A total of 470 people were recruited in this study; 187 patients were diagnosed with IgG4-RS, and the remaining 283 people were diagnosed with non-IgG4-RS. Patients with IgG4-RS group had significantly higher US scores than the non-IgG4-RS group (mean US score = 16 vs 4, P < 0.001). The calculated area under the curve for the total US score was 0.852 (95% CI: 0.814, 0.891). The total US scores ≥9 showed a sensitivity of 75.4% and a specificity of 91.9%. Association analysis showed a positive correlation between total US scores and serum IgG4 levels and hypocomplementaemia (r = 0.221 and r = 0.349, respectively; P = 0.002 and P < 0.001, respectively) and a negative correlation between total US scores and serum C3 and C4 levels (r = -0.210 and r = -0.303, respectively; P = 0.005 and P < 0.001, respectively). CONCLUSION A novel semiquantitative ultrasound scoring system for patients with IgG4-RS was developed, with good diagnostic performance. The inter- and intra-reader reliabilities were excellent. US scores were correlated with IgG4, C3 and C4 levels and hypocomplementaemia.
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Affiliation(s)
- Mingzhu Zhou
- Department of Rheumatology and Immunology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yanying Liu
- Department of Rheumatology and Immunology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
| | - Shanshan Zhang
- Department of Ultrasound, Peking University People's Hospital, Beijing, China
| | - Xiaoyan Xie
- Department of Oral Radiology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Wei Li
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China
| | - Li Cui
- Department of Rheumatology and Immunology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Hanxue Zhao
- Department of Diagnostic Ultrasound, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Sumei Tang
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
| | - Xiangdong Hu
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Shanshan Wu
- Department of Clinical Epidemiology and Evidence-based Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jiajing Peng
- Department of Rheumatology and Immunology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Huilian Huang
- Department of Diagnostic Ultrasound, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Wei Ren
- Department of Diagnostic Ultrasound, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Ying Zhang
- Department of Diagnostic Ultrasound, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Ning Xu
- Department of Diagnostic Ultrasound, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Pengfei Sun
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yiqun Liu
- Department of Ultrasound, Peking University People's Hospital, Beijing, China
| | - Zuyan Zhang
- Department of Oral Radiology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Guangyan Yu
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China
| | - Yin Su
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
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Tsuyuki T, Kitamura M, Takatani M, Tsuji K, Torigoe K, Tsuji S, Fujita N, Yamaguchi Y, Mukae H, Nishino T. Simultaneous Presentation of Minimal Change Disease and Tubulointerstitial Nephritis Associated with Primary Sjögren's Syndrome and Hashimoto's Thyroiditis: A Case Report. Intern Med 2025:4747-24. [PMID: 39894500 DOI: 10.2169/internalmedicine.4747-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2025] Open
Abstract
A 78-year-old woman experienced systemic edema and was diagnosed with nephrotic syndrome and Hashimoto's thyroiditis (HT). A renal biopsy revealed minimal change disease (MCD) and tubulointerstitial nephritis, which resulted in the diagnosis of primary Sjögren's syndrome (PSS). PSS and HT can be complicated with MCD; however, there are no published case reports of MCD presenting with both conditions simultaneously. We aimed to inform nephrologists and rheumatologists about this rare condition through a literature review of renal outcomes in patients with MCD associated with PSS and HT.
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Affiliation(s)
- Tomohisa Tsuyuki
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Japan
- Department of Nephrology, Nagasaki Genbaku Hospital, Japan
| | - Mineaki Kitamura
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Miho Takatani
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Kiyokazu Tsuji
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Kenta Torigoe
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Sosuke Tsuji
- Department of Rheumatology, Nagasaki Genbaku Hospital, Japan
| | - Naruhiro Fujita
- Department of Endocrinology, Nagasaki Genbaku Hospital, Japan
| | | | - Hiroshi Mukae
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Tomoya Nishino
- Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Japan
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Li Y, He W, Zhou Y, Chen H, You P, Mu D, Ma Y, Gao Y, Xu K, Dong H, Cheng X. Advances in laboratory diagnosis of Sjogren's disease in children. Clin Chim Acta 2025; 567:120095. [PMID: 39681228 DOI: 10.1016/j.cca.2024.120095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 12/13/2024] [Accepted: 12/13/2024] [Indexed: 12/18/2024]
Abstract
Sjogren's disease (SjD) in children is a rare chronic autoimmune disease not fully recognized due to clinical manifestations different from adults. As such, new objective indicators are needed to supplement existing markers and assist in diagnosis. This review summarizes pathogenesis of SjD in children, current diagnostic criteria and research progress in laboratory diagnosis including serologic testing, saliva and tear analysis, histopathological examination as well as emerging markers of interest.
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Affiliation(s)
- Yuemeng Li
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China
| | - Wenxiu He
- Department of Stomatology, Peking Union Medical College Hospital, Peking Union Medical College&Chinese Academy of Medical Science, Beijing 100730, China
| | - Yu Zhou
- Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China
| | - Haotian Chen
- Department of Stomatology, Peking Union Medical College Hospital, Peking Union Medical College&Chinese Academy of Medical Science, Beijing 100730, China
| | - Pengyue You
- Department of Stomatology, Peking Union Medical College Hospital, Peking Union Medical College&Chinese Academy of Medical Science, Beijing 100730, China
| | - Danni Mu
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China
| | - Yichen Ma
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China
| | - Yumeng Gao
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China
| | - Kaiduo Xu
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology & Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Haitao Dong
- Department of Stomatology, Peking Union Medical College Hospital, Peking Union Medical College&Chinese Academy of Medical Science, Beijing 100730, China.
| | - Xinqi Cheng
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China.
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Chuang TL, Koo M, Lee YM, Tung CH, Wang YF. Association Between Quantitative Sialoscintigraphy and Antibody Profiles in Patients With Sjögren or Sicca Syndrome. Clin Nucl Med 2025; 50:109-118. [PMID: 39625850 DOI: 10.1097/rlu.0000000000005602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
PURPOSE This study analyzed the association between anti-Ro/SSA and anti-La/SSB antibody levels with quantitative and visual sialoscintigraphy patterns in patients suspected of having Sjögren or sicca syndrome. PATIENTS AND METHODS Medical records of patients who underwent sialoscintigraphy between April 2020 and May 2022 were reviewed. Associations between antibody levels and sialoscintigraphy parameters were evaluated using linear regression. Receiver operating characteristic curve analysis was used to identify antibody cutoff values for predicting flat-type patterns and the risk of Sjögren or sicca syndrome. RESULTS Of the 170 patients (mean age, 56.6 years; 78.8% female), 95.3% had dry mouth and eyes, 30% experienced polyarthralgia, and 66.5% were prescribed hydroxychloroquine. The most common sialoscintigraphy finding was the median-type time-activity curve (TAC) pattern. Anti-Ro/SSA and anti-La/SSB levels were significantly correlated with maximum accumulation or maximum secretion in the salivary glands. Receiver operating characteristic analysis for anti-Ro/SSA predicting a flat-type TAC pattern showed an area under the curve (AUC) of 0.659 to 0.780, with specificity between 82.1% and 86.3% for antibody levels greater than 85.2 units. Anti-Ro/SSA levels greater than 49.75 units predicted a higher risk of Sjögren or sicca syndrome, with an AUC of 0.622 and 83.9% specificity. Anti-La/SSB levels had no significant predictive value, with an AUC of 0.554. CONCLUSIONS Anti-Ro/SSA levels greater than 85.2 units were strong predictors of flat-type TAC patterns, indicating near-total salivary gland dysfunction and supporting their diagnostic utility in Sjögren or sicca syndrome.
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Affiliation(s)
| | - Malcolm Koo
- Department of Nursing, Tzu Chi University, Hualien
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Horai Y, Kurushima S, Shimizu T, Nakamura H, Kawakami A. A Review of the Impact of Sjögren's Syndrome and/or the Presence of Anti-Ro/SS-A Antibodies on Therapeutic Strategies for Rheumatoid Arthritis. J Clin Med 2025; 14:568. [PMID: 39860574 PMCID: PMC11766391 DOI: 10.3390/jcm14020568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 01/13/2025] [Accepted: 01/15/2025] [Indexed: 01/27/2025] Open
Abstract
Rheumatoid arthritis (RA) is an immune-mediated disease characterized by polyarthritis that affects the small joints of the bilateral upper and lower extremities. RA shares several common clinical symptoms with Sjögren's syndrome (SS), another rheumatic disease caused by the lymphocytic infiltration of exocrine glands, with dry eye and dry mouth being the two most common symptoms. Anti-Ro/SS-A antibodies, a diagnostic biomarker of SS, are positive in patients with RA at a certain rate. The coexistence of SS and/or positivity for anti-Ro/SS-A antibodies in patients with RA influences disease activity and the effectiveness of several classes of disease-modifying antirheumatic drugs (DMARDs). Furthermore, RA, SS, and certain DMARDs, including methotrexate, are associated with the onset of lymphoproliferative disorders (LPD). In contrast, several biological DMARDs, such as tocilizumab and rituximab, are plausible options without the risk of LPD relapse. Considering the results of the studies introduced in this article, RA with SS and/or positivity for anti-Ro/SS-A antibodies could be considered a phenotype different from isolated RA from the perspective of refractoriness to DMARD therapy and LPD risk. Hence, rheumatologists should observe caution when choosing DMARDs. Further studies are needed to establish the appropriate treatment for patients with RA, SS, and/or the presence of anti-Ro/SS-A antibodies.
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Affiliation(s)
- Yoshiro Horai
- Department of Rheumatology, Sasebo City General Hospital, Sasebo 857-8511, Japan;
- Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan; (T.S.); (A.K.)
| | - Shota Kurushima
- Department of Rheumatology, Sasebo City General Hospital, Sasebo 857-8511, Japan;
- Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan; (T.S.); (A.K.)
| | - Toshimasa Shimizu
- Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan; (T.S.); (A.K.)
- Clinical Research Center, Nagasaki University Hospital, Nagasaki 852-8501, Japan
| | - Hideki Nakamura
- Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan;
| | - Atsushi Kawakami
- Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan; (T.S.); (A.K.)
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Wu JY, Zhang JY, Xia WQ, Kang YN, Liao RY, Chen YL, Li XM, Wen Y, Meng FX, Xu LL, Wen SH, Liu HF, Li YQ, Gu JR, Lv Q, Ren Y. Predicting autoimmune thyroiditis in primary Sjogren's syndrome patients using a random forest classifier: a retrospective study. Arthritis Res Ther 2025; 27:1. [PMID: 39748261 PMCID: PMC11694358 DOI: 10.1186/s13075-024-03469-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 12/28/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND Primary Sjogren's syndrome (pSS) and autoimmune thyroiditis (AIT) share overlapping genetic and immunological profiles. This retrospective study evaluates the efficacy of machine learning algorithms, with a focus on the Random Forest Classifier, to predict the presence of thyroid-specific autoantibodies (TPOAb and TgAb) in pSS patients. METHODS A total of 96 patients with pSS were included in the retrospective study. All participants underwent a complete clinical and laboratory evaluation. All participants underwent thyroid function tests, including TPOAb and TgAb, and were accordingly divided into positive and negative thyroid autoantibody groups. Four machine learning algorithms were then used to analyze the risk factors affecting patients with pSS with positive and negative for thyroid autoantibodies. RESULTS The results indicated that the Random Forest Classifier algorithm (AUC = 0.755) outperformed the other three machine learning algorithms. The random forest classifier indicated Age, IgG, C4 and dry mouth were the main factors influencing the prediction of positive thyroid autoantibodies in pSS patients. It is feasible to predict AIT in pSS using machine learning algorithms. CONCLUSIONS Analyzing clinical and laboratory data from 96 pSS patients, the Random Forest model demonstrated superior performance (AUC = 0.755), identifying age, IgG levels, complement component 4 (C4), and absence of dry mouth as primary predictors. This approach offers a promising tool for early identification and management of AIT in pSS patients. TRIAL REGISTRATION This retrospective study was approved and monitored by the Ethics Committee of The Third Affiliated Hospital of Sun Yat-sen University (No.II2023-254-02).
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Affiliation(s)
- Jia-Yun Wu
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Jing-Yu Zhang
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Wen-Qi Xia
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Yue-Ning Kang
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Ru-Yi Liao
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Yu-Ling Chen
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Xiao-Min Li
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Ya Wen
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Fan-Xuan Meng
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Li-Ling Xu
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Sheng-Hui Wen
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Hui-Fen Liu
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Yuan-Qing Li
- School of Automation Science and Engineering, South China University of Technology, Guangzhou, China
- Research Center for Brain-Computer Interface, Pazhou Lab, Guangzhou, China
| | - Jie-Ruo Gu
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
| | - Qing Lv
- Department of Rheumatology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
| | - Yong Ren
- Scientific Research Project Department, Guangdong Artificial Intelligence and Digital Economy Laboratory (Guangzhou), Pazhou Lab, Guangzhou, China.
- The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
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Atik I, Atik S, Gul E. Effectiveness of shear wave elastography for assessing major salivary gland involvement in ankylosing spondylitis. Radiol Bras 2025; 58:e20240121. [PMID: 40094106 PMCID: PMC11908682 DOI: 10.1590/0100-3984.2024.0121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 01/10/2025] [Accepted: 01/18/2025] [Indexed: 03/19/2025] Open
Abstract
Objective To use shear wave elastography (SWE) in the evaluation of salivary glands in patients with ankylosing spondylitis (AS) who present with sicca symptoms. Materials and Methods This was a prospective controlled study of patients diagnosed with AS and exhibiting sicca symptoms (study group) and of healthy volunteers (control group). The levels of antinuclear, anti-Ro, and anti-La antibodies were determined in blood samples. In both groups, parotid and submandibular glands were evaluated by ultrasound and tissue stiffness was determined by SWE. Intraclass correlation coefficients were used in order to assess reliability. The differences between the two groups were assessed by statistical methods, and a ROC curve analysis was performed to determine the predictive values. Results A total of 66 patients with AS and 71 healthy volunteers were included in the study. There were no significant differences between the groups in terms of age or sex (p > 0.05). The intraand inter-rater reliability of SWE were good for the parotid gland (0.81-0.85 and 0.80, respectively) and for the submandibular gland (0.85-0.88 and 0.80, respectively). Statistically significant differences were found. Tissue stiffness in the parotid and submandibular glands, as determined by SWE, was significantly greater in the study group than in the control group (p < 0.05). Conclusion Although there was no histopathological correlation in the parotid and submandibular salivary glands of patients with AS and sicca symptoms compared with the healthy volunteers, quantitative measurements showed greater tissue stiffness in the former group. In patients with AS, SWE guides salivary gland biopsy, which is the gold standard for diagnosing Sjögren's syndrome.
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Affiliation(s)
- Irfan Atik
- Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkey
| | - Seda Atik
- Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkey
| | - Enes Gul
- Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkey
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Chen S, Fan Y, Wu Q, Zhang G, Wang Y, Li W, Yang S, Matucci-Cerinic M, Furst DE. Integrative Transcriptomic Analysis of Peripheral Blood Monocytes in Systemic Sclerosis and Shared Pathogenic Pathways in Autoimmune Diseases. Arch Med Res 2025; 56:103072. [PMID: 39208548 DOI: 10.1016/j.arcmed.2024.103072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 07/04/2024] [Accepted: 08/14/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Systemic sclerosis (SSc) is an autoimmune disease (AD), that receives less attention compared to rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and primary Sjögren's syndrome (pSS). This study aims to analyze transcriptional profiles and immune cell composition in peripheral blood mononuclear cells (PBMC) from SSc patients compared to other ADs. METHODS RNA-seq data from 119 untreated patients (eight with SSc, 42 with RA, 41 with pSS, 28 with SLE) and 20 healthy controls were analyzed. Bioinformatics tools were employed to identify differentially expressed genes (DEGs), biological functions and immune cell profiles unique to SSc and shared with other ADs. RESULTS 1,148 DEGs were found in SSc, with upregulated genes associated with megakaryocyte processes and downregulated genes associated with neutrophil function and immune response. DEGs, including ALDH1A1 and MEGF9, were associated with neutropenia. Upregulated transcription factors (TFs) were linked to embryonic hematopoiesis and downregulated TFs were involved in leukocyte differentiation and immune regulation. Comparative analysis with other ADs revealed common pathogenic pathways, emphasizing megakaryocyte proliferation. Neutrophils count was significantly decreased in ADs (p <0.001) compared to healthy controls. Comparative analysis highlighted common pathways, particularly in megakaryocyte proliferation, and unique genes (MEGF9, MMP8, and KRT family members) in SSc, suggesting roles in neutrophil function, skin integrity, and fibrosis. CONCLUSIONS This study identifies dysregulated gene expression (KRT and MMP8) associated with neutrophil function and increased megakaryocytes in SSc, highlighting common patterns across autoimmune diseases. These findings offer new insights into the potential pathogenesis of SSc, and help to explore new targets for the treatment.
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Affiliation(s)
- Shaoqi Chen
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Yu Fan
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong, China
| | - Qiulin Wu
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Guohong Zhang
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong, China
| | - Yukai Wang
- Department of Rheumatology and Immunology, Shantou Central Hospital, Shantou, Guangdong, China
| | - Weiping Li
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
| | - Shengli Yang
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Shanghai Academician Consulting and Academic Activities Center of Chinese Academy of Engineering, Shanghai, China.
| | - Marco Matucci-Cerinic
- Unit of Immunology, Rheumatology, Allergy and Rare diseases, San Raffaele Hospital, Milan, Italy
| | - Daniel E Furst
- Division of Rheumatology, School of Medicine, University of California at Los Angeles, California, USA
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Koh JH, Park Y, Lee J, Jeon H, Moon SJ, Kim YH, Min JK, Park SH, Kwok SK. Long-term outcome of interstitial lung disease in patients with primary Sjögren's syndrome: a retrospective observational study. Korean J Intern Med 2025; 40:148-159. [PMID: 39449593 PMCID: PMC11725482 DOI: 10.3904/kjim.2023.402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 11/27/2023] [Accepted: 06/10/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND/AIMS Interstitial lung disease (ILD) is a potentially serious but underdiagnosed manifestation of primary Sjögren's syndrome (pSS). This observational study investigated the prevalence and clinical course of ILD in pSS, together with prognostic factors. METHODS A multicenter, retrospective longitudinal study was performed using findings from baseline and follow-up pulmonary function tests and chest computed tomography. Predisposing factors for the development of ILD and acute exacerbation (AE) were identified using a logistic regression model. The risk factors for a significant decline of pulmonary function were determined by the Cox proportional hazard model. RESULTS A total of 1,306 patients with pSS were included in this study (female, 98%; mean age, 54 years). Among them, 79 patients with pSS were comorbid with ILD. ILD was more frequently found in male, older patients. Nonspecific interstitial pneumonia was the most prevalent imaging pattern in pSS-ILD (51%), followed by usual interstitial pneumonia (22%). At diagnosis with pSS-ILD, 54% of patients had restrictive pulmonary function, and 41% of patients initiated pharmacological treatment. During the median 4-year follow-up period, AE, a significant decline in pulmonary function, and death occurred in 19%, 29%, and 9% of patients with pSS-ILD, respectively. The neutrophil-to-lymphocyte ratio (NLR) increased 3 months prior to AE, and it was associated with AE. Older age at pSS-ILD diagnosis was a prognostic factor for a significant decline in pulmonary function. CONCLUSION ILD accounted for 6% of the comorbidity of pSS. AE was associated with a significant decline in pulmonary function, and the NLR may predict AE.
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Affiliation(s)
- Jung Hee Koh
- Division of Rheumatology, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Youngjae Park
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jennifer Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Howook Jeon
- Division of Rheumatology, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Su-Jin Moon
- Division of Rheumatology, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yong Hyun Kim
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jun-Ki Min
- Division of Rheumatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sung-Hwan Park
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seung-Ki Kwok
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Hou F, Cui Y, Ye L, Chen F, Wu C, Meng Y, Yuan P, Qiu X, Feng X, Jiang L. Metabolomic insights into idiopathic xerostomia: The central role of caffeine metabolism in salivary biochemistry. Arch Oral Biol 2025; 169:106102. [PMID: 39395317 DOI: 10.1016/j.archoralbio.2024.106102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 09/23/2024] [Accepted: 09/30/2024] [Indexed: 10/14/2024]
Abstract
OBJECTIVE This study aims to delineate the salivary metabolomic profile of patients with idiopathic xerostomia using untargeted metabolomics techniques, with the goal of addressing the lack of clear diagnostic markers and providing insights into the pathophysiological mechanisms of the condition. DESIGN In this observational, cross-sectional study, saliva samples from 33 patients with idiopathic xerostomia and 34 healthy controls were analyzed using Ultra Performance Liquid Chromatography Quadrupole Time of Flight Mass Spectrometry (UPLC-QTOF MS). Metabolomic profiling was complemented by multivariate statistical analysis to differentiate between affected individuals and controls. RESULTS Metabolomic analysis delineated a pronounced differentiation between patients with idiopathic xerostomia and healthy controls. A total of 195 metabolites displayed significant differential expression, each with a variable importance in projection (VIP) greater than 1 and a P-value less than 0.05. Pathway enrichment analysis, according to the Kyoto Encyclopedia of Genes and Genomes (KEGG), identified 22 metabolites that participated in 18 distinct metabolic pathways. Among these, the caffeine metabolism pathway, characterized by notable alterations in impact values (VIP, P-value, Log2-fold change, Rich factor), emerged as the most significantly disrupted, underscoring its potential role in the pathophysiology of idiopathic xerostomia (P = 0.0000395). CONCLUSIONS The salivary metabolomic profiling revealed distinct alterations in idiopathic xerostomia, with a significant reduction in caffeine metabolism pathways, underscoring potential neuropathic involvement. This study advances our understanding of the metabolic alterations in xerostomia, suggesting that salivary metabolomics may offer viable biomarkers for diagnosing and understanding the etiology of idiopathic xerostomia. Future research should focus on therapeutic targeting of these metabolic disturbances and evaluating their reversibility with treatment.
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Affiliation(s)
- Feifei Hou
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
| | - Yuan Cui
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China; State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shanxi Key Laboratory of Stomatology, Department of Oral Medicine, School of Stomatology, The Fourth Military Medical University, Xi'an, Shanxi, China.
| | - Lu Ye
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
| | - Fangman Chen
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
| | - Chuanji Wu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
| | - Yang Meng
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
| | - Peiyang Yuan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
| | - Xuemei Qiu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
| | - Xiaodong Feng
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
| | - Lu Jiang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
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Peng Y, Chen J, Ren Y, Yang D, Zhou Z, Shen X, Qian J, Jiang X, Zhao L, Fei Y, Chen H, Li M, Yang H, Zhang F. Mortality and Survival Analysis in Patients With Cancer Occurrence After Sjögren's Syndrome: A Long-Term Cohort Study in China. Int J Rheum Dis 2025; 28:e70059. [PMID: 39791505 DOI: 10.1111/1756-185x.70059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 12/06/2024] [Accepted: 12/26/2024] [Indexed: 01/12/2025]
Abstract
OBJECTIVE This study aimed to investigate the mortality, survival rates, and prognostic indicators of cancer occurrence after Sjögren's syndrome (SS-CA). METHODS The medical records of patients with SS-CA at the Peking Union Medical College Hospital (PUMCH) between January 2010 and August 2022 were retrieved. Clinical data and survival outcomes were compared to controls. The standard mortality ratio (SMR) versus the general population was calculated, and the survival and predictive markers of prognosis were analyzed using Kaplan-Meier curves and Cox regression. RESULTS In total, 114 SS-CA patients were included, with a median follow-up time of 105.1 (57.3-168.0) months. Non-Hodgkin lymphoma (32, 28.1%) was the most common cancer in patients with SS-CA. The SMR of SS-CA patients was 2.61 (95% confidence interval [CI] 1.73-3.77). Patients with SS-CA exhibited significantly inferior outcomes compared to controls (p = 0.010), with 5- and 10-year overall survival rates of 91.2% and 83.2%, respectively. SS patients with a diagnostic interval between SS and cancer (SS-CA diagnostic interval) ≤ 3 years or with hematological malignancies had poorer survival compared to those with a diagnostic interval > 3 years (p < 0.001) or with solid tumors (p = 0.019). Multivariate Cox regression analysis identified the prognosis-associated factors of SS-CA as age at SS diagnosis > 50 years (HR 3.129, 95% CI 1.224-7.998; p = 0.017), SS-CA diagnostic interval ≤ 3 years (HR 7.754, 95% CI 1.953-30.781; p = 0.004), and hematological malignancies (HR 2.648, 95% CI 1.201-5.838; p = 0.016). CONCLUSION Malignant comorbidities constituted a poor prognosis in patients with SS, wherein the SS-CA diagnostic interval and the types of cancer were associated with survival.
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Affiliation(s)
- Yezi Peng
- Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiana Chen
- Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yafei Ren
- Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Rheumatology and Immunology, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Dan Yang
- Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ziyue Zhou
- Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiangyi Shen
- Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- School of Medicine, Tsinghua University, Beijing, China
| | - Junyan Qian
- Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xu Jiang
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- National Infrastructure for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lidan Zhao
- Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yunyun Fei
- Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hua Chen
- Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mengtao Li
- Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huaxia Yang
- Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fengchun Zhang
- Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Pang R, Ma X, Guo H, Qi X. Meta-analysis of mortality-associated factors in primary Sjögren's syndrome patients with interstitial lung disease. Clin Rheumatol 2025; 44:23-31. [PMID: 39432139 PMCID: PMC11729075 DOI: 10.1007/s10067-024-07191-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/02/2024] [Accepted: 10/12/2024] [Indexed: 10/22/2024]
Abstract
The study aims to conduct a meta-analysis on 5-year survival rate and mortality-related factors in the patients with primary Sjögren's syndrome concomitant with interstitial lung disease (pSS-ILD). Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched various platforms and databases until November 22, 2023. We used the Newcastle-Ottawa Scale (NOS) for quality assessment and extracted study characteristics and effect sizes. The pooled 5-year survival rate, hazard ratios (HRs), and the corresponding 95% confidence intervals (95% CIs) were then calculated. A p-value of less than 0.05 was considered statistically significant. Patients with pSS-ILD. Mortality in patients with pSS-ILD. Out of 188 articles, seven met the inclusion criteria. The meta-analysis estimated a 5-year survival rate of 82% (73%-91%). Mortality-related factors estimated by the meta-analysis included older age (HRs = 1.06, 95% CI 1.03-1.09, P < 0.0001), history of smoking (HRs = 3.44, 95% CI 2.14-5.53, P < 0.00001), anti-SSA antibody positivity (HRs = 0.41, 95% CI 0.20-0.85, P = 0.02), anti-SSB antibody positivity (HRs = 0.42, 95% CI 0.18-0.98, P = 0.04), reduced forced vital capacity (FVC; HRs = 0.96, 95% CI 0.95-0.98, P < 0.0001), reduced 6-min walk distance (6MWD; HRs = 0.99, 95% CI 0.99-1.00, P = 0.0008), presence of a reticular abnormality (HRs = 3.03, 95% CI 1.54-5.95, P = 0.001), and decreased arterial partial pressure of oxygen (PaO2) levels (HRs = 0.99, 95% CI 0.97-1.00, P = 0.04). The 5-year survival rate for pSS-ILD is 82%. Older age, history of smoking, anti-SSA antibody negativity, anti-SSB antibody negativity, reduced FVC, reduced 6MWD, presence of a reticular abnormality, and decreased PaO2 levels increase the mortality risk in pSS-ILD.
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Affiliation(s)
- Ruochen Pang
- The Second Hospital of Hebei Medical University, No. 215, Heping West Road, Xinhua District, Shijiazhuang, 050000, Hebei Province, China
| | - Xiaopeng Ma
- The Second Hospital of Hebei Medical University, No. 215, Heping West Road, Xinhua District, Shijiazhuang, 050000, Hebei Province, China
| | - Huifang Guo
- Department of Rheumatology and Immunology, the Second Hospital of Hebei Medical University, No. 215, Heping West Road, Xinhua District, Shijiazhuang, 050000, Hebei Province, China
| | - Xuan Qi
- Department of Rheumatology and Immunology, the Second Hospital of Hebei Medical University, No. 215, Heping West Road, Xinhua District, Shijiazhuang, 050000, Hebei Province, China.
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Hosseini M, Jensen SS, Gotfredsen K, Hyldahl E, Pedersen AML. Prognosis of Single Implant-Supported Prosthesis in Patients With Primary Sjögren's Syndrome: A Five-Year Prospective Clinical Study. Clin Oral Implants Res 2025; 36:51-63. [PMID: 39235273 DOI: 10.1111/clr.14356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 07/29/2024] [Accepted: 08/14/2024] [Indexed: 09/06/2024]
Abstract
BACKGROUND Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease characterized by hyposalivation. Currently, there is limited evidence for the prognosis of dental implant treatment in Sjögren's syndrome. AIM/HYPOTHESIS We hypothesized comparable clinical outcomes of implant-supported restorations in pSS-patients and control subjects, and improvement in oral health-related quality of life 5 years after restoration. MATERIAL AND METHODS Patients with pSS and matched (age, gender, and tooth region) control group were recruited between June 2016 and March 2020. The clinical and radiological examination were performed, and patient-reported oral health impact profile (OHIP-49) questionnaire was used 2 months (baseline), 1, 3, and 5 years after prosthetic treatment. RESULTS We included 23 patients with pSS and 24 matched control subjects (all women, mean age: 57.1 years). The overall DMFT (decayed-missed-filled-tooth) was significantly higher (p = 0.008), symptoms of dry mouth were more severe (p = 0.001), and unstimulated and chewing-stimulated saliva flow rates were significantly lower (p < 0.001) in pSS than in control group. All implants survived with no implant mobility. At implant sites, the plaque index and probing depths did not differ (p = 0.301 and 0.446, respectively), but the gingival index was significantly higher (p = 0.003) in pSS than control group. The mean marginal bone loss, prosthetic complications, and clinician-reported aesthetic outcomes were similar in both groups after 5 years. The OHIP scores were significantly higher in the pSS than control group (p < 0.001) but reduced significantly in both groups (p = 0.026). CONCLUSION Replacement of missing single teeth with dental implants was successful in patients with pSS 5 years after restoration.
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Affiliation(s)
- Mandana Hosseini
- Research Section for Oral Health, Society and Technology/Oral Rehabilitation, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Simon Storgård Jensen
- Research Section for Oral Biology and Immunopathology/Oral Surgery, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Oral and Maxillofacial Surgery, Copenhagen University Hospital, Copenhagen, Denmark
| | - Klaus Gotfredsen
- Research Section for Oral Health, Society and Technology/Oral Rehabilitation, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Emil Hyldahl
- Research Section for Oral Biology and Immunopathology/Oral Surgery, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Anne Marie Lynge Pedersen
- Research Section for Oral Biology and Immunopathology/Oral Pathology and Medicine, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Nguyen Y, Beydon M, Gottenberg JE, Morel J, Perdriger A, Dernis E, Cornec D, Devauchelle-Pensec V, Sène D, Dieudé P, Couderc M, Fauchais AL, Larroche C, Vittecoq O, Salliot C, Hachulla E, Le Guern V, Mariette X, Seror R, Nocturne G. Distinct Pathophysiologic Pathways Support Stratification of Sjögren's Disease Based on Symptoms, Clinical, and Routine Biological Data. Arthritis Rheumatol 2024. [PMID: 39721742 DOI: 10.1002/art.43096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 10/14/2024] [Accepted: 11/06/2024] [Indexed: 12/28/2024]
Abstract
OBJECTIVE Recently, three distinct phenotypes of patients with Sjögren disease (SjD) have been described based on cluster analysis: B cell active with low symptoms (BALS), high systemic activity (HSA), and low systemic activity with high symptoms (LSAHS). We aimed to assess whether these clusters were associated with distinct biomarkers and the prognostic value of interferon (IFN) signature. METHODS The Assessment of Systemic Signs and Evolution in Sjögren's Syndrome cohort is a 20-year prospective cohort of patients with SjD. The following biomarkers were compared: IFN-α2, IFN-γ, CXCL10, CXCL13, BAFF, interleukin (IL)-7, fms-like tyrosine kinase 3 ligand, CCL19, and tumor necrosis factor receptor 2 (TNF-RII). IFN signature was assessed using transcriptomic analysis. We then compared systemic and symptomatic evolution, and the risk of new immunosuppressant prescription and of lymphoma, according to the IFN signature across the three clusters. RESULTS A total of 395 patients (94% female, median age 53 [interquartile range 43-63] years) were included. Higher levels of CXCL13, IL-7, and TNF-RII were found in the BALS and HSA clusters compared with the LSAHS cluster. A high IFN signature was mainly found in the BALS cluster (57%, vs 48% and 38% in the HSA and LSAHS clusters, respectively). This IFN signature was mainly driven by type I IFN, with higher levels of IFN-α2. In the BALS cluster, a high IFN signature was associated with a higher risk of new immunosuppressant treatment (hazard ratio 9.38; 95% confidence interval 1.22-72.16). All lymphoma occurred in patients with high IFN signature. CONCLUSION The three SjD clusters displayed distinct expressions of IFN signature and markers of T and B cell activation, confirming distinct pathophysiologic mechanisms. High IFN signature could predict systemic evolution in the BALS cluster.
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Affiliation(s)
- Yann Nguyen
- Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Université Paris-Saclay, Le Kremlin-Bicêtre, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, Université Paris Cité, Clichy, Centre de Recherche en Epidémiologie et Statistiques, INSERM UMR 1153, Université Paris Cité, Paris, France
| | - Maxime Beydon
- Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Université Paris-Saclay, Le Kremlin-Bicêtre, Hôpital Beaujon, Assistance Publique - Hôpitaux de Paris, Université Paris Cité, Clichy, Paris, France
| | | | - Jacques Morel
- Centre Hospitalier Universitaire de Montpellier and PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France
| | - Aleth Perdriger
- Centre Hospitalier Universitaire de Rennes, Université de Rennes, Rennes, France
| | | | - Divi Cornec
- Centre Hospitalier Universitaire de Brest, INSERM 1227, LBAI, Université de Bretagne Occidentale, Centre de Référence des Maladies Auto-Immunes Rares de l'Adulte, Brest, France
| | - Valérie Devauchelle-Pensec
- Centre Hospitalier Universitaire de Brest, INSERM 1227, LBAI, Université de Bretagne Occidentale, Centre de Référence des Maladies Auto-Immunes Rares de l'Adulte, Brest, France
| | - Damien Sène
- Hôpital Lariboisière, Assistance Publique - Hôpitaux de Paris, Paris, France
| | - Philippe Dieudé
- Hôpital Bichat-Claude Bernard, AP-HP, INSERM UMR 1152, Paris Cité University, Paris, France
| | - Marion Couderc
- Centre Hospitalier Universitaire de Clermont-Ferrand and INSERM UMR 1240, Clermont Auvergne University, Clermont-Ferrand, France
| | | | - Claire Larroche
- Assistance Publique - Hôpitaux de Paris, Hôpital Avicenne, Bobigny, France
| | | | | | - Eric Hachulla
- Referral Centre for Rare Systemic Auto-immune and Auto-inflammatory Diseases North North-West Mediterranean and Guadeloupe (CeRAINOM), INSERM, Centre Hospitalier Universitaire de Lille, U1286 - INFINITE, University of Lille, Lille, France
| | - Véronique Le Guern
- National Referral Centre for Rare Autoimmune and Systemic Diseases, Hôpital Cochin, AP-HP Centre, Université Paris Cité, Paris, France
| | - Xavier Mariette
- Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Université Paris-Saclay, Center for Immunology of Viral Infections and Auto-immune Diseases (IMVA), Institut pour la Santé et la Recherche Médicale (INSERM) UMR 1184, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France
| | - Raphaèle Seror
- Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Université Paris-Saclay, Center for Immunology of Viral Infections and Auto-immune Diseases (IMVA), Institut pour la Santé et la Recherche Médicale (INSERM) UMR 1184, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France
| | - Gaëtane Nocturne
- Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Université Paris-Saclay, Center for Immunology of Viral Infections and Auto-immune Diseases (IMVA), Institut pour la Santé et la Recherche Médicale (INSERM) UMR 1184, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France
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Zhang X, Liao Z, Chen Y, Lu H, Wang A, Shi Y, Zhang Q, Wang Y, Li Y, Lan J, Chen C, Deng C, Zhuang W, Liu L, Qian H, Chen S, Li Z, Shi G, Liu Y. A non-invasive model for diagnosis of primary Sjogren's disease based on salivary biomarkers, serum autoantibodies, and Schirmer's test. Arthritis Res Ther 2024; 26:217. [PMID: 39695856 DOI: 10.1186/s13075-024-03459-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 12/08/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Minor salivary gland (MSG) biopsy is a critical but invasive method for the classification of primary Sjögren's disease (pSjD). Here we aimed to identify salivary proteins as potential biomarkers and to establish a non-invasive prediction model for pSjD. METHODS Liquid chromatography-tandem mass spectrometry was conducted on whole saliva samples from patients with pSjD and non-Sjögren control subjects (non-pSjD). Proteins involved in immune processes were upregulated in the pSjD group, such as complement C3 (C3), complement factor B (CFB), clusterin (CLU), calreticulin (CALR), and neutrophil elastase (NE), which were further confirmed by ELISA. Multivariate logistic regression analyses were performed to identify markers that differentiated pSjD from non-pSjD; receiver operating characteristic (ROC) curves were constructed. A diagnostic model based on the combination of salivary biomarkers (CFB, CLU, and NE), serum autoantibodies (anti-SSA /Ro60 and anti-SSA/Ro52), and Schirmer's test was evaluated in 186 patients (derivation cohort) with replication in 72 patients (validation cohort). RESULTS In multivariate analyses, CFB, CLU, and NE were independent predictors of pSS. A model based on the combination of salivary biomarkers (CFB, CLU, and NE), serum autoantibodies (anti-SSA and anti-Ro52), and Schirmer's test achieved significant discrimination of pSS. In the derivation cohort, the area under curve (AUC) of the ROC was 0.930 (95% CI 0.877-0.965, P < 0.001), with a sensitivity and specificity of 84.85% and 92.45%, respectively. Notably, similar results were obtained in a validation cohort. CONCLUSION The 6-biomarker panel could provide a novel non-invasive tool for the classification of pSjD.
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Affiliation(s)
- Xinwei Zhang
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Zhangdi Liao
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Department of Rheumatology and Clinical Immunology, The First Hospital of Nanchang, Nanchang, 330008, China
| | - Yangchun Chen
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Huiqin Lu
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Aodi Wang
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Yingying Shi
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Qi Zhang
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Ying Wang
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Yan Li
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Jingying Lan
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Chubing Chen
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Chaoqiong Deng
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Wuwei Zhuang
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Lingyu Liu
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Hongyan Qian
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Shiju Chen
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China
| | - Zhibin Li
- Epidemiology Research Unit, Center of Translational Medical Research, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, XM, 361000, China
| | - Guixiu Shi
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China.
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China.
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China.
| | - Yuan Liu
- Department of Rheumatology and Clinical Immunology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 55 Zhenhai Road, Xiamen, XM, 361000, China.
- Xiamen Municipal Clinical Research Center for Immune Diseases, Xiamen, XM, 361000, China.
- Xiamen Key Laboratory of Rheumatology and Clinical Immunology, Xiamen, XM, 361000, China.
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Madej M, Proc K, Wawryka P, Morgiel E, Sebastian M, Wiland P, Sebastian A. The analysis of the pulmonary domain involvement in Sjögren's disease. Ther Adv Musculoskelet Dis 2024; 16:1759720X241305218. [PMID: 39691174 PMCID: PMC11650598 DOI: 10.1177/1759720x241305218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 11/20/2024] [Indexed: 12/19/2024] Open
Abstract
Background The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) pulmonary domain is used to assess the activity of respiratory system involvement in Sjögren's disease (SjD). The most unfavorable form of respiratory involvement in SjD, after lymphomas, is interstitial lung disease (ILD). Objectives The aim of the study was to assess the involvement of the respiratory system in SjD patients and the occurrence of ILD in high-resolution computed tomography (HRCT), depending on immunological markers, the influence of cigarette smoking, and the age of the patients. Design Single-center, registry, cohort study. Methods Among all SjD patients, a group with involvement in the pulmonary domain was distinguished. This group was later subjected to a detailed analysis of immunological and serological markers and chest imaging tests. Results In all, 64 patients out of 299 with SjD had involvement in the pulmonary domain defined according to the ESSDAI definition. The most frequently reported clinical symptoms of respiratory system involvement included dryness and chronic cough (over 80% of patients), followed by shortness of breath. Nine percent of patients with changes in lungs were asymptomatic. Patients with pulmonary involvement were older (54 vs 48 years, p < 0.05). In the subpopulation of patients with SjD and pulmonary involvement, the presence of rheumatoid factor (73% vs 60%, p < 0.05), and hematological domain involvement according to ESSDAI (54% vs 37%, p < 0.05) were more common. In the group of 64 patients with a positive pulmonary domain, 34 (53%) had ILD on HRCT. A higher incidence of comorbidities was found in the population of patients with ILD. No correlation was found between the type of lung involvement and the immunological profile, inflammatory markers, age, and smoking habit. Conclusion Involvement of the pulmonary domain is common in patients with SjD. However, the clinical picture is very heterogeneous, which determines the subsequent personalization of treatment.
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Affiliation(s)
- Marta Madej
- Department and Clinic of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Krzysztof Proc
- Department of Rheumatology and Internal Medicine, Wroclaw Medical University Hospital, Wroclaw, Poland
| | - Piotr Wawryka
- Department of Rheumatology and Internal Medicine, Wroclaw Medical University Hospital, Wroclaw, Poland
| | - Ewa Morgiel
- Department and Clinic of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Maciej Sebastian
- Department and Clinic of General, Minimally Invasive and Endocrine Surgery, Wroclaw Medical University, Wroclaw, Poland
| | - Piotr Wiland
- Department and Clinic of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - Agata Sebastian
- Department and Clinic of Rheumatology and Internal Medicine, Wroclaw Medical University, Borowska 213, Wroclaw 50-556, Poland
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Pozzan R, Salton F, Confalonieri P, Trotta L, Barbieri M, Reccardini N, Torregiani C, Screm G, Hughes M, Baratella E, Confalonieri M, Mondini L, Ruaro B. Autoantibodies in sarcoidosis: Innocent bystander or promising biomarker for organ involvement? SARCOIDOSIS, VASCULITIS, AND DIFFUSE LUNG DISEASES : OFFICIAL JOURNAL OF WASOG 2024; 41:e2024056. [PMID: 39655585 PMCID: PMC11708945 DOI: 10.36141/svdld.v41i4.16043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 08/12/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND AND AIM Sarcoidosis is a rare inflammatory disease that can affect any organ in the body, but most commonly involves lungs and lymph nodes. Sarcoidosis is often considered an autoimmune disease, attributed to many factors, including autoantigen-specific T cells, antibodies producing B lymphocytes, autoimmune inflammation, although its exact cause and classification are still under debate.The aim of our study was to evaluate the possible role of autoantibodies, such as anti-nuclear (ANA), extractable nuclear antigen (ENA) and antiphospholipids, in sarcoidosis patients. METHODS We conduct a retrospective study on our patients with confirmed diagnosis of sarcoidosis involving lungs, lymph nodes and multiple organs, and we collected and analyzed data on blood and urine tests (C-reactive protein, CRP, amount of calcium in blood and urine, CD4/CD8 ratio, lymphocyte count), lung function, radiological patterns, ongoing treatments (steroid therapy, hydroxychloroquine or methotrexate, other immunosuppressive agents). RESULTS We enrolled 328 sarcoidosis patients, and we focused our attention on 32 patients with positive ANA antibodies (11%), observing a high percentage of them with sarcoidosis involving the lungs (77%), but more specifically a significant discrepancy, in percentage terms, in the blood CD4/CD8 ratio. In the ANA-positive group we observed 26% of patients with a high blood CD4/CD8 ratio (average CD4/CD8 ratio of 2.41), whereas in the ANA-negative group, patients with a high CD4/CD8 ratio (average ratio 1.78) represented a much smaller percentage (13%). This finding may be a source of further investigation for other studies on the topic. CONCLUSIONS Analysis of autoantibodies expressed in our case series did not identify a specific autoantibodies pattern in sarcoidosis. Few studies have analyzed autoantibody patterns in sarcoidosis patients and involved smaller populations. In conclusion, our study evaluates a sizable population, and underlines the need for further, larger clinical studies to evaluate possible associations between sarcoidosis and autoimmunity.
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Affiliation(s)
- Riccardo Pozzan
- Pulmonology Unit, University of Trieste, Department of Medical Surgical and Health Sciences, Hospital of Cattinara, Trieste, Italy
- These authors contributed equally to this work
| | - Francesco Salton
- Pulmonology Unit, University of Trieste, Department of Medical Surgical and Health Sciences, Hospital of Cattinara, Trieste, Italy
- These authors contributed equally to this work
| | - Paola Confalonieri
- Pulmonology Unit, University of Trieste, Department of Medical Surgical and Health Sciences, Hospital of Cattinara, Trieste, Italy
| | - Liliana Trotta
- Pulmonology Unit, University of Trieste, Department of Medical Surgical and Health Sciences, Hospital of Cattinara, Trieste, Italy
| | - Mariangela Barbieri
- Pulmonology Unit, University of Trieste, Department of Medical Surgical and Health Sciences, Hospital of Cattinara, Trieste, Italy
| | - Nicolò Reccardini
- Pulmonology Unit, University of Trieste, Department of Medical Surgical and Health Sciences, Hospital of Cattinara, Trieste, Italy
| | - Chiara Torregiani
- Pulmonology Unit, University of Trieste, Department of Medical Surgical and Health Sciences, Hospital of Cattinara, Trieste, Italy
| | - Gianluca Screm
- Pulmonology Unit, University of Trieste, Department of Medical Surgical and Health Sciences, Hospital of Cattinara, Trieste, Italy
| | - Michael Hughes
- Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester & Salford Royal NHS Foundation Trust, Manchester, UK
| | - Elisa Baratella
- Department of Radiology, Department of Medicine, Surgery and Health Science, University of Trieste, Trieste, Italy
| | - Marco Confalonieri
- Pulmonology Unit, University of Trieste, Department of Medical Surgical and Health Sciences, Hospital of Cattinara, Trieste, Italy
| | - Lucrezia Mondini
- Pulmonology Unit, University of Trieste, Department of Medical Surgical and Health Sciences, Hospital of Cattinara, Trieste, Italy
- These authors contributed equally to this work
| | - Barbara Ruaro
- Pulmonology Unit, University of Trieste, Department of Medical Surgical and Health Sciences, Hospital of Cattinara, Trieste, Italy
- These authors contributed equally to this work
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Chang ML, Le PH, Chen WT, Chen TD, Su CW, Chen CJ, Lin CY, Wu CH, Kuo CJ, Sung KF, Chien RN. Distinct characteristics of various autoimmune liver diseases: A 22-year hospital-based study in Taiwan. J Gastroenterol Hepatol 2024; 39:2835-2844. [PMID: 39307997 DOI: 10.1111/jgh.16736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 08/13/2024] [Accepted: 08/27/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND AND AIM The characteristics of autoimmune liver diseases (AILDs), including primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and PBC-AIH overlap syndrome (OS), have rarely been investigated and compared in Asia. METHODS At the Taiwan tertiary referral center, 330 PBC patients (87% treated with ursodeoxycholic acid [UDCA]), 143 AIH patients (94.4% treated with immunosuppressive therapy [IST]) and 21 PBC-AIH OS patients (85.7% treated with UDCA and IST) were enrolled. RESULTS Compared with AIH patients, PBC patients were older at baseline and had greater female-to-male sex ratios, alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT) levels, and liver cirrhosis (LC), dyslipidemia, and hepatic and cardiometabolic complication rates. PBC patients had the lowest transaminase levels, whereas AIH patients had the highest transaminase levels. PBC patients had greater 22-year all-cause mortality and liver transplantation (ACMaLT) (43.5 vs 25.4%, P = 0.004), LC (75 vs 58.5%, P < 0.01), dyslipidemia (54.4 vs 45.9%, P = 0.001), and cerebrovascular accident (11.3 vs 0.8%, P = 0.019) cumulative incidences (CIs) than did AIH patients; PBC-AIH OS patients had greater systemic lupus erythematosus (28.9 vs 8.9%, P = 0.009) CI than did PBC patients. Baseline ALP (hazard ratio: 1.001), albumin (0.514), platelet count (0.997), and LC (3.438) were associated with ACMaLT; age (1.110), albumin (0.350), cirrhosis (46.219), and hepatitis C virus antibody positivity (5.068) were associated with hepatocellular carcinoma (HCC); and female sex (2.183) and body mass index (1.054) were associated with autoimmune diseases. CONCLUSIONS Compared with AIH patients, PBC patients had greater cardiometabolic CI, and ACMaLT CI, which was associated with cholestasis, liver functional reserve and LC. Older AILD patients with LC and females with obesity demand special caution for the development of HCC and extrahepatic autoimmune diseases, respectively.
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Affiliation(s)
- Ming-Ling Chang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, New Taipei City, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Puo-Hsien Le
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, New Taipei City, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wei-Ting Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, New Taipei City, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Tai-Di Chen
- Department of Anatomic Pathology, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan
- School of Medicine, National Tsing Hua University, Hsinchu, Taiwan
| | - Chung-Wei Su
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, New Taipei City, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Jen Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, New Taipei City, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Yu Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, New Taipei City, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chi-Huan Wu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, New Taipei City, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chia-Jung Kuo
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, New Taipei City, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Kei-Feng Sung
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, New Taipei City, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Rong-Nan Chien
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, New Taipei City, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Yang Y, Li M, Ding L, Zhang Y, Liu K, Liu M, Li Y, Luo H, Zuo X, Zhang H, Guo M. EZH2 promotes B-cell autoimmunity in primary Sjogren's syndrome via METTL3-mediated m6A modification. J Autoimmun 2024; 149:103341. [PMID: 39577129 DOI: 10.1016/j.jaut.2024.103341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 11/05/2024] [Accepted: 11/14/2024] [Indexed: 11/24/2024]
Abstract
OBJECTIVE Enhancer of zeste homologue 2 (EZH2) plays an important role in promoting B-cell activation and differentiation. This study aimed to elucidate the role of EZH2 in the B-cell autoimmune response in primary Sjögren's syndrome (pSS) and to explore the therapeutic potential of inhibiting EZH2 in pSS. METHODS Single-cell RNA sequencing analysis of B cells in peripheral blood from pSS patients was conducted to identify abnormal expression of EZH2 and METTL3 in B-cell subsets. The levels of EZH2 were further validated across multiple B-cell subsets and the salivary glands (SGs) of pSS patients, as well as three different mouse models of Sjögren's syndrome (SS). Correlation analyses were performed to explore the relationship between the expression of EZH2 and clinical features of pSS patients. Following EZH2 inhibition, SS-like signs and antibody production were assessed in an experimental Sjögren syndrome (ESS) mouse model. RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) data post-EZH2 inhibition were bioinformatically analyzed to identify the EZH2 targets in pSS. ChIP-qPCR was performed to validate the binding of H3K27me3 to the CDKN1A promoter. Flow cytometric apoptosis analysis and Carboxy Fluorescein Succinimidyl Ester (CFSE) assay were used to assess the impact of an EZH2 inhibitor on B-cell apoptosis and proliferation. Additionally, METTL3 expression and its correlation with disease activity were analyzed in pSS patients. EZH2 expression was examined after METTL3 knockdown. METTL3-RNA immunoprecipitation (RIP) and actinomycin D assays were conducted to confirm the direct binding of METTL3 to EZH2 mRNA and its impact on mRNA stability. M6A-RIP-qPCR was performed to validate the presence of m6A modifications on EZH2 mRNA. RESULTS EZH2 was found upregulated in multiple B-cell subsets from the peripheral blood and SGs of pSS patients, as well as in three different animal models of SS. The expression of EZH2 in B cells was positively correlated with the ESSDAI score, which is a measure of disease activity. With treatment of EZH2 inhibitor, SS-like signs alleviated and autoantibody production reduced in ESS mice. Similarly, in pSS patients, METTL3 expression was increased in the SGs and peripheral blood CD19+ B cells, also showing a positively correlated with the ESSDAI score. With knockdown of METTL3, the expression of EZH2 reduced. Mechanistically, EZH2 inhibited B-cell apoptosis and promoted B-cell proliferation by catalyzing H3K27me3 modification at the CDKN1A locus. Furthermore, METTL3 bound to EZH2 mRNA and increased m6A modification on EZH2 mRNA, enhancing its stability and promoting EZH2 expression. CONCLUSIONS The upregulation of EZH2 mediated by METTL3 is implicated in the B-cell autoimmune response in pSS. Inhibition of EZH2 presents a promising therapeutic strategy for pSS treatment.
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Affiliation(s)
- Yiying Yang
- Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, Hunan, China; Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China; Postdoctoral Research Station of Biology, School of Basic Medicine Science, Central South University, Changsha, Hunan, China
| | - Muyuan Li
- Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, Hunan, China; Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China; Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Liqing Ding
- Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ying Zhang
- Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, Hunan, China; Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China
| | - Ke Liu
- Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, Hunan, China; Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China
| | - Meidong Liu
- Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, Hunan, China; Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China
| | - Yisha Li
- Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Hui Luo
- Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xiaoxia Zuo
- Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Huali Zhang
- Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, Hunan, China; Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, Hunan, China.
| | - Muyao Guo
- Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
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Cen Z, Cen T, Ding Q, Zhang Y, Tang P, Lv C, Wu T. Outcomes and predictors of progression in progressive pulmonary fibrosis. Ann Med 2024; 56:2406439. [PMID: 39310989 PMCID: PMC11421158 DOI: 10.1080/07853890.2024.2406439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 06/24/2024] [Accepted: 07/01/2024] [Indexed: 09/26/2024] Open
Abstract
BACKGROUND Progressive pulmonary fibrosis (PPF) is a general term for a class of interstitial lung diseases (ILDs) characterized by a progressive fibrosing (PF) phenotype. Patients with PPF have decreased lung function, exercise ability, and quality of life. The purpose of this study was to investigate the clinical characteristics, potential associated factors for disease progression, and survival outcomes of patients in the PPF population. METHODS This study retrospectively reviewed the data of patients diagnosed with ILD between January 2011 and December 2022 at The First Affiliated Hospital of Ningbo University. A PF phenotype was defined based on the criteria that were used in the PPF clinical practice guidelines, which led to the identification of 92 patients with a PF phenotype among the 177 patients with fibrotic ILD. Baseline clinical information and laboratory parameters were collected and analysed in our cohort. RESULTS Patients in the PPF group had higher tumour marker levels and lower pulmonary function test results at baseline than did those in the non-PPF group. According to the multivariate logistic regression analysis, age >65 years (OR 2.71, 95% CI 1.26-5.89; p = 0.011), LDH >245 U/L (OR 3.07, 95% CI 1.39-6.78; p = 0.006), CA-153 > 35 U/mL (OR 3.16, 95% CI 1.25-7.97; p = 0.015), FVC <60% predicted (OR 4.82, 95% CI 1.60-14.51; p = 0.005), DLCO <50% predicted (OR 3.21, 95% CI 1.43-7.21; p = 0.005), and the UIP-like pattern on chest HRCT (OR 3.65, 95% CI 1.33-10.07; p = 0.012) were potentially associated with the progression of fibrotic interstitial lung diseases (f-ILDs) to PPF. Furthermore, the PPF group had a poorer survival rate than the non-PPF group (p = 0.0045). According to the multivariate Cox regression analysis, an SPAP ≥ 37 mmHg (HR 2.33, 95% CI 1.09-5.00; p = 0.030) and acute exacerbation (HR 2.88, 95% CI 1.26-6.59; p = 0.012) were identified as significant prognostic factors for mortality in patients with PPFs. CONCLUSIONS Patients who were older, had high CA-153 and LDH levels, had poor pulmonary function test results, or had a UIP-like pattern on chest HRCT were more likely to have indications for the progression of f-ILD to PPF. Increased SPAP and AE are independent risk factors for the prognosis of PPF patients, so additional attention should be given to such patients.
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Affiliation(s)
- Zekai Cen
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Tiantian Cen
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Qunli Ding
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Yun Zhang
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Pan Tang
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Chengna Lv
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Tingting Wu
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Respiratory Disease of Ningbo, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
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50
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Iwaya C, Iwata J. Associations between metabolic disorders and Sjögren's disease. JAPANESE DENTAL SCIENCE REVIEW 2024; 60:232-238. [PMID: 39502167 PMCID: PMC11535258 DOI: 10.1016/j.jdsr.2024.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 06/24/2024] [Accepted: 06/27/2024] [Indexed: 11/08/2024] Open
Abstract
Sjögren's disease (SjD) is a systemic autoimmune disorder characterized by dry eyes and mouth caused by chronic inflammation and is often accompanied by various extra-glandular manifestations, including fatigue and diffuse pain. Although the pathogenesis of the disease remains elusive, several factors (e.g. environmental, genetic and hormonal factors, abnormal metabolic status) are associated with this condition. Accumulating evidence suggests a potential role of cholesterol metabolism in immune and non-immune modulation in various diseases. In this review, we summarize the current findings on the associations between cholesterol metabolism and SjD.
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Affiliation(s)
- Chihiro Iwaya
- Department of Diagnostic & Biomedical Sciences, The University of Texas Health Science Center at Houston (UTHealth), School of Dentistry, Houston, Texas 77054, USA
- Center for Craniofacial Research, The University of Texas Health Science Center at Houston, School of Dentistry, Houston, TX 77054, USA
| | - Junichi Iwata
- Department of Diagnostic & Biomedical Sciences, The University of Texas Health Science Center at Houston (UTHealth), School of Dentistry, Houston, Texas 77054, USA
- Center for Craniofacial Research, The University of Texas Health Science Center at Houston, School of Dentistry, Houston, TX 77054, USA
- MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA
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