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Ivanova I, Svilenska T, Maisch T, Karrer S, Niebel D, Berneburg M, Kurz B. The role of UV-induced cutaneous matrix metalloproteinases and mi-RNAs in the pathogenesis of lupus erythematosus. J Transl Autoimmun 2025; 10:100265. [PMID: 39835284 PMCID: PMC11743922 DOI: 10.1016/j.jtauto.2024.100265] [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: 11/25/2024] [Revised: 12/24/2024] [Accepted: 12/27/2024] [Indexed: 01/22/2025] Open
Abstract
Cutaneous (CLE) and systemic lupus erythematosus (SLE) are autoimmune diseases with a multifactorial pathogenesis. Ultraviolet radiation (UVR) is the most important trigger of CLE; however, the degree of photosensitivity varies between the clinical subtypes. The expression of matrix metalloproteinases (MMPs)-important enzymes involved in skin turnover and homeostasis-is modulated by UVR. To investigate the causality of the clinically observed effects of UVR, sun-exposed lesional skin samples from patients with different subtypes of lupus erythematosus (LE) were examined by immunohistochemistry for the expression of MMP1 and MMP28 and compared with biopsies from polymorphous light eruption (PLE) and healthy skin (HS). The expression of micro-RNAs (miR-31 and miR-150)-regulators of MMP expression and cellular metabolism-in the samples was determined by in-situ hybridization and correlated with the expression of the glucose transporter 1 (GLUT1) receptor to examine potential metabolic regulation. To assess potential UVR regulation of MMP28, we performed in vitro experiments in healthy keratinocytes and fibroblasts. MMP28 expression was differentially affected by UVA1 and UVB irradiation in keratinocytes and fibroblasts. Compared with all other LE subtypes, as well as PLE and HS samples, MMP28 expression in Chilblain LE skin showed a distinct vertical distribution, reaching as far as the upper layers of the dermis. This vertical expression pattern coincided with decreased GLUT1 levels and with increased expression of miR-31 and miR-150 in the epidermis of patients with Chilblain LE. These data provide evidence for a potential metabolic dysregulation that may play a role in the etiology of LE. Furthermore, our results suggest MMP28 as a novel complementary marker in Chilblain LE diagnosis.
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Affiliation(s)
- I. Ivanova
- Department of Dermatology, University Medical Center Regensburg, 93042, Regensburg, Germany
| | - T. Svilenska
- Department of Dermatology, University Medical Center Regensburg, 93042, Regensburg, Germany
| | - T. Maisch
- Department of Dermatology, University Medical Center Regensburg, 93042, Regensburg, Germany
| | - S. Karrer
- Department of Dermatology, University Medical Center Regensburg, 93042, Regensburg, Germany
| | - D. Niebel
- Department of Dermatology, University Medical Center Regensburg, 93042, Regensburg, Germany
| | - M. Berneburg
- Department of Dermatology, University Medical Center Regensburg, 93042, Regensburg, Germany
| | - B. Kurz
- Department of Dermatology, University Medical Center Regensburg, 93042, Regensburg, Germany
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Orozco J, Nguyen J, Yasrebi SM, Blalock M, Grisales SL, Jensen CL, DeGuzman MM. Severe gastrointestinal manifestations in childhood-onset lupus: A single-center cohort and review of the literature. Lupus 2025:9612033251345020. [PMID: 40398633 DOI: 10.1177/09612033251345020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/23/2025]
Abstract
ObjectiveSystemic lupus erythematosus (SLE) is a complex autoimmune condition with diverse manifestations. Childhood-onset SLE (cSLE) presents more severely than adult-onset disease with a higher incidence of severe neurologic or renal manifestations and lower estimated survival rates. There is limited literature on the range of severe gastrointestinal manifestations at presentation in cSLE, and this lack of information results in underappreciation of these potentially life-threatening complications and little guidance regarding management of these patients.MethodsWe reviewed cases of patients with cSLE and severe GI manifestations at presentation diagnosed at our institution and additionally provide a comprehensive review of existing cases in the literature to discuss presenting symptoms, other clinical features, longitudinal course, treatment, and long-term outcomes.ResultsWe identified six cases of cSLE with primary, severe GI symptoms at time of diagnosis at our institution and an additional 25 patients who presented similarly in the literature. Severe GI manifestations included protein-losing enteropathy, thoracoabdominal aortitis, severe pancreatitis, lupus enteritis or mesenteric vasculitis, and intestinal pseudo-obstruction. Delays in diagnosis affected several patients, and 26% of patients required surgical intervention. Many patients required intensive immunomodulatory treatment in addition to prolonged bowel rest and parenteral nutrition. Long-term outcomes of GI manifestations varied overall, however, most patients at our institution achieved clinical remission.ConclusionsUnderstanding these rare cases of severe GI manifestations in cSLE can aid clinicians in prompt diagnosis and collaborative management, improving clinical outcomes for this vulnerable population.
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Affiliation(s)
- James Orozco
- Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
- Division of Pediatric Gastroenterology, Boston Children's Hospital, Boston, MA, USA
| | - Jessica Nguyen
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
- Division of Pediatric Rheumatology, Texas Children's Hospital, Houston, TX, USA
| | - Sara Mm Yasrebi
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - Marnie Blalock
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - Sara L Grisales
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - Craig L Jensen
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
- Division of Pediatric Gastroenterology, Texas Children's Hospital, Houston, TX, USA
| | - Marietta M DeGuzman
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
- Division of Pediatric Rheumatology, Texas Children's Hospital, Houston, TX, USA
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Radhakrishnan S, Gowthuvalli Venkataramana C, Mahabala C, Varadanayakanahalli MB. Diagnostic pitfall: Castleman's disease versus systemic lupus erythematosus in a woman with generalised lymphadenopathy. BMJ Case Rep 2025; 18:e264605. [PMID: 40404200 DOI: 10.1136/bcr-2024-264605] [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: 05/24/2025] Open
Abstract
Systemic lupus erythematosus is an autoimmune disease with diverse systemic manifestations, while Castleman disease is a rare lymphoproliferative disorder that often presents with systemic symptoms and can mimic autoimmune disorders. β-thalassaemia trait is a genetic disorder characterised by mild anaemia. We report the case of a young female who presented with febrile episodes persisting for 6 months, accompanied by multiple joint pain and left-sided chest pain for 3 months. Physical examination revealed pallor, generalised lymphadenopathy, splenomegaly and left-sided pleural effusion. Lymph node biopsy initially suggested Castleman disease-hyaline vascular variant. However, further evaluation led to a final diagnosis of systemic lupus erythematosus with lupus nephritis and concomitant β-thalassaemia trait. This case highlights the diagnostic challenge when multiple diseases with overlapping symptoms coexist and the importance of a comprehensive evaluation in patients with atypical presentations to avoid diagnostic overshadowing.
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Affiliation(s)
- Shalini Radhakrishnan
- Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | | | - Chakrapani Mahabala
- Department of General Medicine, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, India
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Huang W, Dong J, Luo S, Zhang J, Zhang L, Ma Y, Wang B, Wang J, Dou W, Qi L, Hu W, Zhang L. Cardiac magnetic resonance feature tracking evaluates left atrial strain in patients with systemic lupus erythematosus and mitral regurgitation. Lupus 2025:9612033251344983. [PMID: 40391525 DOI: 10.1177/09612033251344983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/21/2025]
Abstract
PurposeTo explore left atrial (LA) function in patients with systemic lupus erythematosus (SLE) and mitral regurgitation assessed by cardiac magnetic resonance imaging feature tracking (MRI-FT).MethodIn this study, 64 SLE patients (35.0 ± 12.3 years, 49 females) and 50 age- and gender-matched healthy controls (32.1 ± 11.2 years, 32 females) were analyzed. Patients with SLE were further classified into two subgroups according to mitral regurgitation defined by echocardiography: mitral regurgitation subgroup (n = 32) and non-mitral regurgitation subgroup (n = 32). All subjects underwent cardiac magnetic resonance (CMR) examination and SLE patients underwent extra laboratory testing. LA volume and strain parameters were compared among the three groups, and a correlation analysis was further performed between CMR parameters and clinical variables.ResultsPatients in both mitral regurgitation and non-mitral regurgitation subgroups showed higher LAVmin (29.15 ± 7.5, 26.22 ± 8.23 vs 21.68 ± 7.67, p = .003, .026) and LAVimin (17.44,14.9 vs 12.62, p = .002,.046) than healthy control subjects. Abnormal LA reservoir, conduit and bump strain were also observed in SLE patients (all p < .05), with more severe reservoir (p = .006, .031) and bump strain (p = .01, .033) abnormality found in mitral regurgitation subgroup. In the SLE group, LA reservoir, bump and conduit strain were significantly positively correlated with LVEF (B = 0.467, p < .001 vs B = 0.019, p = .01 vs B = 0.168, p = .001 vs B = 0.036, p < .001 vs B = 0.020, p = .024). Conduit strain (εe, SRe) was positively correlated with LAEF (B = 0.229, p = .032 vs B = 0.027, p = .008).ConclusionMRI-FT based LA parameters may be considered a helpful tool to evaluate LA function in SLE patients, and LA strain may indicate severity of the cardiac dysfunction in SLE patients.
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Affiliation(s)
- Weiwei Huang
- Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Jianhua Dong
- National Clinical Research Center of Kidney Disease, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Song Luo
- Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Jun Zhang
- Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Lingyan Zhang
- Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Yan Ma
- Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Bin Wang
- Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Jingxin Wang
- Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | | | - Li Qi
- Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Weixin Hu
- National Clinical Research Center of Kidney Disease, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Longjiang Zhang
- Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
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Lu RL, Chen YR, Yang XF, Huang XY, Liu DZ, Hong XP. Genetic liability to gut microbiota and inflammatory cytokines in relation to systemic lupus erythematosus risk: a multi-omics study. Clin Rheumatol 2025:10.1007/s10067-025-07435-7. [PMID: 40332703 DOI: 10.1007/s10067-025-07435-7] [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: 12/17/2024] [Revised: 03/28/2025] [Accepted: 04/07/2025] [Indexed: 05/08/2025]
Abstract
OBJECTIVES Systemic lupus erythematosus (SLE) has been associated with gut microbiota in some studies. There is no clear evidence that cytokines act as mediators. METHODS We first assessed the differences in gut microbiota between SLE patients and healthy controls using 16S rDNA sequencing. Subsequently, we used the summary statistics of gut microbiota, cytokines, and SLE from large genome-wide association studies. To explore the causal relationships between gut microbiota and SLE and identify potential mediating cytokines, we performed bidirectional Mendelian randomization analyses. Finally, the levels of potentially mediating cytokines were determined by ELISA. RESULTS Fecal 16S rDNA sequencing showed that there was gut microbiota disorder in SLE patients. Based on two-sample analysis, seven gut microbiota taxa were causally associated with SLE. SLE influenced the relative abundance of two gut microbiota taxa in our large-scale MR study. Mediation analyses revealed that the causal relationship between genus Lachnospiraceae UCG001 and SLE was exclusively mediated by fibroblast growth factor 19 (FGF19) levels and the causal relationship between order Lactobacillales and SLE was exclusively mediated by tumor necrosis factor receptor superfamily member 9 (TNFRSF9) levels. Elevated levels of FGF19 affected the association between the reduced relative abundance of the genus Coprobacter and SLE, mediating by a proportion of 10.64% (P = 0.030). Furthermore, ELISA showed that circulating TNFRSF9 and FGF19 levels were higher in SLE patients than healthy controls. CONCLUSION Our study demonstrated that there is a causal link between some gut microbiota taxa and SLE. In addition, we revealed possible mediating effects in this relationship. Key Points • We first demonstrate a causal association between gut microbiota, cytokines, and SLE comprehensively. • Our experiments also confirmed that TNFRSF9 and FGF19 may play a role in SLE. These results provide new ideas for microbiome-based investigation of new mechanisms and therapies for SLE.
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Affiliation(s)
- Rui-Ling Lu
- Department of Rheumatology and Immunology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China
| | - Yan-Ran Chen
- Department of Rheumatology and Immunology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China
| | - Xu-Fa Yang
- Department of Rheumatology and Immunology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
| | - Xin-Yi Huang
- Department of Rheumatology and Immunology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
| | - Dong-Zhou Liu
- Department of Rheumatology and Immunology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
- Department of Rheumatology and Immunology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.
| | - Xiao-Ping Hong
- Department of Rheumatology and Immunology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
- Department of Rheumatology and Immunology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.
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Yang P, Liu Q, Zhang H, Wu M, Zhao J, Shen G, Zhao Y. Risk relationship between six autoimmune diseases and malignancies: An umbrella review. Autoimmun Rev 2025; 24:103779. [PMID: 39983807 DOI: 10.1016/j.autrev.2025.103779] [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: 09/20/2024] [Revised: 02/12/2025] [Accepted: 02/14/2025] [Indexed: 02/23/2025]
Abstract
BACKGROUND The bidirectional relationship between autoimmune diseases and malignancy has been widely discussed. And the relationship between autoimmune diseases and the risk of malignancy varies. Here, we categorized and re-analyzed the evidence of the association between six autoimmune diseases and malignancy risk, in order to provide ideas for the prevention of malignancy in the long-term individualized management of patients with autoimmune diseases. METHODS We systematically searched the relevant literatures in PubMed, Web of Science and Cochrane Library to identify and re-analyze studies methodically on the association between six autoimmune diseases and their malignancy risk. Our results showed that. RESULTS We included 34 meta-analyses including systematic lupus erythematosus, rheumatoid arthritis, psoriasis, ankylosing spondylitis, primary Sjogren's syndrome, multiple sclerosis, totalling 742 studies. Our results showed that the remaining five AIDs, with the exception of MS, were positively associated with the risk of overall malignancy. Among them, patients with SLE had the highest risk of developing lymphomas, oropharyngeal cancer and non-Hodgkin's lymphoma, and the lowest risk of developing uterine cancer, melanoma and endometrial cancer. The RA patients had the highest risk of developing lymphomas, Hodgkin's lymphoma and non-Hodgkin's and the lowest risk of colon cancer. pSS patients had the highest risk of lymphoma. MS patients had the highest risk of lung cancer and the lowest risk of testicular cancer. AS patients had the highest risk of lymphoblastic leukemia. PsO patients had the highest risk of keratinocyte cancer. CONCLUSION Patients with systematic lupus erythematosus, rheumatoid arthritis, psoriasis, ankylosing spondylitis and primary Sjogren's syndrome lead to an increased risk of overall malignancy, whereas patients with MS lead to a decreased risk of overall malignancy. However, the risk relationship between the same AIDs and different malignancies varied.
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Affiliation(s)
- Ping Yang
- Qinghai University, China; The Center of Breast Disease Diagnosis and Treatment of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining 810000, China
| | | | - Hengheng Zhang
- Qinghai University, China; The Center of Breast Disease Diagnosis and Treatment of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining 810000, China
| | - Meijie Wu
- Qinghai University, China; The Center of Breast Disease Diagnosis and Treatment of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining 810000, China
| | - Jiuda Zhao
- The Center of Breast Disease Diagnosis and Treatment of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining 810000, China
| | - Guoshuang Shen
- The Center of Breast Disease Diagnosis and Treatment of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining 810000, China
| | - Yi Zhao
- The Center of Breast Disease Diagnosis and Treatment of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining 810000, China.
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Alexander T, Sewerin P, Strangfeld A, Schulte M, Borchert J, Garcia TB, Schrom E. Real-World Prevalence, Incidence and Management of Systemic Lupus Erythematosus in Germany: A Retrospective Claims Data Analysis. Rheumatol Ther 2025; 12:237-254. [PMID: 39776056 PMCID: PMC11920567 DOI: 10.1007/s40744-024-00735-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 12/06/2024] [Indexed: 01/11/2025] Open
Abstract
INTRODUCTION This study evaluated the prevalence and incidence of systemic lupus erythematosus (SLE) in Germany and explored real-world data on sequence of therapy (SOT; sequence of drugs as prescribed in clinical practice). METHODS This retrospective, observational, longitudinal cohort study using German claims data from the WIG2 GmbH Scientific Institute for Health Economics and Health System Research database (January 2011-December 2019), extrapolated to the statutory health insurance (SHI)-insured population, evaluated prevalence and incidence in an epidemiological analysis group and SLE treatment patterns in an incident cohort (subgroup ≥ 18 years of age with incident disease and ≥ 24-month follow-up post index date). Analyses were descriptive. RESULTS Based on the epidemiological analysis (N = 3017), annual SLE prevalence per 100,000 gradually increased from 40.47 in 2012 to 59.87 in 2019 in the SHI population. In contrast, annual SLE incidence was relatively stable, ranging from 8.83 in 2012 to 8.86 in 2019. In the incident cohort (n = 941), based on SOT analysis (n = 681), treatment gaps of > 60 days were common: 67.1%, 51.2% and 54.9% in SOT1, SOT2 and SOT3, respectively. Corticosteroids were the most frequent monotherapy in SOT1 (31.0% vs 0% in SOT2/SOT3); 30.0-70.0% of patients received a corticosteroid combination therapy across SOTs. Over 50% of patients in each SOT received an antimalarial therapy (combination or monotherapies). The use of biologic disease-modifying drugs was low, ranging from 0.4% in SOT1 to 9.7% in SOT3. CONCLUSIONS Our data demonstrate an increased prevalence of SLE with stable incidence in Germany, suggesting improved survival of affected patients. Nevertheless, suboptimal treatment patterns, including limited use of biologics, reflect a high unmet need for optimised and personalised therapies in patients with SLE.
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Affiliation(s)
- Tobias Alexander
- Charité, Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Berlin, Germany.
| | - Philipp Sewerin
- Department and Hiller Research Unit for Rheumatology, UKD, Heinrich-Heine University, Düsseldorf, Germany
- Ruhr-University Bochum, Rheumazentrum Ruhrgebiet, Herne, Germany
| | - Anja Strangfeld
- Charité, Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Berlin, Germany
- Epidemiology and Health Services Research, German Rheumatism Research Center (DRFZ Berlin), Berlin, Germany
| | | | - Julia Borchert
- WIG2 GmbH Scientific Institute for Health Economics and Health System Research, Leipzig, Germany
| | - Tarcyane Barata Garcia
- WIG2 GmbH Scientific Institute for Health Economics and Health System Research, Leipzig, Germany
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Cheng C, Li B, Li J, Wang Y, Xiao H, Lian X, Chen L, Wang J, Wang H, Qin S, Yu L, Wu T, Peng S, Tan W, Ye Q, Chen W, Jiang X. Multi-stain deep learning prediction model of treatment response in lupus nephritis based on renal histopathology. Kidney Int 2025; 107:714-727. [PMID: 39733792 DOI: 10.1016/j.kint.2024.12.007] [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: 02/06/2024] [Revised: 10/03/2024] [Accepted: 12/16/2024] [Indexed: 12/31/2024]
Abstract
The response of the kidney after induction treatment is one of the determinants of prognosis in lupus nephritis, but effective predictive tools are lacking. Here, we sought to apply deep learning approaches on kidney biopsies for treatment response prediction in lupus nephritis. Patients who received cyclophosphamide or mycophenolate mofetil as induction treatment were included, and the primary outcome was 12-month treatment response, complete response defined as 24-h urinary protein under 0.5 g with normal estimated glomerular filtration rate or within 10% of normal range. The model development cohort included 245 patients (880 digital slides), and the external test cohort had 71 patients (258 digital slides). Deep learning models were trained independently on hematoxylin and eosin-, periodic acid-Schiff-, periodic Schiff-methenamine silver- and Masson's trichrome-stained slides at multiple magnifications and integrated to predict the primary outcome of complete response to therapy at 12 months. Single-stain models showed area under the curves of 0.813, 0.841, 0.823, and 0.862, respectively. Further, integration of the four models into a multi-stain model achieved area under the curves of 0.901 and 0.840 on internal validation and external testing, respectively, which outperformed conventional clinicopathologic parameters including estimated glomerular filtration rate, chronicity index and reduction in proteinuria at three months. Decisive features uncovered by visualization for model prediction included tertiary lymphoid structures, glomerulosclerosis, interstitial fibrosis and tubular atrophy. Our study demonstrated the feasibility of utilizing deep learning on kidney pathology to predict treatment response for lupus patients. Further validation is required before the model could be implemented for risk stratification and to aid in making therapeutic decisions in clinical practice.
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Affiliation(s)
- Cheng Cheng
- Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Bin Li
- Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jie Li
- Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yiqin Wang
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; National Health Commission Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, Guangdong, China
| | - Han Xiao
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xingji Lian
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; National Health Commission Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, Guangdong, China
| | - Lizhi Chen
- Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Junxian Wang
- Department of Nephrology, Zhongshan City People's Hospital, Zhongshan, Guangdong, China
| | - Haiyan Wang
- Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Shuguang Qin
- Department of Nephrology, Guangzhou First People's Hospital, Guangzhou, Guangdong, China
| | - Li Yu
- Department of Pediatrics, Guangzhou First People's Hospital, Guangzhou, Guangdong, China
| | - Tingbo Wu
- Department of Pediatrics, Zhongshan City People's Hospital, Zhongshan, Guangdong, China
| | - Sui Peng
- Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Department of Gastroenterology and Hepatology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Weiping Tan
- Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
| | - Qing Ye
- Department of Nephrology, Zhongshan City People's Hospital, Zhongshan, Guangdong, China.
| | - Wei Chen
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China; National Health Commission Key Laboratory of Clinical Nephrology (Sun Yat-sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, Guangdong, China.
| | - Xiaoyun Jiang
- Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
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Huo R, Wei C, Yang Y, Lin J, Huang X. Hydroxychloroquine: A double‑edged sword (Review). Mol Med Rep 2025; 31:102. [PMID: 39981928 PMCID: PMC11868775 DOI: 10.3892/mmr.2025.13467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 01/14/2025] [Indexed: 02/22/2025] Open
Abstract
Hydroxychloroquine (HCQ) is an antimalarial drug that has historically been used to treat and prevent malaria. However, its mechanism of action has not yet been fully elucidated. HCQ affects various cellular and molecular pathways through different mechanisms. HCQ has also been shown to be a disease‑improving agent for the treatment of rheumatic diseases, including systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis and primary Sjögren's syndrome. Although generally considered safe, adverse reactions have been reported with the use of HCQ and clinicians should carefully monitor patients with rheumatism when prescribing these drugs. The purpose of the present review is to strengthen the clinical use of HCQ for autoimmune diseases while highlighting the adverse effects that may occur during treatment.
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Affiliation(s)
- Rongxiu Huo
- Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530016, P.R. China
| | - Chengcheng Wei
- Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530016, P.R. China
| | - Yanting Yang
- Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530016, P.R. China
| | - Jinying Lin
- Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530016, P.R. China
| | - Xinxiang Huang
- Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530016, P.R. China
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Qin Q, Wang Y, Yan S, Qu G, Li Y, Zhang C, Bai Y, Wang D, Luo S, Li B, Han Y, Chen W, Zhen Q, Sun L. Study on the Correlation Between Double-Stranded DNA and Systemic Lupus Erythematosus. Exp Dermatol 2025; 34:e70102. [PMID: 40243281 DOI: 10.1111/exd.70102] [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: 03/27/2024] [Revised: 04/01/2025] [Accepted: 04/06/2025] [Indexed: 04/18/2025]
Abstract
Circulating cell-free DNA (cfDNA) is a large molecule that plays a central role in the pathogenesis of SLE. It is the target antigen of autoantibodies and the main component of immune complexes. Due to the large differences in the content of cfDNA detected in different studies, cfDNA cannot be used as a strong diagnostic basis for SLE at present. As an active component of cfDNA, the correlation between double-stranded DNA (dsDNA) and SLE has not been fully studied. The detection of dsDNA may provide a more accurate diagnosis and treatment basis for SLE, and the in-depth study of SLE patients is helpful to further understand the pathogenesis of SLE. Blood samples were collected from 173 SLE patients and 2970 healthy controls. The concentration of serum dsDNA was determined by fluorescence quantitative method. Propensity score matching (PSM) method was used to match 444 healthy controls and 148 SLE patients according to age and gender. Serum dsDNA levels were compared between SLE patients and matched healthy controls. At the same time, blood exosomes were extracted to explore the correlation between serum dsDNA and exosome dsDNA. As demonstrated herein, serum dsDNA levels in SLE patients were shown to be considerably higher than in healthy controls. Meanwhile, In SLE patients, serum dsDNA level was correlated with season and other clinical indicators, but not with temperature and ultraviolet. Additionally, a statistically significant connection between serum and exosome dsDNA was discovered. We also found that the gene encoding the dsDNA receptor was upregulated. The presented data suggest that detection of dsDNA is promising as a rapid and simple tool for assessing disease progression in SLE, which can help physicians and patients in disease management. The mechanism of elevated dsDNA in SLE patients requires more research.
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Affiliation(s)
- Qin Qin
- Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China
| | - Yirui Wang
- Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China
| | - Sihao Yan
- Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China
| | - Guangbo Qu
- Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China
| | - Yuanyuan Li
- Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China
| | - Chang Zhang
- Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China
| | - Yuanming Bai
- Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China
| | - Daiyue Wang
- Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China
| | - Sihan Luo
- Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China
| | - Bao Li
- Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- The Comprehensive Lab, College of Basic Medicine, Anhui Medical University, Hefei, China
| | - Yang Han
- North China University of Science and Technology Affiliated Hospital, Thangshan, China
- Health Science Center, North China University of Science and Technology, Tangshan, China
- Inflammation and Immune Diseases Laboratory of North China University of Science and Technology, Tangshan, China
| | - Weiwei Chen
- Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China
| | - Qi Zhen
- North China University of Science and Technology Affiliated Hospital, Thangshan, China
- Health Science Center, North China University of Science and Technology, Tangshan, China
- Inflammation and Immune Diseases Laboratory of North China University of Science and Technology, Tangshan, China
| | - Liangdan Sun
- Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China
- Health Science Center, North China University of Science and Technology, Tangshan, China
- Inflammation and Immune Diseases Laboratory of North China University of Science and Technology, Tangshan, China
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Carvalho C, Rocha APR, Dos Santos GB, Guimarães JB, Amorim MN, Beleza ACS, Rodrigues-de-Souza DP, da Silva Serrão PRM, de Oliveira Sato T. Pelvic Floor Dysfunction and Associated Factors in Women with Systemic Autoimmune Rheumatic Diseases: A Cross-Sectional Study. Int Urogynecol J 2025; 36:821-828. [PMID: 39903236 DOI: 10.1007/s00192-025-06071-8] [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: 10/01/2024] [Accepted: 01/14/2025] [Indexed: 02/06/2025]
Abstract
INTRODUCTION AND HYPOTHESIS Systemic autoimmune rheumatic diseases (SARDs) cause musculoskeletal disorders and are associated with various issues that affect the quality of life. Since the musculoskeletal system is affected, the pelvic floor muscles can also be impacted, leading to possible pelvic floor dysfunctions (PFDs). Thus, the purpose of this study was to investigate the presence of PFDs, such as urinary incontinence (UI), anal incontinence (AI), genital-pelvic pain/penetration disorder (GPPPD), and pelvic organ prolapse (POP) symptoms in women with SARDs compared to a control group composed of women without SARDs; and investigate the association between SARDs and PFDs. METHODS An online cross-sectional survey was carried out. Using a web-based questionnaire, data on demographic and anthropometric features, PFD (UI, nocturia, AI, GPPPD, and POP), and obstetric history were gathered. For quantitative variables, the Mann-Whitney U test was used, and for categorical variables, the chi-squared test was used for comparison between groups. The association between SARDs and PFD was investigated using logistic regression analysis. RESULTS The questionnaire was completed by 326 women (224 with SARDs and 102 healthy controls). Women with SARDs reported significantly more symptoms of PFD, UI, nocturia, AI (flatus and fecal incontinence), POP, and GPPPD than healthy controls. SARDs were associated with PFD, flatus incontinence, fecal incontinence, dyspareunia, and vaginismus. CONCLUSIONS PFD was much more common in women with SARDs than in healthy women. Women with SARDs were 1.8 to 5.2 times more likely than the control group to report PFD symptoms than women without SARDs.
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Affiliation(s)
- Cristiano Carvalho
- Department of Biosciences, Federal University of São Paulo, Campus Baixada Santista, Rua Silva Jardim, 136, Santos, SP, 11015-020, Brazil.
- Department of Physical Therapy, Federal University of São Carlos, São Carlos, SP, Brazil.
| | | | | | - Júlia Barbosa Guimarães
- Department of Biosciences, Federal University of São Paulo, Campus Baixada Santista, Rua Silva Jardim, 136, Santos, SP, 11015-020, Brazil
| | - Mariana Nobrega Amorim
- Department of Biosciences, Federal University of São Paulo, Campus Baixada Santista, Rua Silva Jardim, 136, Santos, SP, 11015-020, Brazil
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12
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Yu H, Ma Z, Su S, Xu Z, Yi H. RNA modification: a promising code to unravel the puzzle of autoimmune diseases and CD4 + T cell differentiation. Front Immunol 2025; 16:1563150. [PMID: 40196109 PMCID: PMC11973318 DOI: 10.3389/fimmu.2025.1563150] [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: 01/19/2025] [Accepted: 03/06/2025] [Indexed: 04/09/2025] Open
Abstract
Dynamic changes in various forms of RNA modification are critical to the functional homeostasis of the immune system and the pathophysiology of autoimmune diseases. RNA modification-related proteins play an essential role in these processes. At present, the research methods of RNA modification in autoimmune diseases are mainly to detect the expression changes of RNA modification-related proteins in tissues or cells, but there is a lack of explorations of target RNAs and in-depth mechanisms. Considering the important role of CD4+ T cell dysfunction in the pathogenesis and progression of autoimmune diseases, the regulatory effect of abnormal RNA modification on CD4+ T cells deserves attention, which will provide a perspective for further exploring the mechanism of RNA modification in autoimmune diseases. In this Review, we discuss the abnormal RNA modification changes in patients with autoimmune diseases and highlight the effects of these abnormal changes on CD4+ T cells.
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Affiliation(s)
- Hui Yu
- Central Laboratory, The First Hospital of Jilin University, Changchun, Jilin, China
- Key Laboratory of Organ Regeneration and Transplantation, Ministry of Education, Changchun, Jilin, China
| | - Zhanchuan Ma
- Central Laboratory, The First Hospital of Jilin University, Changchun, Jilin, China
- Key Laboratory of Organ Regeneration and Transplantation, Ministry of Education, Changchun, Jilin, China
| | - Sensen Su
- Central Laboratory, The First Hospital of Jilin University, Changchun, Jilin, China
- Key Laboratory of Organ Regeneration and Transplantation, Ministry of Education, Changchun, Jilin, China
| | - Zheng Xu
- Department of Cardiology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Huanfa Yi
- Central Laboratory, The First Hospital of Jilin University, Changchun, Jilin, China
- Key Laboratory of Organ Regeneration and Transplantation, Ministry of Education, Changchun, Jilin, China
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13
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Chapuis E, Moussi F, Dossier A, Rio J, Mageau A, Sacre K. Hospital admission from the emergency department of adult patients affected by immune-mediated inflammatory diseases: a multidimensional retrospective analysis of an hospital-based cohort. Intern Emerg Med 2025:10.1007/s11739-025-03899-2. [PMID: 40029568 DOI: 10.1007/s11739-025-03899-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 02/10/2025] [Indexed: 03/05/2025]
Affiliation(s)
- Elisa Chapuis
- Service de Médecine Interne, Hôpital Bichat, Université Paris Cité, Assistance Publique Hôpitaux de Paris, 46 Rue Henri Huchard, 75018, Paris, France
| | - Fetta Moussi
- Service de Médecine Interne, Hôpital Bichat, Université Paris Cité, Assistance Publique Hôpitaux de Paris, 46 Rue Henri Huchard, 75018, Paris, France
| | - Antoine Dossier
- Service de Médecine Interne, Hôpital Bichat, Université Paris Cité, Assistance Publique Hôpitaux de Paris, 46 Rue Henri Huchard, 75018, Paris, France
| | - Julien Rio
- Département de l'Information Médicale, Hôpital Bichat, Université Paris Cité, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Arthur Mageau
- Service de Médecine Interne, Hôpital Bichat, Université Paris Cité, Assistance Publique Hôpitaux de Paris, 46 Rue Henri Huchard, 75018, Paris, France
| | - Karim Sacre
- Service de Médecine Interne, Hôpital Bichat, Université Paris Cité, Assistance Publique Hôpitaux de Paris, 46 Rue Henri Huchard, 75018, Paris, France.
- Centre de Recherche sur l'Inflammation, Laboratoire d'Excellence Inflamex, INSERM UMR 1149, Paris, France.
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14
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Dong Z, Luo P, Sun S, Ni Z, He Y, Huang X, Liu Z, Wu Z, Zhang X, Liao Y, Zhao J, Lin H, Zhang X, Fu R, Ding G, Xu Y, Wang L, Xiao Y, Shi S, Zuo X, Li Z, Qiao L, Wang R, Li W, Wan J, Li Y, Guan T, Deng X, Wu X, Zheng H, Chen J, He L, Yamaguchi S, Wang H, Cai GY, Zhang L, Chen X. Mizoribine or Cyclophosphamide for Lupus Nephritis: A Randomized Clinical Trial. JAMA Netw Open 2025; 8:e250648. [PMID: 40085084 PMCID: PMC11909609 DOI: 10.1001/jamanetworkopen.2025.0648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Accepted: 01/08/2025] [Indexed: 03/16/2025] Open
Abstract
Importance Lupus nephritis is typically treated with intravenous cyclophosphamide, which is associated with serious adverse effects. Oral mizoribine may be an alternative for induction therapy of lupus nephritis. However, large-scale, long-term, randomized clinical studies of mizoribine are lacking. Objective To assess the efficacy and safety of oral mizoribine vs intravenous cyclophosphamide as induction therapy for Chinese patients with lupus nephritis. Design, Setting, and Participants This prospective, multicenter, parallel-group, open-label, phase 3 randomized clinical trial recruited patients with class III, III+V, IV, IV+V, or V lupus nephritis aged 18 to 70 years from 40 centers in China. Inclusion criteria included 24-hour urinary protein level of 1.0 g or higher and systemic lupus erythematosus disease activity index of 8 or higher. The first patient was enrolled on November 29, 2014, and the study finished March 14, 2019. The follow-up period was 52 weeks. Data were analyzed from September 4, 2019, to January 21, 2020. Interventions Oral mizoribine (50 mg, 3 times a day) or cyclophosphamide (6 intravenous doses at 0.5-1.0 g/m2 body surface area, with a maximum dose of 1.0 g/d) for 52 weeks plus oral glucocorticoid. Main Outcomes and Measures Total remission rate (complete remission rate plus partial remission rate) after 52 weeks (prespecified). Results A total of 250 patients were randomized, and 243 patients (mean [SD] age, 34.6 [10.7] years, 213 women [87.7%]) were treated (123 patients [50.6%] in the mizoribine group and 120 patients [49.4%] in the cyclophosphamide group). The total remission rate at 52 weeks was 66.1% (76 of 115 patients) in the mizoribine group and 76.8% (86 of 112 patients) in the cyclophosphamide group, and the relative risk ratio (mizoribine vs cyclophosphamide) was 0.861 (95% CI, 0.729-1.016). The lower limit of this 2-sided 95% CI was greater than the noninferiority margin of 0.726, indicating that mizoribine was noninferior to cyclophosphamide. Changes in other immune parameters and kidney function were generally similar between the groups. The incidence of any treatment-related treatment-emergent adverse events was 80.5% (99 of 123 patients) in the mizoribine group and 78.7% (96 of 122 patients) in the cyclophosphamide group, and the most frequent adverse event in both groups was upper respiratory tract infection (41 patients [33.3%] and 37 patients [30.3%], respectively). Conclusions and Relevance This randomized clinical trial shows that compared with intravenous cyclophosphamide, oral mizoribine was noninferior and well tolerated when used with glucocorticoid for induction therapy of active lupus nephritis. Mizoribine can be used as an alternative to intravenous cyclophosphamide as induction therapy for lupus nephritis. Trial Registration ClinicalTrials.gov Identifier: NCT02256150.
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Affiliation(s)
- Zheyi Dong
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
| | - Ping Luo
- Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Shiren Sun
- Department of Nephrology, The First Affiliated Hospital of Air Force Medical University of PLA, Xi’an, Shaanxi, China
| | - Zhaohui Ni
- Department of Nephrology, Renji Hospital Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yani He
- Department of Nephrology, Army Medical Center of PLA, Beijing, China
| | - Xiangyang Huang
- Department of Nephrology, Liuzhou Worker’s Hospital, Liuzhou, Guanxi, China
| | - Zhangsuo Liu
- Research Institute of Nephrology, Zhengzhou University, Zhengzhou, Henan, China
| | - Zhenbiao Wu
- Department of Clinical Immunology, Xijing Hospital, Air Force Medical University (Fourth Military Medical University), Xi’an, Shaanxi, China
| | - Xinzhou Zhang
- Department of Nephrology, Shenzhen People’s Hospital, Shenzhen, Guandong, China
| | - Yunhua Liao
- Department of Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Jianhong Zhao
- Department of Immunology, Jining First People’s Hospital, Jining, Shandong, China
| | - Hongli Lin
- Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Xiao Zhang
- Department of Rheumatism and Immunology, Guangdong Provincial People’s Hospital, Guangzhou, Guangdong, China
| | - Rongguo Fu
- Department of Nephrology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Guohua Ding
- Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yan Xu
- Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Lihua Wang
- Department of Nephrology, Shanxi Medical University Second Hospital, Taiyuan, Shanxi, China
| | - Yuefei Xiao
- Department of Nephrology and Rheumatology, Aerospace Center Hospital, Beijing, China
| | - Shumei Shi
- Department of Nephrology, The 960th Hospital of PLA Joint Logistics Support Force, Jinan, Shandong, China
| | - Xiaoxia Zuo
- Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhanguo Li
- Department of Rheumatism and Immunology, Peking University People’s Hospital, Beijing, China
| | - Li Qiao
- Department of Nephrology, The 920th Hospital of PLA Joint Logistics Support Force, Kunming, Yunnan, China
| | - Rong Wang
- Department of Nephrology, Shandong Provincial Hospital, Jinan, Shandong, China
| | - Wenge Li
- Department of Nephrology, China-Japan Friendship Hospital, Beijing, China
| | - Jianxin Wan
- Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China
| | - Ying Li
- Department of Nephrology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | - Tianjun Guan
- Department of Nephrology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, China
| | - Xiaoli Deng
- Department of Immunology, Peking University Third Hospital, Beijing, China
| | - Xiaoyan Wu
- Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Hongguang Zheng
- Department of Nephrology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Jianghua Chen
- Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Shangcheng, Hangzhou, Zhejiang, China
| | - Lan He
- Department of Rheumatism, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | | | - Hua Wang
- Asahi Kasei Pharma (Beijing) Co, Ltd, Beijing, China
| | - Guang-yan Cai
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
| | - Li Zhang
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
| | - Xiangmei Chen
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China
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15
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Duremala F, Tiniakou E, Andrews J. Epidemiology of myositis. Curr Opin Rheumatol 2025; 37:121-127. [PMID: 39655458 DOI: 10.1097/bor.0000000000001076] [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: 01/30/2025]
Abstract
PURPOSE OF REVIEW This review aims to synthesize recent developments in the epidemiology of idiopathic inflammatory myopathies (IIMs), focusing on incidence, prevalence, disease classification, and clinical outcomes. RECENT FINDINGS IIM is a rare group of autoimmune diseases characterized by muscle weakness and systemic involvement, with incidence rates ranging from 0.2 to 2 cases per 100 000 person-years. The role of myositis-specific autoantibodies (MSAs) in stratifying disease risk and prognosis is increasingly recognized, such as in anti-MDA5 positive DM, which is associated with a high risk of rapidly progressive interstitial lung disease. Furthermore, patients with IIM exhibit elevated risks of comorbidities, including cardiovascular disease and malignancy. SUMMARY IIM diseases are complex disorders with significant health impacts, necessitating enhanced awareness and research. Improved classification and understanding of MSAs are crucial for earlier diagnosis and tailored therapeutic strategies. Continued epidemiological research is essential to elucidate underlying mechanisms and inform future interventions, ultimately aiming to enhance the quality of life and clinical outcomes for affected patients.
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Affiliation(s)
- Fnu Duremala
- Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Alabama
| | - Eleni Tiniakou
- Division of Rheumatology Medicine, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - James Andrews
- Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Alabama
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Liu T, Yang M, Feng X, Zou X, Xia Y, Chen L, Gao Z, Zhao L, Wang X. Unraveling the role of lncRNAs and their associated nearby coding genes in the pathogenesis of systemic lupus erythematosus. Arthritis Res Ther 2025; 27:44. [PMID: 40025620 PMCID: PMC11871770 DOI: 10.1186/s13075-025-03510-1] [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: 05/07/2024] [Accepted: 02/18/2025] [Indexed: 03/04/2025] Open
Abstract
BACKGROUND The role of long non-coding RNAs (lncRNAs) and their nearby messenger RNAs (mRNAs) in systemic lupus erythematosus (SLE) pathogenesis is not well understood. METHOD High-throughput sequencing was utilized to analyze PBMCs obtained from SLE patients. Subsequently, we conducted differential analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and verification through quantitative real-time PCR (qRT-PCR). Additionally, qRT-PCR was used to analyze the levels of lncRNAs or mRNAs in transfected Raji cells. RESULTS We identified 419 differentially expressed (DE) lncRNAs and their 337 nearby DE mRNAs in SLE patients. More than 67% of the DE lncRNAs were lincRNAs and intronic_lncRNAs. The most significantly regulated nearby mRNAs in SLE patients were LTF and CIRBP, potentially involved in recurrent infection and photosensitivity. GO analysis revealed upregulation of the immune effector process term, with genes such as C1qA, C1qC, C1qB, NLRP3, and CXCL6 participating in this term and the upregulated pertussis signaling pathway. Analysis of the nearby coding genes of 88 lincRNAs indicated that XLOC_185773 had the highest number of nearby encoding genes and was negatively correlated with peripheral blood lymphocyte counts, potentially regulating HARS. Furthermore, LNC_005556, an antisense DE lncRNA, was negatively correlated with lupus nephritis occurrence and may regulate the upregulated IGLL5 in patients. CONCLUSIONS The current study provides insights into the dysregulation of lncRNAs and nearby mRNAs in SLE, highlighting potential key players in the pathogenesis of the disease.
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Affiliation(s)
- Tao Liu
- Department of Rheumatology and Immunology, The First Hospital of Jilin University, Changchun, 130021, China
| | - Mingyue Yang
- Department of Translational Medicine, The First Hospital of Jilin University, Changchun, 130021, China
| | - Xiunan Feng
- Department of Rheumatology and Immunology, The First Hospital of Jilin University, Changchun, 130021, China
| | - Xiaojuan Zou
- Department of Rheumatology and Immunology, The First Hospital of Jilin University, Changchun, 130021, China
| | - Ying Xia
- Department of Translational Medicine, The First Hospital of Jilin University, Changchun, 130021, China
| | - Lu Chen
- Department of Rheumatology and Immunology, The First Hospital of Jilin University, Changchun, 130021, China
| | - Zixin Gao
- Department of Rheumatology and Immunology, The First Hospital of Jilin University, Changchun, 130021, China
| | - Ling Zhao
- Department of Rheumatology and Immunology, The First Hospital of Jilin University, Changchun, 130021, China.
| | - Xiaosong Wang
- Department of Translational Medicine, The First Hospital of Jilin University, Changchun, 130021, China.
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Kume M, Din J, Zegarra-Ruiz DF. Dysregulated Intestinal Host-Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models. Microorganisms 2025; 13:556. [PMID: 40142449 PMCID: PMC11944652 DOI: 10.3390/microorganisms13030556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 02/21/2025] [Accepted: 02/27/2025] [Indexed: 03/28/2025] Open
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation that affects multiple organs, with its prevalence varying by ethnicity. Intestinal dysbiosis has been observed in both SLE patients and murine models. Additionally, intestinal barrier impairment is thought to contribute to the ability of pathobionts to evade and breach immune defenses, resulting in antigen cross-reactivity, microbial translocation, subsequent immune activation, and, ultimately, multiple organ failure. Since the detailed mechanisms underlying these processes are difficult to examine using human samples, murine models are crucial. Various SLE murine models, including genetically modified spontaneous and inducible murine models, offer insights into pathobionts and how they dysregulate systemic immune systems. Furthermore, since microbial metabolites modulate systemic immune responses, bacteria and their metabolites can be targeted for treatment. Based on human and mouse research insights, this review examines how lupus pathobionts trigger intestinal and systemic immune dysregulation. Therapeutic approaches, such as fecal microbiota transplantation and dietary adjustments, show potential as cost-effective and safe methods for preventing and treating SLE. Understanding the complex interactions between the microbiota, host factors, and immune dysregulation is essential for developing novel, personalized therapies to tackle this multifaceted disease.
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Affiliation(s)
| | | | - Daniel F. Zegarra-Ruiz
- Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA; (M.K.); (J.D.)
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18
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Hu Y, Wang P, Cao X, Wu Z, Feng Y. The effectiveness of telitacicept in patients with systemic lupus erythematosus: A retrospective, real-world study. Lupus 2025; 34:133-139. [PMID: 39715630 DOI: 10.1177/09612033241311330] [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: 12/25/2024]
Abstract
OBJECTIVE Despite some study demonstrated the effectiveness of telitacicept in patients with systemic lupus erythematosus (SLE), a noticeable gap exists in real-world data. This study aimed to examine the effectiveness and safety of telitacicept in patients with SLE in the real-world. METHOD This retrospective study enrolled patients with SLE at the Tangdu Hospital from January 2022 to January 2023. These patients were administered telitacicept at 80 mg or 160 mg dosage. The observed outcomes were changes in the SLE Responder Index 4 (SRI-4), disease activity, renal function, and immunological indicators. RESULT Sixty-one patients were enrolled, with 60 patients completed the 24-week follow-up, and 30 completed the 52-week. The SRI-4 response rates at 4, 12, 24, and 52 weeks were 52.5%, 67.2%, 75.4%, and 80.0%, respectively. No statistically differences were observed in the SRI-4 response rates between the 80 mg and 160 mg doses at any of the time points (all p > 0.05). By 52 weeks, the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index scores were significant decreased from baseline (p < 0.001), and complement 3 and 4 levels (p = 0.001), albumin levels (p = 0.004), and the overall change in glucocorticoid dosage (p < 0.001) were all significantly increased, with all showing significant changes over time (p < 0.001). During the study, 3 (4.9%) patients experienced infection, and 1 (1.6%) developed an allergy at the injection site. CONCLUSION Telitacicept exhibited a highly effective and favorable safety in patients with SLE, with improved renal and hematological manifestations and facilitated a reduction in glucocorticoid medication usage.
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Affiliation(s)
- Yinxiu Hu
- Department of Rheumatology and Immunology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| | - Pengyu Wang
- Department of Rheumatology and Immunology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| | - Xue Cao
- Department of Rheumatology and Immunology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| | - Zhenbiao Wu
- Department of Rheumatology and Immunology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China
| | - Yuan Feng
- Department of Rheumatology and Immunology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China
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Rojas-Cadena M, Rodríguez-Arcentales F, Narváez-Cajas J, Arias-Intriago M, Morales Orbe K, Izquierdo-Condoy JS. Myopericarditis and Pericardial Effusion as the Initial Presentation of Systemic Lupus Erythematosus in a Patient with Sickle Cell Trait: A Case Report. J Clin Med 2025; 14:920. [PMID: 39941591 PMCID: PMC11818129 DOI: 10.3390/jcm14030920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 01/23/2025] [Accepted: 01/27/2025] [Indexed: 02/16/2025] Open
Abstract
Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with rare but severe cardiac manifestations, including myocarditis and pericarditis. The coexistence of SLE with sickle cell trait (SCT), an inherited hemoglobinopathy prevalent among individuals of African descent, is exceptionally rare and presents significant diagnostic challenges due to overlapping clinical features. Objective: To describe the case of an Afro-Ecuadorian male with SLE and sickle cell trait who developed an uncommon presentation of myopericarditis and pericardial effusion. Case report: A 48-year-old African American male with no prior medical history presented with persistent fever, polyarticular arthralgias, and pleuritic chest pain. Investigations revealed sickle cell trait (SCT) and myopericarditis with pericardial effusion, marking the initial manifestation of SLE. Diagnostic delays occurred due to overlapping symptoms and a family history of sickle cell disease. Laboratory findings showed elevated hemoglobin S (<50%), positive ANA (1:1280, coarse speckled pattern), and anti-Smith/RNP antibodies, meeting EULAR/ACR 2019 criteria for SLE. Cardiac MRI confirmed myopericarditis. Treatment with pulse methylprednisolone, oral prednisone, and mycophenolate mofetil resulted in clinical improvement, with stable disease control on immunomodulatory therapy during follow-up. Conclusions: This case highlights the diagnostic complexity of SLE in patients with SCT, particularly when presenting with myopericarditis as the initial manifestation. It emphasizes the importance of a comprehensive diagnostic approach and timely initiation of immunosuppressive therapy to optimize clinical outcomes. This report broadens the understanding of overlapping syndromes involving SLE and SCT.
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Affiliation(s)
- Marlon Rojas-Cadena
- Medical Science Faculty, Universidad Católica del Ecuador, Quito 170525, Ecuador
| | | | - Jose Narváez-Cajas
- Medical Science Faculty, Universidad Católica del Ecuador, Quito 170525, Ecuador
| | - Marlon Arias-Intriago
- Department Section of Histology, Faculty of Medical Science, Universidad Central del Ecuador, Quito 170402, Ecuador
| | - Karen Morales Orbe
- One Health Research Group, Universidad de las Américas, Quito 170521, Ecuador
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20
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Jafari AJ, McGee C, Klimas N, Hebert AA. Monoclonal antibodies for the management of cutaneous lupus erythematosus: an update on the current treatment landscape. Clin Exp Dermatol 2025; 50:314-322. [PMID: 39243383 DOI: 10.1093/ced/llae374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 08/07/2024] [Accepted: 08/27/2024] [Indexed: 09/09/2024]
Abstract
Cutaneous lupus erythematosus (CLE) is a complex autoimmune disease often characterized by a multitude of skin findings. CLE is generally classified into three main categories: acute CLE, subacute CLE and chronic CLE. The current therapeutic guidelines for CLE include counselling patients on general measures and medication regimens. Treatment options include optimized photoprotection, avoidance of environmental triggers, corticosteroids, topical and systemic immunomodulators, and antimalarials. To date, no biologic medications (i.e. monoclonal antibodies, mAbs) are approved for CLE. The first mAb for the treatment of both systemic lupus erythematosus (SLE) and active lupus nephritis was belimumab, and was approved for these diseases in 2011 and 2020, respectively. Belimumab is a specific inhibitor of B-lymphocyte stimulator. Anifrolumab, a type I interferon receptor antagonist, was approved in 2021 for SLE. Other mAbs with different targets, including a novel biologic that inhibits blood dendritic cell antigen 2, are currently under investigation for CLE. This review will describe the general treatment landscape for CLE. Selected studies related to these various mAbs will be discussed, as well as their safety profiles and efficacies demonstrated in clinical trials. Biologic medications can potentially augment the number of treatment options for patients living with CLE.
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Affiliation(s)
- Alexander J Jafari
- Department of Dermatology, UTHealth McGovern Medical School, Houston, TX, USA
| | | | - Natasha Klimas
- Department of Dermatology, UTHealth McGovern Medical School, Houston, TX, USA
| | - Adelaide A Hebert
- Department of Dermatology, UTHealth McGovern Medical School, Houston, TX, USA
- Department of Pediatrics, UTHealth McGovern Medical School, Houston, TX, USA
- Department of Dermatology, MD Anderson Cancer Center, Houston, TX, USA
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21
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Zeng L, Yang L, Zhang Y, Lan T, An Y, He P, Wen X, Deng S, Zhang Z, Liu J, Zhou Q. Unravelling the TCRβ repertoire: a key to unlocking the immunopathogenesis and precision medicine in SLE. Lupus Sci Med 2025; 12:e001384. [PMID: 39832907 PMCID: PMC11751993 DOI: 10.1136/lupus-2024-001384] [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: 09/07/2024] [Accepted: 01/01/2025] [Indexed: 01/22/2025]
Abstract
OBJECTIVES SLE is a multifaceted autoimmune disorder with a complex pathogenesis involving genetic, environmental and hormonal factors, which converge on immune dysregulation. The T cell receptor (TCR) repertoire's role in SLE has garnered significant interest due to its potential in both diagnostics and therapeutics. Our study aimed to delineate the variances in the TCRβ repertoire between patients with SLE and healthy individuals, correlating these differences with the severity and subtypes of SLE. METHODS We conducted an analysis of blood samples from 50 treatment-naive patients with SLE and 50 healthy donors, employing RNA extraction, high-throughput sequencing and subsequent bioinformatics analysis. RESULTS Our findings revealed significant alterations in TRBV and TRBJ gene usage frequencies, indicative of a skewed TCR repertoire in patients with SLE. Notably, nine hub TRBV genes were identified as potential biomarkers for SLE with high diagnostic accuracy. Furthermore, we observed a reduction in TCR diversity, characterised by a lower diversity 50 value and increased clonal expansion, which correlated with disease severity. CONCLUSIONS The TCRβ repertoire is significantly altered in SLE, with potential implications for diagnostics and therapeutics. The identified hub genes may serve as novel biomarkers for SLE, and the findings contribute to the understanding of the immunopathogenesis of the disease.
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Affiliation(s)
- Li Zeng
- Department of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Lijing Yang
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yichen Zhang
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Tianzuo Lan
- Department of Rheumatology, The First People's Hospital of Guiyang, Guiyang, Guizhou Province, China
| | - Yang An
- Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, China
| | - Pengming He
- Department of Technology, Chengdu ExAb Biotechnology, Ltd, Chengdu, China
| | - Xueping Wen
- Department of Technology, Chengdu ExAb Biotechnology, Ltd, Chengdu, China
| | - Shaoping Deng
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Zhixin Zhang
- Department of Technology, Chengdu ExAb Biotechnology, Ltd, Chengdu, China
| | - Jian Liu
- Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Qiao Zhou
- Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Qionglai Medical Center Hospital, Qionglai, Sichuan, China
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Xu Y, Wang Z, Jia T, Liang S. Exploring potential drug targets for SLE through Mendelian randomization and network pharmacology. PLoS One 2025; 20:e0316481. [PMID: 39823480 PMCID: PMC11741580 DOI: 10.1371/journal.pone.0316481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 12/11/2024] [Indexed: 01/19/2025] Open
Abstract
BACKGROUND Systemic lupus erythematosus (SLE) is a complex and incurable autoimmune disease, so several drug remission for SLE symptoms have been developed and used at present. However, treatment varies by patient and disease activity, and existing medications for SLE were far from satisfactory. Novel drug targets to be found for SLE therapy are still needed. METHODS Mendelian randomization (MR), an observational study way, was performed to explore potential drug targets for SLE using protein quantitative trait loci (pQTL) from recently published genome-wide association studies (GWAS) of cerebrospinal fluid (CSF) and plasma proteins, which obtained genetic instruments for 154 CSF proteins of 971 participants, and 734 plasma proteins of 23591 participants. Bidirectional Mendelian randomization analysis, colocalization analysis, and phenotype scanning were performed to find key proteins for SLE. In addition, external data verification was implemented to further consolidate the Mendelian randomization findings. Candidate proteins as targets to find drugs and discuss the druggability. Finally, Network pharmacology and molecular docking methods were used to verify the effects of Voclosporin and Cyclosporine on SLE targets. Protein-protein interaction (PPI) and core target analysis of candidate drugs and SLE overlapping targets were performed to identify potential hub targets and interactions. The affinity between drug targets and SLE targets was confirmed by molecular docking. RESULTS In the preliminary analysis, we identified four key proteins as possible drug targets in CSF and plasma proteins, included ICAM-1(P = 4.62E-05, OR = 0.90(0.86, 0.95)), sICAM-1(P = 4.62E-05, OR = 0.49(0.35, 0.69)), FCG2B (P = 7.63E-11, OR = 0.57(0.48, 0.67)), PPP3CA; PPP3R1 (P = 5.47E-07, OR = 0.66(0.57, 0.78)). Among them, ICAM1 was detected in both CSF and plasma proteins. By excluding reverse causality, confounding factors, and linkage disequilibrium (LD), we identified PPP3CA; PPP3R1 as novel drug targets for SLE, including Voclosporin and Cyclosporine. Finally, the Drugbank database shows that novel drugs contain 33 targets for treating SLE. PPI suggested that SIRT1, ACE, PTGS2, and BACE1 were pivotal targets for SLE treatment. In addition, the molecular docking showed that the bioactive molecules of Voclosporin and Cyclosporine had a good affinity with the target of SLE. CONCLUSIONS Our integrative analysis suggested that levels of circulating PPP3CA; PPP3R1 had causal effects on SLE risk and served as potential treatment targets. Moreover, this study provides new evidence for Voclosporin as an SLE treatment through Mendelian randomization and Network pharmacology, and warrants further clinical investigation.
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Affiliation(s)
- Yanan Xu
- Department of Laboratory, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China
| | - Zelin Wang
- Department of Laboratory, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China
| | - Tiewen Jia
- Department of Laboratory, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China
| | - Shufen Liang
- Department of Laboratory, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China
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23
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Wang Q, Zhao X, Wang S, Lu S. Sarcopenia and immune-mediated inflammatory diseases: Evaluating causality and exploring therapeutic targets for sarcopenia through Mendelian randomization. Int Immunopharmacol 2025; 144:113687. [PMID: 39591827 DOI: 10.1016/j.intimp.2024.113687] [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: 05/30/2024] [Revised: 10/03/2024] [Accepted: 11/18/2024] [Indexed: 11/28/2024]
Abstract
BACKGROUND An increasing body of evidence has revealed the association between immune-mediated inflammatory diseases (IMIDs) and sarcopenia. However, a genetically direct causality between IMIDs and sarcopenia remains elusive. METHODS To investigate the relationship between IMIDs and sarcopenia-related traits and identify potential therapeutic targets, a Mendelian randomization (MR) was performed. We collected publicly available genome-wide association studies (GWAS) data for seven common IMIDs, including systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PSO), ankylosing spondylitis (AS), and rheumatoid arthritis (RA). Additionally, summary-level GWAS data for sarcopenia-related traits, including appendicular lean mass (ALM), left-hand grip strength, and right-hand grip strength were collected. To search for therapeutic targets, we used two types of genetic instruments to proxy the exposure of druggable genes, including genetic variants within or nearby drug targets and expression quantitative trait loci (eQTLs) of drug targets. Two-sample MR and summary-data-based MR (SMR) were used to calculate effect estimates, and sensitivity analyses were implemented for robustness. Drug tractability, gene enrichment analysis, and protein-protein interaction (PPI) analysis were used to validate the biological and clinical significance of the selected drug targets. RESULTS The two-sample MR analysis indicated the existence of casual associations between IMIDs and sarcopenia-related traits in the overall and sex-stratified populations. In particular, PSO had causal effects on decreased ALM, which showed significance in all six MR analysis tests with directional consistency in the overall population. Grounded in this robust association, HLA-DRB5, HLA-DRB1, and AGER were identified as potential therapeutic targets for ALM decline by drug target MR and further confirmed by SMR analysis. These genes were associated with therapeutic agents currently undergoing evaluations in clinical trials. Gene enrichment and PPI analysis indicated a strong association of these genes with immune functions. CONCLUSIONS This MR study contributes novel genetic evidence supporting the causal link between IMIDs and sarcopenia, with a particular emphasis on the association between PSO and decreased ALM. Additionally, AGER, HLA-DRB1, and HLA-DRB5 emerge as potential therapeutic targets for ALM decline.
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Affiliation(s)
- Qijun Wang
- Department of Orthopedics & Elderly Spinal Surgery, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China
| | - Xuan Zhao
- Department of Orthopedics & Elderly Spinal Surgery, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China
| | - Shuaikang Wang
- Department of Orthopedics & Elderly Spinal Surgery, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China
| | - Shibao Lu
- Department of Orthopedics & Elderly Spinal Surgery, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China.
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Zhang L, Yu L, Li Q, Ni M, Dong Q, Bao Y, Zhang J, Ruan D, Meng Z, Lai N. TLR10 expression in unswitched memory B associates with the disease activity of patients with systemic lupus erythematosus. Clin Rheumatol 2025; 44:217-227. [PMID: 39537946 DOI: 10.1007/s10067-024-07231-9] [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: 08/14/2024] [Revised: 10/30/2024] [Accepted: 11/08/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVE Systemic lupus erythematosus (SLE) is characterized by impaired B-cell function and a distinct B-cell phenotype. Toll-like receptor (TLR) 10 is highly expressed in human B cells and can regulate B-cell activation. Here, we examined the variations in TLR10 expression across B-cell subpopulations and its impact on the disease activity in SLE patients. METHODS Thirty-one patients with stable SLE, 30 patients with active SLE, and 28 healthy controls (HCs) were recruited. Flow cytometry was performed to assess the prevalence of B-cell subpopulations and their TLR10 expression. The diagnostic value of unswitched memory B cells (UMB) and double-negative B cells (DNB) in relation to disease activity was determined. The correlations between TLR10 expressions in B-cell subpopulations and disease activity were further evaluated, respectively. RESULTS Compared with the HCs, the stable patients exhibited significantly reduced Naive B proportion and elevated switched memory B and DNB proportion, while active patients presented markedly decreased UMB and increased DNB proportion. Furthermore, the receiver operating characteristics analysis revealed that UMB was more reliable than DNB in diagnosing SLE disease activity. Among the B-cell subsets, only the TLR10 expression in UMB was notably diminished in SLE patients, particularly in active patients. Importantly, TLR10 expression in UMB was negatively correlated with the disease activity. CONCLUSION UMB could serve as a promising biomarker for SLE disease activity, and the TLR10 expression in UMB was negatively correlated with the activity of SLE patients, suggesting that TLR10 might be involved in the disease progression of SLE by regulating the UMB function. Key Points • Active SLE patients exhibited reduced unswitched memory B cells and increased double-negative B cell proportions in blood. • Unswitched memory B cells are better predictors of disease activity in SLE than double-negative B cells. • TLR10 expression in unswitched memory B cells is markedly diminished in SLE patients. • TLR10 expression in unswitched memory B cells is negatively associated with SLE disease activity.
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Affiliation(s)
- Lumin Zhang
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Minhang Hospital, Fudan University, Shanghai, 201199, China
| | - Linchang Yu
- Department of Intensive Care Unit, Shenzhen University General Hospital, Shenzhen, 518071, China
| | - Quanfu Li
- Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, The Ministry of Education, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Meiping Ni
- Department of Scientific Research, Minghang Hospital, Fudan University, Shanghai, 201199, China
| | - Qiongzhu Dong
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Minhang Hospital, Fudan University, Shanghai, 201199, China
| | - Yufang Bao
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Minhang Hospital, Fudan University, Shanghai, 201199, China
| | - Jinguan Zhang
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Minhang Hospital, Fudan University, Shanghai, 201199, China
| | - Danping Ruan
- Department of Stomatology, Minhang Hospital, Fudan University, Shanghai, 201199, China.
| | - Zhefeng Meng
- Department of Scientific Research, Minghang Hospital, Fudan University, Shanghai, 201199, China.
| | - Nannan Lai
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Minhang Hospital, Fudan University, Shanghai, 201199, China.
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Masurkar PP, Reckleff J, Princic N, Limone B, Schwartz H, Karis E, Zollars E, Costenbader K. Real-world treatment patterns, healthcare resource utilisation and costs in patients with SLE in the USA. Lupus Sci Med 2024; 11:e001290. [PMID: 39719312 PMCID: PMC11683911 DOI: 10.1136/lupus-2024-001290] [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: 06/20/2024] [Accepted: 11/30/2024] [Indexed: 12/26/2024]
Abstract
OBJECTIVE To evaluate the treatment patterns, medication adherence, concomitant corticosteroid use, factors influencing sequence of therapies (SOTs), healthcare resource utilisation (HCRU) and associated costs in adults with SLE in the USA. METHODS Claims data from the Merative MarketScan Commercial and Medicare Supplemental Database between 2011 and 2019 were used to identify patients with incident SLE. The date of first claim with SLE was defined as the index date, with a 24-month pre-index and ≥24-month post-index period. Descriptive statistics were used to evaluate patient demographics and baseline clinical characteristics, treatment patterns, adherence, HCRU and cost. Multivariable-adjusted logistic regression models were used to identify factors associated with transition between SOTs. RESULTS Overall, 2476 patients received SLE treatment. The mean (SD) age was 46.9 (14.1) years and the mean (SD) follow-up duration was 47.8 (15.7) months. High corticosteroid use was prevalent in all SOTs (≥1 corticosteroid; average dose, 16.8-19.3 mg/day; 50%-60% patients). Antimalarials were most commonly prescribed in SOT 1 (85.7%), and immunosuppressants in SOT 2 and 3 (85.4% and 77.5%, respectively). Transition frequency from SOT 1-2 (38.4%) and SOT 2-3 (16.9%) was influenced by immunosuppressant prescription, concomitant corticosteroid use, sex, severe disease activity, non-persistence and age. Adherence was highest for biologics, followed by antimalarials and immunosuppressants. SLE-related HCRU and associated costs increased with SOT progression (mean (SD) at baseline vs SOT 3, US$19 489 (US$45 336) vs US$23 201 (US$39 628)). CONCLUSION SLE treatment regimens with greater adherence and reduced corticosteroid use, HCRU and associated costs are needed.
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Affiliation(s)
| | | | - Nicole Princic
- Merative (Formerly IBM Watson Health), Bethesda, Maryland, USA
| | - Brendan Limone
- Merative (Formerly IBM Watson Health), Bethesda, Maryland, USA
| | - Hana Schwartz
- Merative (Formerly IBM Watson Health), Bethesda, Maryland, USA
| | | | | | - Karen Costenbader
- Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
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Tatar Z, Basakci Calik B, Gur Kabul E, Dundar Ok Z, Cobankara V. Investigation of lower extremity performance, balance, and fatigue in individuals with systemic lupus erythematosus: A comparative study. Clin Biomech (Bristol, Avon) 2024; 120:106372. [PMID: 39531864 DOI: 10.1016/j.clinbiomech.2024.106372] [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: 07/01/2024] [Revised: 10/22/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND The aim of this study was to investigate lower extremity performance, balance, fatigue and pain in individuals with Systemic Lupus Erythematosus and compare them with healthy controls. METHODS 41 participants (Systemic Lupus Erythematosus n = 21 and mean age = 38.33 ± 13.37; healthy group n = 20 and mean age = 38.95 ± 12.62 years) were included in the study. Lower extremity performance was evaluated with timed up and go test and 30 s sit-to-stand test, static and dynamic balance with Sensamove Miniboard, fatigue levels with Visual Analog Scale and Fatigue Severity Scale and pain intensity with Visual Analog Scale. FINDINGS Significant differences were found in favor of the healthy group in the sit-to-stand test (p = 0.001), timed up and go test (p = 0.001), static balance-center (p = 0.020), front (p = 0.001), back (p = 0.002), left (p = 0.001), right (p = 0.001); proprioception-left (p = 0.004), reaction time-front (p = 0.002) and left (p = 0.016); travel time-front (p = 0.001), back (p = 0.001), left (p = 0.001) and right (p = 0.001), Fatigue Severity Scale (p = 0.001); Visual Analog Scale-fatigue (p = 0.001) and Visual Analog Scale-pain (p = 0.001). In Systemic Lupus Erythematosus, timed up and go test had low correlation with travel time-back (r = -0.449; p = 0.041). Visual Analog Scale-fatigue had low correlation with proprioception-left (r = 0.484; p = 0.026) and proprioception-right (r = 0.461; p = 0.035). Visual Analog Scale-pain had moderate correlation with proprioception-back (r = 0.521; p = 0.015) and low correlation with proprioception-right (r = 0.441; p = 0.045). INTERPRETATION Compared to healthy, individuals with Systemic Lupus Erythematosus had worse lower extremity performance, static/dynamic balance, fatigue, and pain. Dynamic balance-back was related to lower extremity performance. Fatigue was related to left-right proprioception, and pain was related to back-right proprioception.
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Affiliation(s)
- Zulal Tatar
- Faculty of Physiotherapy and Rehabilitation, Pamukkale University, Denizli, Turkey
| | - Bilge Basakci Calik
- Faculty of Physiotherapy and Rehabilitation, Pamukkale University, Denizli, Turkey.
| | - Elif Gur Kabul
- Faculty of Health Sciences, Physiotherapy and Rehabilitation, Uşak University, Uşak, Turkey.
| | - Zeynep Dundar Ok
- Department of Rheumatology, Medical Faculty, Pamukkale University, Denizli, Turkey.
| | - Veli Cobankara
- Department of Rheumatology, Medical Faculty, Pamukkale University, Denizli, Turkey.
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Li XZ, Li YW, Huang CY, Liu JL, Liu RB, Zhang ZX, Yan JZ, Zhang C. Humoral immunity and safety of respiratory virus vaccines in systemic lupus erythematosus population: a meta-analysis based on twenty-five observational studies. Ann Med 2024; 56:2392882. [PMID: 39155852 PMCID: PMC11334742 DOI: 10.1080/07853890.2024.2392882] [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: 12/13/2023] [Revised: 03/07/2024] [Accepted: 03/29/2024] [Indexed: 08/20/2024] Open
Abstract
BACKGROUND Systemic lupus erythematosus (SLE), an extensive autoimmune disorder, compromises viral resistance and alters immune responses post respiratory virus vaccines. This study aims to assess immune response levels and safety in SLE patients following respiratory virus vaccines. METHODS Extensive searches, until 1 March 2024, were conducted using PubMed, EMBASE, and Cochrane Library. Outcomes, encompassing seroconversion rate (SCR), antibody and IgG titers, neutralizing antibodies, anti-spike antibodies, anti-receptor binding domain (RBD) IgG, and adverse events, were appraised. RESULTS Sixteen articles, comprising 25 observational studies, were included. SLE patients exhibited lower SCR (OR = 0.42, 95%CI: 0.26 to 0.69), antibody titers (SMD=-2.84, 95%CI: -3.36 to -1.61), and neutralizing antibodies (OR = 0.27, 95%CI: 0.13 to 0.56) compared to the healthy population post respiratory virus vaccines. Notably, differences were statistically insignificant for anti-RBD IgG (OR = 1.75, 95%CI: 0.10 to 29.42), IgG titers (SMD=-2.54, 95%CI: -5.57 to -0.49), anti-spike antibodies (OR = 0.35, 95%CI: 0.08 to 1.53), injection site discomfort (OR = 1.03, 95%CI: 0.52 to 2.06), fatigue (OR = 1.23, 95%CI: 0.74 to 2.03), fever (OR = 1.02, 95%CI: 0.64 to 1.63), localized reactions (OR = 0.69, 95%CI: 0.37 to 1.30), systemic reactions (OR = 1.00, 95%CI: 0.59 to 1.69), allergic reactions (OR = 5.11, 95%CI: 0.24 to 107.10), self-reported vaccination-related adverse events (OR = 1.61, 95%CI: 0.56 to 4.63), and disease flares after vaccination (OR = 1.00, 95%CI: 0.14 to 7.28). CONCLUSION Despite the reduced immune response and host protection in SLE patients post-Corona Virus Disease 2019 (COVID-19) and influenza vaccines compared to the healthy population, safety profiles are comparable. Therefore, it is recommended that SLE patients receive COVID-19 and influenza viral vaccines to fortify their resistance.
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Affiliation(s)
- Xiao-Zheng Li
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Ya-Wei Li
- Department of Medical, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Cheng-Yang Huang
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Jia-Ling Liu
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Run-Ben Liu
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Zhi-Xin Zhang
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Jin-Zhu Yan
- Department of Gynaecology and Obstetrics, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Chao Zhang
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China
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Yang G, Li M, Zhang Y, Li X, Xin T, Hao J. Mechanisms of Rehmannioside A Against Systemic Lupus Erythematosus Based on Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation. Cell Biochem Biophys 2024; 82:3489-3498. [PMID: 39033091 DOI: 10.1007/s12013-024-01435-1] [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: 07/11/2024] [Indexed: 07/23/2024]
Abstract
The effect of rehmannioside A (ReA) on systemic lupus erythematosus (SLE) is not clear and needs further study. In this study, SLE-related targets were obtained from the DisGeNet and GeneCards databases, while ReA-related targets were obtained from the SwissTarget and SuperPred databases. A protein-protein interaction network of intersected targets was constructed using the STRING platform. After selecting the intersected targets, GO and KEGG enrichment analyses were performed via the R package "clusterProfiler". The relationships between ReA and various core targets were assessed via molecular docking, and molecular dynamics simulation was conducted for optimal core protein-compound complexes obtained by molecular docking. The top five targets in the ranking of degree value were HSP90AA1, HIF1A, PIK3CA, MTOR, and TLR4. Significant biological processes mainly included response to oxidative stress and response to reactive oxygen species. The potential pathways of ReA in the treatment of SLE mainly focused on the PI3K-Akt signaling pathway, neutrophil extracellular trap formation, and Apoptosis. Molecular docking showed that ReA had the highest binding affinity for mTOR, suggesting that mTOR is a key target of ReA against SLE. Molecular dynamics simulations revealed good binding abilities between ReA and mTOR. In conclusion, ReA exerts its effects on SLE through multiple targets and pathways, with mTOR being a key target of ReA against SLE.
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Affiliation(s)
- Guofei Yang
- Department of Dermatology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medica1 University, Guangzhou, China
| | - Mingfang Li
- Department of Dermatology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medica1 University, Guangzhou, China
| | - Ying Zhang
- Department of Dermatology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medica1 University, Guangzhou, China
| | - Xiaohui Li
- Department of Dermatology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medica1 University, Guangzhou, China
| | - Tiantian Xin
- Department of Dermatology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medica1 University, Guangzhou, China
| | - Jin Hao
- Department of Dermatology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medica1 University, Guangzhou, China.
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Mutalipova G, Bekaryssova D, Yessirkepov M, Bekarissova S. Trends and gender disparities in the incidence of rheumatic diseases: a regional study from 2018 to 2021. Rheumatol Int 2024; 44:2847-2851. [PMID: 39307906 DOI: 10.1007/s00296-024-05725-y] [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: 08/29/2024] [Accepted: 09/14/2024] [Indexed: 01/18/2025]
Abstract
Rheumatic diseases encompass a range of entities affecting the musculoskeletal system and connective tissue due to immune dysregulation. These entities include rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis that present significant medical and social challenges by impacting individuals' quality of life and working capacity. In developing countries, where healthcare access is limited, the burden of these diseases is particularly severe. Analyzing the regional epidemiological characteristics of rheumatic diseases may enhance our understanding of risk factors and aid in developing targeted preventive measures. This study utilized data from the Republican Centre for Health Development in Kazakhstan from 2018 to 2021. The incidence of various rheumatic diseases was examined in the adult population of Shymkent, Kazakhstan, including rheumatoid arthritis, gout, osteoarthritis, systemic lupus erythematosus, dermatomyositis, scleroderma, and ankylosing spondylitis. Shymkent's total number of rheumatic disease cases rose from 52,617 in 2018 to 52,781 in 2021. Primary morbidity increased from 18,381 to 21,677 cases. Incidence rates for systemic lupus erythematosus, systemic scleroderma, and ankylosing spondylitis increased, while cases of rheumatoid arthritis and osteoarthritis showed fluctuation. Gender distribution analysis revealed that women were more frequently affected by rheumatoid arthritis and systemic lupus erythematosus whereas men were more prone to ankylosing spondylitis. The results underscore the need to tailor diagnostic and treatment approaches to account for age-and gender-specific differences in rheumatic diseases. The increased incidence of some diseases calls for new prevention and treatment strategies. This study highlights the significant burden of rheumatic diseases in Shymkent, Kazakhstan and emphasizes the importance of local epidemiological research in adapting medical practices to regional specifics.
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Affiliation(s)
- Gulmira Mutalipova
- Department of Biology and Biochemistry, South Kazakhstan Medical Academy, Shymkent, Kazakhstan
| | - Dana Bekaryssova
- Department of Biology and Biochemistry, South Kazakhstan Medical Academy, Shymkent, Kazakhstan.
| | - Marlen Yessirkepov
- Department of Biology and Biochemistry, South Kazakhstan Medical Academy, Shymkent, Kazakhstan
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Guillet S, Lazarov T, Jordan N, Boisson B, Tello M, Craddock B, Zhou T, Nishi C, Bareja R, Yang H, Rieux-Laucat F, Fregel Lorenzo RI, Dyall SD, Isenberg D, D'Cruz D, Lachmann N, Elemento O, Viale A, Socci ND, Abel L, Nagata S, Huse M, Miller WT, Casanova JL, Geissmann F. ACK1 and BRK non-receptor tyrosine kinase deficiencies are associated with familial systemic lupus and involved in efferocytosis. eLife 2024; 13:RP96085. [PMID: 39570652 PMCID: PMC11581429 DOI: 10.7554/elife.96085] [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] [Indexed: 11/22/2024] Open
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease, the pathophysiology and genetic basis of which are incompletely understood. Using a forward genetic screen in multiplex families with SLE, we identified an association between SLE and compound heterozygous deleterious variants in the non-receptor tyrosine kinases (NRTKs) ACK1 and BRK. Experimental blockade of ACK1 or BRK increased circulating autoantibodies in vivo in mice and exacerbated glomerular IgG deposits in an SLE mouse model. Mechanistically, NRTKs regulate activation, migration, and proliferation of immune cells. We found that the patients' ACK1 and BRK variants impair efferocytosis, the MERTK-mediated anti-inflammatory response to apoptotic cells, in human induced pluripotent stem cell (hiPSC)-derived macrophages, which may contribute to SLE pathogenesis. Overall, our data suggest that ACK1 and BRK deficiencies are associated with human SLE and impair efferocytosis in macrophages.
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Affiliation(s)
- Stephanie Guillet
- Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer CenterNew YorkUnited States
- Ecole doctorale Bio Sorbonne Paris Cité, Université Paris Descartes-Sorbonne Paris CitéParisFrance
| | - Tomi Lazarov
- Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer CenterNew YorkUnited States
- Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical SciencesNew YorkUnited States
| | - Natasha Jordan
- Centre for Molecular and Cellular Biology of Inflammation (CMCBI), King’s College London and Louise Coote Lupus Unit, Guy’s and Thomas’ HospitalsLondonUnited Kingdom
| | - Bertrand Boisson
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller UniversityNew YorkUnited States
- University of Paris Cité, Imagine InstituteParisFrance
| | - Maria Tello
- Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer CenterNew YorkUnited States
| | - Barbara Craddock
- SKI Stem Cell Research Core, Memorial Sloan Kettering Cancer CenterNew YorkUnited States
| | - Ting Zhou
- SKI Stem Cell Research Core, Memorial Sloan Kettering Cancer CenterNew YorkUnited States
| | - Chihiro Nishi
- Laboratory of Biochemistry & Immunology, World Premier International Immunology Frontier Research Center, Osaka UniversityOsakaJapan
| | - Rohan Bareja
- Cary and Israel Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Meyer Cancer Center Weill Cornell Medical CollegeNew YorkUnited States
| | - Hairu Yang
- Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer CenterNew YorkUnited States
| | | | | | - Sabrina D Dyall
- Department of Biosciences and Ocean Studies, Faculty of Science, University of MauritiusReduitMauritius
| | - David Isenberg
- Bioinformatics Core, Memorial Sloan Kettering Cancer CenterNew YorkUnited States
| | - David D'Cruz
- Centre for Molecular and Cellular Biology of Inflammation (CMCBI), King’s College London and Louise Coote Lupus Unit, Guy’s and Thomas’ HospitalsLondonUnited Kingdom
| | - Nico Lachmann
- Centre for Rheumatology, Division of Medicine, University College London, The Rayne BuildingLondonUnited Kingdom
| | - Olivier Elemento
- Cary and Israel Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Meyer Cancer Center Weill Cornell Medical CollegeNew YorkUnited States
| | - Agnes Viale
- Institute of Experimental Hematology, REBIRTH Cluster of Excellence, Hannover Medical SchoolHannoverGermany
| | - Nicholas D Socci
- Institute of Experimental Hematology, REBIRTH Cluster of Excellence, Hannover Medical SchoolHannoverGermany
- Marie-Josée & Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer CenterNew YorkUnited States
| | - Laurent Abel
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller UniversityNew YorkUnited States
- University of Paris Cité, Imagine InstituteParisFrance
| | - Shigekazu Nagata
- Laboratory of Biochemistry & Immunology, World Premier International Immunology Frontier Research Center, Osaka UniversityOsakaJapan
| | - Morgan Huse
- Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer CenterNew YorkUnited States
| | - W Todd Miller
- Marie-Josée & Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer CenterNew YorkUnited States
- Department of Physiology and Biophysics, Stony Brook University School of MedicineStony BrookUnited States
| | - Jean-Laurent Casanova
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller UniversityNew YorkUnited States
- University of Paris Cité, Imagine InstituteParisFrance
- Howard Hughes Medical InstituteNew YorkUnited States
- Lab of Human Genetics of Infectious Diseases, INSERM, Necker Hospital for Sick ChildrenParisFrance
- Department of Pediatrics, Necker Hospital for Sick ChildrenParisFrance
| | - Frédéric Geissmann
- Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer CenterNew YorkUnited States
- Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical SciencesNew YorkUnited States
- Centre for Molecular and Cellular Biology of Inflammation (CMCBI), King’s College London and Louise Coote Lupus Unit, Guy’s and Thomas’ HospitalsLondonUnited Kingdom
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31
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Isojima S, Li N, Rowson S, Kandane-Rahtnayake R, Koelmeyer R, Morand EF, Hoi A. Pregnancy outcomes in Australian patients with systemic lupus erythematosus. Intern Med J 2024; 54:1876-1882. [PMID: 39258417 DOI: 10.1111/imj.16524] [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: 10/21/2023] [Accepted: 08/18/2024] [Indexed: 09/12/2024]
Abstract
BACKGROUND Systemic lupus erythematosus (SLE) affects women, with the onset of disease typically around the childbearing years. AIMS This study examines the frequency and risk factors for adverse pregnancy outcomes (APOs) in an Australian cohort, and any disease flares during pregnancy and post partum. METHODS Female patients with SLE enrolled in the Australian Lupus Registry and Biobank (ALRB) between January 2007 and June 2019 were studied. Self-reported pregnancy history, including adverse foetal or maternal outcomes, was collected at the time of enrolment and updated as appropriate. Baseline demographics, clinical parameters, medication exposure and disease activity were collected. Factors associated with APO were examined using univariate and multivariate logistic regression analyses. RESULTS Pregnancy history was available in 278 patients; 30% were nulliparous. Most pregnancies occurred before the diagnosis of SLE. Patients who had pregnancies after SLE diagnosis had an earlier age of diagnosis, and had fewer pregnancies. The APO rate was 44.3% in the overall cohort, with most presenting as prematurity with or without foetal growth restriction. Women with APO were also diagnosed with SLE at a younger age and had a higher prevalence of anti-cardiolipin antibodies and hypocomplementemia. Early age of SLE diagnosis was a significant independent risk factor for APO. No increase in disease flare was observed in those who experienced APO during the observation period of ALRB. CONCLUSION This study shows a considerable incidence of APO in patients with SLE, emphasising the need for pre-pregnancy counselling and collaboration between maternal-foetal medicine specialists and rheumatologists, especially for women diagnosed with SLE at a younger age.
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Affiliation(s)
- Sakiko Isojima
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
- Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Ning Li
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
| | - Saskia Rowson
- Department of Rheumatology, Austin Health, Melbourne, Victoria, Australia
- Department of Rheumatology, Monash Health, Melbourne, Victoria, Australia
| | - Rangi Kandane-Rahtnayake
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
| | - Rachel Koelmeyer
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
| | - Eric F Morand
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
- Department of Rheumatology, Monash Health, Melbourne, Victoria, Australia
| | - Alberta Hoi
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
- Department of Rheumatology, Monash Health, Melbourne, Victoria, Australia
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Dernie F, Corby G, Robinson A, Bezer J, Mercade-Besora N, Griffier R, Verdy G, Leis A, Ramirez-Anguita JM, Mayer MA, Brash JT, Seager S, Parry R, Jodicke A, Duarte-Salles T, Rijnbeek PR, Verhamme K, Pacurariu A, Morales D, Pinheiro L, Prieto-Alhambra D, Prats-Uribe A. Standardised and Reproducible Phenotyping Using Distributed Analytics and Tools in the Data Analysis and Real World Interrogation Network (DARWIN EU). Pharmacoepidemiol Drug Saf 2024; 33:e70042. [PMID: 39532529 DOI: 10.1002/pds.70042] [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: 01/10/2024] [Revised: 10/02/2024] [Accepted: 10/06/2024] [Indexed: 11/16/2024]
Abstract
PURPOSE The generation of representative disease phenotypes is important for ensuring the reliability of the findings of observational studies. The aim of this manuscript is to outline a reproducible framework for reliable and traceable phenotype generation based on real world data for use in the Data Analysis and Real-World Interrogation Network (DARWIN EU). We illustrate the use of this framework by generating phenotypes for two diseases: pancreatic cancer and systemic lupus erythematosus (SLE). METHODS The phenotyping process involves a 14-steps process based on a standard operating procedure co-created by the DARWIN EU Coordination Centre in collaboration with the European Medicines Agency. A number of bespoke R packages were utilised to generate and review codelists for two phenotypes based on real world data mapped to the OMOP Common Data Model. RESULTS Codelists were generated for both pancreatic cancer and SLE, and cohorts were generated in six OMOP-mapped databases. Diagnostic checks were performed, which showed these cohorts had broadly similar incidence and prevalence figures to previously published literature, despite significant inter-database variability. Co-occurrent symptoms, conditions, and medication use were in keeping with pre-specified clinical descriptions based on previous knowledge. CONCLUSIONS Our detailed phenotyping process makes use of bespoke tools and allows for comprehensive codelist generation and review, as well as large-scale exploration of the characteristics of the resulting cohorts. Wider use of structured and reproducible phenotyping methods will be important in ensuring the reliability of observational studies for regulatory purposes.
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Affiliation(s)
- Francesco Dernie
- Medical Sciences Division, University of Oxford, Oxford, UK
- Pharmaco- and Device Epidemiology, Centre for Statistics in Medicines, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - George Corby
- Medical Sciences Division, University of Oxford, Oxford, UK
- Pharmaco- and Device Epidemiology, Centre for Statistics in Medicines, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Abigail Robinson
- Medical Sciences Division, University of Oxford, Oxford, UK
- Pharmaco- and Device Epidemiology, Centre for Statistics in Medicines, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - James Bezer
- Medical Sciences Division, University of Oxford, Oxford, UK
- Pharmaco- and Device Epidemiology, Centre for Statistics in Medicines, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Nuria Mercade-Besora
- Pharmaco- and Device Epidemiology, Centre for Statistics in Medicines, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Romain Griffier
- Public Health Department, Medical Information Service, Medical Informatics and Archiving Unit (IAM), University Hospital of Bordeaux, Bordeaux, France
| | - Guillaume Verdy
- Public Health Department, Medical Information Service, Medical Informatics and Archiving Unit (IAM), University Hospital of Bordeaux, Bordeaux, France
| | - Angela Leis
- Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Research Institute, Barcelona, Spain
| | | | - Miguel A Mayer
- Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Research Institute, Barcelona, Spain
- Management and Control Department, Consorci Mar Parc de Salut de Barcelona, Barcelona, Spain
| | | | | | - Rowan Parry
- Department of Medical Informatics, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Annika Jodicke
- Pharmaco- and Device Epidemiology, Centre for Statistics in Medicines, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Talita Duarte-Salles
- Department of Medical Informatics, Erasmus University Medical Centre, Rotterdam, The Netherlands
- Fundació Institut Universitari per a la Recerca a l'Atencio Primaria de Salut Jordi Gol I Gurina (IDIAPJGol), Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Peter R Rijnbeek
- Department of Medical Informatics, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Katia Verhamme
- Department of Medical Informatics, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Alexandra Pacurariu
- Real World Evidence Workstream, European Medicines Agency, Amsterdam, The Netherlands
| | - Daniel Morales
- Real World Evidence Workstream, European Medicines Agency, Amsterdam, The Netherlands
- Division of Population Health and Genomics, University of Dundee, Dundee, UK
| | - Luis Pinheiro
- Real World Evidence Workstream, European Medicines Agency, Amsterdam, The Netherlands
| | - Daniel Prieto-Alhambra
- Pharmaco- and Device Epidemiology, Centre for Statistics in Medicines, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
- Department of Medical Informatics, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Albert Prats-Uribe
- Pharmaco- and Device Epidemiology, Centre for Statistics in Medicines, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
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Liu J, Liu Y, Xu Y, Ye J, Zhu Y, Li X. Plasma exosomes may mediate the development of lupus nephritis in patients with systemic lupus erythematosus. Lupus 2024:9612033241298047. [PMID: 39482904 DOI: 10.1177/09612033241298047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2024]
Abstract
BACKGROUND Lupus nephritis (LN) is the most serious complication of systemic lupus erythematosus (SLE), and plasma exosomes may serve as a bridge. MicroRNAs (miRNAs) are abundant in exosomes, so this study aimed to explore the role of exosome-derived miRNA in the development of LN. METHODS The publicly available data containing plasma exosomal miRNAs in SLE patients and healthy controls were researched, and differential expression and functional enrichment analysis of exosomal miRNA was conducted. Then, plasma exosomes from SLE patients were extracted, and the accuracy of differential expression and functional enrichment analysis was preliminarily verified. PKH26 dye was used to label exosomes to detect whether exosomes can enter HK2 cells. Evaluation of plasma exosomes impact on cell viability was done by utilizing CCK-8 assay. Flow cytometry was used to measure cell apoptosis. RESULTS Plasma exosomes were successfully extracted and identified. Through differential expression analysis of the pulbilic data and subsequent qPCR validation, we observed that miR-20b-5p is overexpressed in plasma exosomes of SLE patients, whereas miR-181a-2-3p is downregulated. Then functional enrichment analysis revealed that these differential miRNAs primarily regulate processes such as apoptosis, autophagy, and inflammation. Then, flow cytometry analysis conducted after co-incubation of plasma exosomes and peripheral blood mononuclear cells confirmed that exosomes can indeed regulate apoptosis. And plasma exosomes can successfully enter HK2 cells without affecting cell activity. In addition, plasma exosomes promote HK2 cell apoptosis and autophagy. Overexpression of miR-181a-2-3p could inhibit HK2 cells apoptosis and upregulate the expression of bcl2, and beclin1. At the same time, a trend towards increased apoptosis rates was observed in HK2 overexpressed miR-20b-5p, although the difference did not reach statistical significance. And miR-20b-5p can enhance the expression of caspase3 and becin1 while suppressing the expression of bcl2 and LC3β. CONCLUSION Our research indicates that the abundant presence of miR-20b-5p and the depletion of miR-181a-2-3p in plasma exosomes of SLE patients may mediate the promotion of apoptosis and autophagy in HK2 cells, thereby causing kidney damage and the development of LN.
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Affiliation(s)
- Jie Liu
- Department of Dermatology and Venereology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yuanju Liu
- Department of Dermatology and Venereology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yinde Xu
- Department of Dermatology and Venereology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Jianjun Ye
- Department of Dermatology and Venereology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yun Zhu
- Department of Dermatology and Venereology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Xiaolan Li
- Department of Dermatology and Venereology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
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Triggianese P, Senter R, Perego F, Gidaro A, Petraroli A, Arcoleo F, Brussino L, Giardino F, Rossi O, Bignardi D, Quattrocchi P, Brancaccio R, Cesoni Marcelli A, Accardo PA, Lo Sardo L, Cataudella E, Guarino MD, Firinu D, Bergamini A, Spadaro G, Zanichelli A, Cancian M. Rare connective tissue diseases in patients with C1-inhibitor deficiency hereditary angioedema: first evidence on prevalence and distribution from a large Italian cohort study. Front Immunol 2024; 15:1461407. [PMID: 39493762 PMCID: PMC11527674 DOI: 10.3389/fimmu.2024.1461407] [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: 07/08/2024] [Accepted: 09/30/2024] [Indexed: 11/05/2024] Open
Abstract
Introduction In patients with Hereditary Angioedema (HAE) related to primary C1 inhibitor deficiency (C1INH), the defective clearance of immune complexes and apoptotic materials along with impairment of normal humoral response potentially leads to autoimmunity. Few studies report evidence on autoimmune diseases in C1INH-HAE, but no large population studies focus on rare connective tissue diseases (RCTDs). We aim at evaluating for the first time prevalence and distribution of RCTDs - Systemic Lupus Erytematosus (SLE), primary Sjogren Syndrome (SjS), primary antiphospholipid syndrome (APS), Systemic Sclerosis (SSc), and mixed connective tissue diseases (MCTD) in a large Italian cohort of C1INH-HAE patients. Methods A multicenter observational study includes C1INH-HAE patients from ITACA Centers throughout Italy (time frame Sept 2023-March 2024). Inclusion criteria are i. a defined diagnosis of type I or type II C1INH-HAE; ii. age ≥15 years (puberty already occurred); iii. enrollment in the ITACA Registry. The diagnosis of SLE, primary SjS, primary APS, SSc, and MCTD are made in accordance with international classification criteria. Results Data are collected from a total of 855 C1INH-HAE patients referring to 15 ITACA Centers. Patients with concomitant RCTDs were 18/855 (2.1%) with F:M ratio 3.5 and a prevalent type I C1INH-HAE diagnosis (87.2%). A diagnosis of SLE results in 44.5% of cases (n=8) while the remaining diagnoses are primary SjS (22.2%, n=4), primary APS (16.6%, n=3), SSc (11.2%, n=2), and a single case of MCTD (5.5%). The female gender is prevalent in all the RCTDs. Patients on long term prophylaxis (LTP) are significantly prevalent in RCTDs group than in the whole C1INH-HAE population (p<0.01). Conclusions A relevant prevalence of RCTDs is documented in C1INH-HAE patients, mainly SLE. Patients with RCTDs are on LTP in a significant proportion supporting the idea of a bidirectional link between C1INH-HAE and autoimmunity.
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Affiliation(s)
- P. Triggianese
- University of Rome Tor Vergata, “Fondazione PTV Policlinico Tor Vergata”, Rome, Italy
| | - R. Senter
- Department of Medicine, Azienda Ospedale-Università di Padova, Padova, Italy
| | - F. Perego
- IRCCS Istituti Clinici Scientifici Maugeri, Milano, Italy
| | - A. Gidaro
- Internal Medicine, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, ASST Fatebenefratelli-Sacco, University of Milan, Milan, Italy
| | - A. Petraroli
- Department of Internal Medicine, Clinical Immunology, Clinical Pathology and Infectious Disease, Azienda Ospedaliera Universitaria Federico II, Napoli, Italy
| | - F. Arcoleo
- Ospedali Riuniti Villa Sofia-Cervello, Unità Operativa Complessa di Patologia Clinica, Palermo, Italy
| | - L. Brussino
- Allergy and Clinical Immunology Unit, Department of Medical Sciences, University of Torino & Mauriziano Hospital, Torino, Italy
| | - F. Giardino
- Azienda Ospedaliero-Universitaria Policlinico “G.Rodolico-San Marco”, Catania, Italy
| | - O. Rossi
- Immunoallergology Unit, University Hospital of Careggi, Florence, Italy
| | - D. Bignardi
- Department of Medicine Integrated with the Territory, Ospedale Policlinico San Martino, IRCCS Ospedale Policlinico, Genova UO Allergologia, Genova, Italy
| | - P. Quattrocchi
- Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, Messina, Italy
| | - R. Brancaccio
- Dermatology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio nell’Emilia, Italy
| | | | - P. A. Accardo
- Ospedali Riuniti Villa Sofia-Cervello, Unità Operativa Complessa di Patologia Clinica, Palermo, Italy
| | - L. Lo Sardo
- Allergy and Clinical Immunology Unit, Department of Medical Sciences, University of Torino & Mauriziano Hospital, Torino, Italy
| | - E. Cataudella
- Immunoallergology Unit, University Hospital of Careggi, Florence, Italy
| | | | - D. Firinu
- Division of Allergy and Clinical Immunology, University of Cagliari, Cagliari, Italy
| | - A. Bergamini
- University of Rome Tor Vergata, “Fondazione PTV Policlinico Tor Vergata”, Rome, Italy
| | - G. Spadaro
- Department of Internal Medicine, Clinical Immunology, Clinical Pathology and Infectious Disease, Azienda Ospedaliera Universitaria Federico II, Napoli, Italy
| | - A. Zanichelli
- Operative Unit of Medicine, Angioedema Center, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - M. Cancian
- Department of Medicine, Azienda Ospedale-Università di Padova, Padova, Italy
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Lai B, Luo SF, Lai JH. Therapeutically targeting proinflammatory type I interferons in systemic lupus erythematosus: efficacy and insufficiency with a specific focus on lupus nephritis. Front Immunol 2024; 15:1489205. [PMID: 39478861 PMCID: PMC11521836 DOI: 10.3389/fimmu.2024.1489205] [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: 08/31/2024] [Accepted: 09/30/2024] [Indexed: 11/02/2024] Open
Abstract
Type I interferons (IFN-Is) are important players in the immunopathogenesis of systemic lupus erythematosus (SLE). Pathogenic events in patients with SLE are potent triggers of IFN-I induction, yet IFN-I may induce or initiate the immunopathogenesis leading to these events. Because blocking IFN-I is effective in some clinical manifestations of SLE patients, concerns about the efficacy of anti-IFN-I therapy in patients with lupus nephritis remain. Tissues from kidney biopsies of patients with lupus nephritis revealed infiltration of various immune cells and activation of inflammatory signals; however, their correlation with renal damage is not clear, which raises serious concerns about how critical the role of IFN-I is among the potential contributors to the pathogenesis of lupus nephritis. This review addresses several issues related to the roles of IFN-I in SLE, especially in lupus nephritis, including (1) the contribution of IFN-I to the development and immunopathogenesis of SLE; (2) evidence supporting the association of IFN-I with lupus nephritis; (3) therapies targeting IFN-I and IFN-I downstream signaling molecules in SLE and lupus nephritis; (4) findings challenging the therapeutic benefits of anti-IFN-I in lupus nephritis; and (5) a perspective associated with anti-IFN-I biologics for lupus nephritis treatment. In addition to providing clear pictures of the roles of IFN-I in SLE, especially in lupus nephritis, this review addresses the lately published observations and clinical trials on this topic.
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Affiliation(s)
- Benjamin Lai
- Department of Neurology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Shue-Fen Luo
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan
| | - Jenn-Haung Lai
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan
- Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan
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Mo S, Li Y, He J, Lin L. Progress of rituximab in the treatment of systemic lupus erythematosus and lupus nephritis. Front Med (Lausanne) 2024; 11:1472019. [PMID: 39430591 PMCID: PMC11486751 DOI: 10.3389/fmed.2024.1472019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 09/18/2024] [Indexed: 10/22/2024] Open
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with heterogeneous clinical manifestations, often leading to significant morbidity and mortality, particularly due to lupus nephritis (LN). The standard therapeutic approach involving mycophenolate mofetil, cyclophosphamide, and glucocorticoids has shown limitations due to cumulative toxicity and side effects. The introduction of biologic agents, especially rituximab (RTX), a chimeric monoclonal antibody targeting CD20+ B cells, has revolutionized the treatment landscape. This review synthesized the current understanding of B cells' role in SLE and LN and evaluates RTX's therapeutic impact. B cells contribute to disease pathogenesis through autoantibody production and immune complex formation, leading to tissue damage. RTX's mechanisms of action, including Complement-Dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and induction of apoptosis, have demonstrated efficacy in both SLE and LN treatment. Clinical studies have reported remission rates and improved renal outcomes with RTX use, although challenges such as human anti-chimeric antibody development and optimal dosing persist. The review emphasized the need for continued research to elucidate RTX's long-term benefits and risks, and to explore personalized treatment strategies that incorporate B cell biology for better disease management in SLE and LN.
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Affiliation(s)
- Shouqi Mo
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
- Department of Rheumatology, Jieyang People's Hospital, Jieyang, China
| | - Yilan Li
- Department of General Family Medicine, Jieyang People's Hospital, Jieyang, China
| | - Junbing He
- Jieyang Medical Research Center, Jieyang People's Hospital, Jieyang, China
| | - Ling Lin
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
- Department of Rheumatology, Shantou University Medical College, Shantou, China
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Wind M, Fierro JJ, Bloemenkamp KWM, de Leeuw K, Lely AT, Limper M, Sueters M, Teng YKO, Walter IJ, Kooiman J. Pregnancy outcome predictors in systemic lupus erythematosus: a systematic review and meta-analysis. THE LANCET. RHEUMATOLOGY 2024; 6:e667-e683. [PMID: 39153486 DOI: 10.1016/s2665-9913(24)00160-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 06/04/2024] [Accepted: 06/04/2024] [Indexed: 08/19/2024]
Abstract
BACKGROUND To enhance patient-tailored preconception risk assessment for women with systemic lupus erythematosus (SLE), knowledge on risk factors associated with adverse pregnancy outcomes is required. Therefore, we did a systematic review and meta-analysis to identify and provide unambiguous effect sizes of preconception predictors of pregnancy outcomes in women with SLE. METHODS In this systematic review and meta-analysis, we searched PubMed and Embase for studies reporting preconception predictors of pregnancy outcomes in women with SLE, from database inception to Aug 22, 2023. Studies were included if they presented original, quantitative data on pregnant women with SLE and reported on preconception risk factors on at least one of the outcomes as defined in the protocol. Studies were excluded if they had a sample size of less than 20 patients, were restricted to multiple pregnancies, had unclear timing of prognostication, or exclusively reported a composite outcome. Literature screening, data extraction, and risk-of-bias assessment (quality in prognostic studies tool) were done by two reviewers independently, in a blinded, standardised manner. The reported outcomes included livebirth, pre-eclampsia, small for gestational age, preterm birth, pregnancy loss before and after 20 weeks of gestation, and SLE flares. We computed pooled univariate odds ratios (ORs) and 95% CIs using a random effects model. We assessed heterogeneity using the I2 statistic and prediction intervals. This study is registered with PROSPERO, CRD42022344732. FINDINGS Of the 6705 unique articles identified, 72 (1·1%) were included in the meta-analysis, comprising 10 355 pregnancies in 8065 women with SLE. One potentially eligible study was retracted and therefore removed from our analysis. Previous lupus nephritis was associated with decreased livebirth probability (OR 0·62 [95% CI 0·47-0·81]; I2=0%), increased risk of preterm birth (2·00 [1·55-2·57]; I2=17%), and increased risk of pre-eclampsia (3·11 [2·35-4·12]; I2=0%). Chronic hypertension was associated with increased risk of disease flare (2·50 [1·74-3·58]; I2=0%), preterm birth (2·65 [1·87-3·77]; I2=0%), and pre-eclampsia (5·86 [3·41-10·06]; I2=33%). SLE disease activity at conception or preconception was associated with increased risk of preterm birth (2·91 [1·96-4·33]; I2=21%) and pre-eclampsia (2·32 [1·40-3·83]; I2=0%). Secondary antiphospholipid syndrome was associated with decreased livebirth probability (0·40 [0·27-0·58]; I2=0%), increased risk of pregnancy loss after 20 weeks of gestation (2·77 [1·44-5·31]; I2=0%), and increased risk of preterm birth (1·65 [1·29-2·11]; I2=0%). Across studies, risk-of-bias assessment suggested considerable bias in study attrition and confounding. INTERPRETATION We identified previous lupus nephritis, chronic hypertension, SLE disease activity before and at conception, and secondary antiphospholipid syndrome as predictors of adverse pregnancy outcomes in women with SLE. These findings contribute to an optimal patient-tailored risk assessment in preconception counselling. FUNDING None.
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Affiliation(s)
- Merlijn Wind
- Department of Obstetrics, Leiden, Netherlands; Leiden University Medical Centre, Leiden, Netherlands; Department of Obstetrics, Haaglanden Medical Centre, The Hague, Netherlands.
| | - Juan J Fierro
- Department of Rheumatology and Clinical Immunology, University Medical Centre Groningen, Groningen, Netherlands; Grupo Reproducción, Departamento de Microbiología y Parasitología, Universidad de Antioquia UdeA, Medellín, Colombia
| | | | - Karina de Leeuw
- Department of Rheumatology and Clinical Immunology, University Medical Centre Groningen, Groningen, Netherlands
| | - A Titia Lely
- Department of Obstetrics, Utrecht, the Netherlands
| | - Maarten Limper
- Department of Rheumatology and Clinical Immunology, Utrecht, the Netherlands
| | | | | | | | - Judith Kooiman
- Department of Obstetrics, Utrecht, the Netherlands; University Medical Centre Utrecht, Utrecht, the Netherlands; Department of Obstetrics, Erasmus Medical Center, Rotterdam, Netherlands
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Nori H, Kaur H, Singh S, Bhalla AK. Pattern of physical growth and pubertal changes in adolescent girls with Systemic Lupus Erythematosus. J Family Med Prim Care 2024; 13:4616-4622. [PMID: 39629427 PMCID: PMC11610807 DOI: 10.4103/jfmpc.jfmpc_480_24] [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: 03/23/2024] [Revised: 05/09/2024] [Accepted: 05/20/2024] [Indexed: 12/07/2024] Open
Abstract
Aims To study the pattern of physical growth and pubertal changes in adolescent girls with Systemic Lupus Erythematosus (SLE). Methods and Material Weight, height, BMI, waist and hip circumference among 50 adolescent SLE girls (aged 8-17 years) were cross-sectionally studied using standardized techniques and instruments. Breast development stage, presence or absence of pubic and axillary hair and age of attainment of menarche were also noted. Results With the advancement of age, weight and height of SLE girls increased but they were lighter and shorter compared to normal Indian peers. 18.4% of study girls were short-statured while only one participant was underweight. As per mid-parental height, 34.3% were predicted to have shorter final heights. BMI demonstrated an inconsistent trend with 12.3% and 9.2% being obese and overweight, respectively. Interestingly, 10.7% of SLE girls were at risk of metabolic syndrome (waist circumference >70th centile). About 50% of study girls had attained menarche (mean age: 13.04 ± 1.38 years). Appearance of pubic and axillary hair occurred around 1 year later than attainment of menarche. 33.80% of study subjects were in prepubertal stage of breast development and rest 66.20% were in advanced stages of breast development. SLE girls who had younger age at diagnosis and longer duration of therapy had significant delay in breast development and attainment of menarche. Conclusions SLE girls show delayed growth and pubertal attainments compared to their normal Indian and Western counterparts. The data presented will provide an understanding of the auxological dynamics and pattern of pubertal changes among adolescent girls with SLE living in north-western India.
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Affiliation(s)
- Harshita Nori
- Department of Pediatrics, Child Growth and Anthropology Unit, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Harvinder Kaur
- Department of Pediatrics, Child Growth and Anthropology Unit, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Surjit Singh
- Department of Pediatrics, Allergy and Immunology Unit, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Anil Kumar Bhalla
- Department of Pediatrics, Child Growth and Anthropology Unit, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
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Recio-Barbero M, Cabezas-Garduño J, Varona J, Ruiz-Irastorza G, Horrillo I, Meana JJ, Santos-Zorrozúa B, Segarra R. Clinical Predictors of Mood Disorders and Prevalence of Neuropsychiatric Symptoms in Patients with Systemic Lupus Erythematosus. J Clin Med 2024; 13:5423. [PMID: 39336910 PMCID: PMC11432540 DOI: 10.3390/jcm13185423] [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: 07/30/2024] [Revised: 08/27/2024] [Accepted: 09/09/2024] [Indexed: 09/30/2024] Open
Abstract
Background/Objectives: We aimed to determine the prevalence and clinical correlations of mood disorders in a sample of systemic lupus erythematosus (SLE) patients. Hence, we hypothesized that the prevalence of mood disorders would be lower than reported in the literature and that patients would remain clinically stable and show less damage accrual despite low-dose corticosteroid prescription. Methods: In total, 92 SLE outpatients gave informed consent to participate in this cross-sectional study. Psychiatric and autoimmune clinical data were obtained, and a structured psychiatric interview was performed. The main clinical scales for the assessment of clinical symptomatology were included. To examine the potential relationships of presenting a mood disorder in SLE, clinical correlations and multivariate analyses were performed. Results: Mood disorders were the most prevalent disorder reported by SLE patients (16%), followed by adjustment disorders (5%). A significant proportion of patients presented psychosocial disturbances that did not meet the ICD-10 criteria for psychiatric diagnosis. According to the cut-off criterion for the Montgomery-Åsberg Depression Rating Scale (MADRS), up to 27% of the sample met the clinical criteria for depression. The multivariate analysis revealed a relationship between the presence of a mood disorder with total scores of the MADRS and the Young Mania Rating Scale (YMRS). Conclusions: The prevalence of mood disorders in patients with SLE was lower than previously reported. Although self-report clinical scales are useful for assessing clinical symptomatology, they should not be used in place of a comprehensive standardized interview conducted by a trained mental health specialist. Multidisciplinary teamwork is required for the early identification and therapeutic management of autoimmune patients with neuropsychiatric disorders.
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Affiliation(s)
- María Recio-Barbero
- BioBizkaia Health Research Institute, 48903 Barakaldo, Spain
- University of the Basque Country, UPV/EHU, 48940 Leioa, Spain
| | - Janire Cabezas-Garduño
- BioBizkaia Health Research Institute, 48903 Barakaldo, Spain
- Department of Psychiatry, Cruces University Hospital, 48903 Barakaldo, Spain
| | - Jimena Varona
- Autoimmune Disease Unit, Department of Internal Medicine, Cruces University Hospital, 48903 Barakaldo, Spain
| | - Guillermo Ruiz-Irastorza
- BioBizkaia Health Research Institute, 48903 Barakaldo, Spain
- University of the Basque Country, UPV/EHU, 48940 Leioa, Spain
- Autoimmune Disease Unit, Department of Internal Medicine, Cruces University Hospital, 48903 Barakaldo, Spain
| | - Igor Horrillo
- BioBizkaia Health Research Institute, 48903 Barakaldo, Spain
- University of the Basque Country, UPV/EHU, 48940 Leioa, Spain
- Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM ISCIII, 48940 Leioa, Spain
| | - J Javier Meana
- BioBizkaia Health Research Institute, 48903 Barakaldo, Spain
- University of the Basque Country, UPV/EHU, 48940 Leioa, Spain
- Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM ISCIII, 48940 Leioa, Spain
| | | | - Rafael Segarra
- BioBizkaia Health Research Institute, 48903 Barakaldo, Spain
- University of the Basque Country, UPV/EHU, 48940 Leioa, Spain
- Department of Psychiatry, Cruces University Hospital, 48903 Barakaldo, Spain
- Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM ISCIII, 48940 Leioa, Spain
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He M, Hettinghouse A, Bi Y, Chen Y, Liu C. Progranulin mediates the onset of pristane induced systemic lupus erythematosus. Adv Rheumatol 2024; 64:67. [PMID: 39252120 DOI: 10.1186/s42358-024-00405-8] [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: 07/16/2023] [Accepted: 08/25/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUNDS Progranulin (PGRN) is a growth factor-like molecule with diverse roles in homeostatic and pathogenic processes including the control of immune and inflammatory responses. Pathogenic inflammation is a hallmark of systemic lupus erythematosus (SLE) and elevated serum levels of PGRN has been evaluated as a biomarker of disease activity in SLE. However, the role of PGRN in SLE has not been fully investigated. This study is aimed to determine the potential involvements of PGRN in SLE. METHODS Wild type (WT) and PGRN knockout (PGRN-/-) C57BL/6 mice received intraperitoneal injection of pristane for induction of a murine model of SLE. Sera were collected every biweekly and levels of anti-dsDNA antibody, IgG, and inflammatory factors were measured. Mice were sacrificed 5 months later and the renal lesions, as well as the proportions of T cell subtypes in the spleen were analyzed. RESULTS Following exposure to pristane, PGRN-/- mice generated significantly lower levels of anti-dsDNA antibody and IgG relative to WT mice. PGRN-/- mouse kidneys had less IgG and collagen deposition compared with WT mice after pristane injection. CONCLUSION The results indicate that PGRN participates in inflammatory response and renal damage in pristane induced SLE models, suggesting that PGRN mediates the onset of SLE.
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Affiliation(s)
- Michun He
- Department of Orthopaedic Surgery, New York University Medical Center, New York, NY, 10003, USA.
- Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, PR China.
| | - Aubryanna Hettinghouse
- Department of Orthopaedic Surgery, New York University Medical Center, New York, NY, 10003, USA
| | - Yufei Bi
- Department of Orthopaedic Surgery, New York University Medical Center, New York, NY, 10003, USA
| | - Yuehong Chen
- Department of Orthopaedic Surgery, New York University Medical Center, New York, NY, 10003, USA
| | - Chuanju Liu
- Department of Orthopaedic Surgery, New York University Medical Center, New York, NY, 10003, USA
- Department of Cell Biology, New York University School of Medicine, New York, NY, 10016, USA
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Zhang X, Lin G, Zhang Q, Wu H, Xu W, Wang Z, He Z, Su L, Zhuang Y, Gong A. The rs3918188 and rs1799983 loci of eNOS gene are associated with susceptibility in patients with systemic lupus erythematosus in Northeast China. Sci Rep 2024; 14:20803. [PMID: 39242633 PMCID: PMC11379712 DOI: 10.1038/s41598-024-70711-0] [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: 10/20/2023] [Accepted: 08/20/2024] [Indexed: 09/09/2024] Open
Abstract
To investigate the association between single nucleotide polymorphism (SNP) at the rs3918188, rs1799983 and rs1007311 loci of the endothelial nitric oxide synthase (eNOS) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in northeastern China. The base distribution of eNOS gene rs3918188, rs1799983 and rs1007311 in 1712 human peripheral blood samples from Northeast China was detected by SNaPshot sequencing technology. The correlation between genotype, allele and gene model of these loci of the eNOS gene and the genetic susceptibility to SLE was investigated by logistic regression analysis. The results of the differences in the frequency distribution of their gene models were visualised using R 4.3.2 software. Finally, HaploView 4.2 software was used to analyse the relationship between the haplotypes of the three loci mentioned above and the genetic susceptibility to SLE. A multifactor dimensionality reduction (MDR) analysis was used to determine the best SNP-SNP interaction model. The CC genotype and C allele at the rs3918188 locus may be a risk factor for SLE (CC vs AA: OR = 1.827, P < 0.05; C vs A: OR = 1.558, P < 0.001), and this locus increased the risk of SLE in the dominant model and the recessive model (AC + CC vs AA: OR = 1.542, P < 0.05; CC vs AA + AC: OR = 1.707, P < 0.001), while the risk of SLE was reduced in the overdominant model (AC vs AA + CC: OR = 0.628, P < 0.001). The GT genotype and T allele at locus rs1799983 may be a protective factor for SLE (GT vs GG: OR = 0.328, P < 0.001; T vs G: OR = 0.438, P < 0.001) and this locus reduced the risk of SLE in the overdominant model (GT vs GG + TT: OR = 0.385, P < 0.001). There is a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene. Among them, the formed haplotype AG increased the risk of SLE compared to GG. AT and GT decreased the risk of SLE compared to GG. In this study, the eNOS gene rs3918188 and rs1799983 loci were found to be associated with susceptibility to SLE. This helps to deeply explore the mechanism of eNOS gene and genetic susceptibility to SLE. It provides a certain research basis for the subsequent exploration of the molecular mechanism of these loci and SLE, as well as the early diagnosis, treatment and prognosis of SLE.
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Affiliation(s)
- Xuan Zhang
- College of Traditional Chinese Medicine, Hainan Medical University, Haikou, 571199, China
| | - Guiling Lin
- College of Traditional Chinese Medicine, Hainan Medical University, Haikou, 571199, China
| | - Qi Zhang
- Heilongjiang Academy of Chinese Medicine, Harbin, 150036, Heilongjiang, China
| | - Huitao Wu
- Heilongjiang Academy of Chinese Medicine, Harbin, 150036, Heilongjiang, China
| | - Wenlu Xu
- College of Traditional Chinese Medicine, Hainan Medical University, Haikou, 571199, China
| | - Zhe Wang
- College of Traditional Chinese Medicine, Hainan Medical University, Haikou, 571199, China
| | - Ziman He
- Heilongjiang Academy of Chinese Medicine, Harbin, 150036, Heilongjiang, China
| | - Linglan Su
- Heilongjiang Academy of Chinese Medicine, Harbin, 150036, Heilongjiang, China
| | - Yanping Zhuang
- International Research Center for Aging and Cancer, Hainan Medical University, Haikou, 571199, Hainan, China.
| | - Aimin Gong
- College of Traditional Chinese Medicine, Hainan Medical University, Haikou, 571199, China.
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Guo Q, Fan YN, Xie M, Wang QN, Li J, Liu S, Wang X, Yu D, Zou Z, Gao G, Zhang Q, Hao F, Feng J, Yang R, Wang M, Fu H, Bao X, Duan L. Exploring the transcriptomic landscape of moyamoya disease and systemic lupus erythematosus: insights into crosstalk genes and immune relationships. Front Immunol 2024; 15:1456392. [PMID: 39290707 PMCID: PMC11405312 DOI: 10.3389/fimmu.2024.1456392] [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: 06/28/2024] [Accepted: 08/19/2024] [Indexed: 09/19/2024] Open
Abstract
Background Systemic Lupus Erythematosus (SLE) is acknowledged for its significant influence on systemic health. This study sought to explore potential crosstalk genes, pathways, and immune cells in the relationship between SLE and moyamoya disease (MMD). Methods We obtained data on SLE and MMD from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify common genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these shared genes. Hub genes were further selected through the least absolute shrinkage and selection operator (LASSO) regression, and a receiver operating characteristic (ROC) curve was generated based on the results of this selection. Finally, single-sample Gene Set Enrichment Analysis (ssGSEA) was utilized to assess the infiltration levels of 28 immune cells in the expression profile and their association with the identified hub genes. Results By intersecting the important module genes from WGCNA with the DEGs, the study highlighted CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P as key crosstalk genes linking SLE and MMD. GO analysis indicated that these shared genes were predominantly enriched in immune system process and immune response. LASSO analysis identified MPZL3 as the optimal shared diagnostic biomarkers for both SLE and MMD. Additionally, the analysis of immune cell infiltration revealed the significant involvement of activation of T and monocytes cells in the pathogenesis of SLE and MMD. Conclusion This study is pioneering in its use of bioinformatics tools to explore the close genetic relationship between MMD and SLE. The genes CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P have been identified as key crosstalk genes that connect MMD and SLE. Activation of T and monocytes cells-mediated immune responses are proposed to play a significant role in the association between MMD and SLE.
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Affiliation(s)
- Qingbao Guo
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Yan-Na Fan
- Department of Radiation Oncology, Senior Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Manli Xie
- Department of Occupational Diseases, Xi'an Central Hospital, Xi'an, Shanxi, China
| | - Qian-Nan Wang
- Department of Neurosurgery, The Eighth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Jingjie Li
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Simeng Liu
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Xiaopeng Wang
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Dan Yu
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Zhengxing Zou
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Gan Gao
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Qian Zhang
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Fangbin Hao
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Jie Feng
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Rimiao Yang
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Minjie Wang
- Medical School of Chinese PLA, Beijing, China
- Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Heguan Fu
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Xiangyang Bao
- Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Lian Duan
- Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
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Rosta K, Heinzl F, Kuczwara V, Schindler S, Falcone V, Catic A, Riedmann M, Leitner H, Simader E, Ritschl V, Stamm T, Szlatinay A, Mandl P, Mazzucato-Puchner A. Pregnancy outcomes in patients with systemic lupus erythematosus compared to a high-risk tertiary cohort and to standard population from the Austrian birth registry. Acta Obstet Gynecol Scand 2024; 103:1820-1828. [PMID: 38943224 PMCID: PMC11324932 DOI: 10.1111/aogs.14880] [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: 12/26/2023] [Revised: 04/24/2024] [Accepted: 05/06/2024] [Indexed: 07/01/2024]
Abstract
INTRODUCTION Women with systemic lupus erythematosus (SLE) have a higher risk for fetal and maternal complications. We aimed to investigate maternal and fetal complications in pregnant women with SLE compared to a high-risk pregnancy cohort (HR) from a tertiary university center and a standard-risk general population (SR) from the Austrian Birth Registry. MATERIAL AND METHODS In this retrospective data analysis, we compared the incidence of fetal/neonatal and maternal complications of pregnancies and deliveries of women with SLE to age, body mass index and delivery date-matched high-risk pregnancies from the same department, a progressive tertiary obstetric center and to a group of women, who represent pregnancies with standard obstetric risk from the Austrian Birth Registry. RESULTS One hundred women with SLE were compared to 300 women with high-risk pregnancies and 207 039 women with standard-risk pregnancies. The incidence of composite maternal complications (preeclampsia, Hemolysis, Elevated Liver enzymes and Low Platelets [HELLP] syndrome, pregnancy-related hypertension, gestational diabetes mellitus, maternal death, thromboembolic events) was significantly higher in the SLE as compared to the SR group (28% vs. 6.28% SLE vs. SR, p = 0.001). There was no difference between the SLE and the HR groups (28% vs. 29.6% SLE vs. HR group, p = 0.80). The incidence of composite fetal complications (preterm birth before 37 weeks of gestation, stillbirths, birthweight less than 2500 g, fetal growth restriction, large for gestational age, admission to neonatal intensive care unit, 5-min Apgar <7) was also higher in the SLE than in the SR group (55% vs. 25.54% SLE vs. SR p < 0.001) while the higher incidence of adverse fetal outcome was detected in the HR than in the SLE group (55% vs. 75% SLE vs. HR group, p = 0.0005). CONCLUSIONS Although composite fetal risk is higher in the SLE group than in the general population, it is still significantly lower as compared to high-risk pregnant women at a tertiary obstetric center. Prepregnancy counseling of women with SLE should put fetal and maternal risk in perspective, not only in relation to healthy, low risk cohorts, but also compared to mixed HR populations.
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Affiliation(s)
- Klara Rosta
- Department of Obstetrics and Gynecology, Clinical Division of Gynecological Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria
| | - Florian Heinzl
- Department of Obstetrics and Gynecology, Clinical Division of Gynecological Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria
| | - Valerie Kuczwara
- Department of Obstetrics and Gynecology, Clinical Division of Gynecological Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria
| | - Stefanie Schindler
- Department of Obstetrics and Gynecology, Clinical Division of Gynecological Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria
| | - Veronica Falcone
- Department of Obstetrics and Gynecology, Clinical Division of Gynecological Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria
| | - Anja Catic
- Department of Obstetrics and Gynecology, Clinical Division of Gynecological Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria
| | - Marina Riedmann
- Department of Clinical Epidemiology, Tyrolean Federal Institute for Integrated Care, Tirol Kliniken GmbH, Innsbruck, Austria
| | - Hermann Leitner
- Department of Clinical Epidemiology, Tyrolean Federal Institute for Integrated Care, Tirol Kliniken GmbH, Innsbruck, Austria
| | - Elisabeth Simader
- Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
| | - Valentin Ritschl
- Center for Medical Data Science, Institute for Outcomes Research, Medical University of Vienna, Vienna, Austria
- Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna, Austria
| | - Tanja Stamm
- Center for Medical Data Science, Institute for Outcomes Research, Medical University of Vienna, Vienna, Austria
- Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna, Austria
| | - Alexandra Szlatinay
- Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
| | - Peter Mandl
- Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
| | - Antonia Mazzucato-Puchner
- Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
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44
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Houen G. Auto-immuno-deficiency syndromes. Autoimmun Rev 2024; 23:103610. [PMID: 39209011 DOI: 10.1016/j.autrev.2024.103610] [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: 06/10/2024] [Revised: 08/26/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
Autoimmune diseases constitute a broad, heterogenous group with many diverse and often overlapping symptoms. Even so, they are traditionally classified as either systemic, rheumatic diseases or organ-directed diseases. Several theories exist about autoimmune diseases, including defective self-recognition, altered self, molecular mimicry, bystander activation and epitope spreading. While there is no consensus about these theories, it is generally accepted that genetic, pre-disposing factors in combination with environmental factors can result in autoimmune disease. The relative contribution of genetic and environmental factors varies between diseases, as does the significance of individual contributing factors within related diseases. Among the genetic factors, molecules involved in antigen (Ag) recognition, processing, and presentation stand out (e.g., MHC I and II) together with molecules involved in immune signaling and regulation of cellular interactions (i.e., immuno-phenotypes). Also, various immuno-deficiencies have been linked to development of autoimmune diseases. Among the environmental factors, infections (e.g., viruses) have attracted most attention, but factors modulating the immune system have also been the subject of much research (e.g., sunlight and vitamin D). Multiple sclerosis currently stands out due to a very strong and proven association with Epstein-Barr virus infection, notably in cases of late infection and in cases of EBV-associated mononucleosis. Thus, a common picture is emerging that both systemic and organ-directed autoimmune diseases may appropriately be described as auto-immuno-deficiency syndromes (AIdeSs), a concept that emphasizes and integrates existing knowledge on the role of immuno-deficiencies and chronic infections with development of overlapping disease syndromes with variable frequencies of autoantibodies and/or autoreactive T cells. This review integrates and exemplifies current knowledge on the interplay of genetically determined immuno-phenotypes and chronic infections in the development of AIdeSs.
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Affiliation(s)
- Gunnar Houen
- Department of Neurology and Translational Research Center (TRACE), Rigshospitalet, Nordstjernevej 42, DK-2600 Glostrup, Denmark; Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
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Altabás-González I, Rua-Figueroa I, Mouriño C, Roberts K, Jimenez N, Martinez-Barrio J, Galindo M, Calvo Alén J, Pérez VDC, Uriarte Itzazelaia E, Tomero E, Freire-González M, Martínez Taboada V, Salgado E, Vela P, Fernandez-Nebro A, Olivé A, Narváez J, Menor-Almagro R, Soler GS, Hernández-Beriain JÁ, Manero J, Aurrecoechea E, Ibarguengoitia-Barrena O, Montilla C, Bonilla G, Torrente-Segarra V, Cacheda AP, García-Villanueva MJ, Moriano-Morales C, Manteca CF, Lozano-Rivas N, Bohórquez C, Pego-Reigosa JM. Damage in a large systemic lupus erythematosus cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER) with emphasis on the cardiovascular system: a longitudinal analysis. Lupus Sci Med 2024; 11:e001064. [PMID: 39097409 PMCID: PMC11331961 DOI: 10.1136/lupus-2023-001064] [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: 10/19/2023] [Accepted: 06/18/2024] [Indexed: 08/05/2024]
Abstract
OBJECTIVE To assess organ damage, with emphasis on the cardiovascular system, over the different stages of the disease in a large SLE cohort. METHODS Multicentre, longitudinal study of a cohort of 4219 patients with SLE enrolled in the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We longitudinally analysed SDI (globally and for each domain) over time only in the 1274 patients whose dates of damage events had been recorded. RESULTS During the first year after diagnosis of SLE, 20% of the 1274 patients presented with new damage manifestations. At years 2 and 3, new damage was recorded in 11% and 9% of patients. The annual percentage of patients with new damage after year 5 decreased to 5%. In the first year with the disease, most damage was accumulated in the musculoskeletal, neuropsychiatric and renal systems; in later stages, most damage was in the musculoskeletal, ocular and cardiovascular systems. Considering 'cerebrovascular accident' and 'claudication for 6 months' as cardiovascular items, the cardiovascular system was the second most affected system during the early stages of SLE, with 19% of the patients who presented with damage affected at first year after diagnosis. During the late stages, 20-25% of the patients presenting with new damage did so in this modified cardiovascular domain of the SDI. CONCLUSIONS New damage occurs mainly during the first year following diagnosis of SLE. Cardiovascular damage is relevant in both the early and the late stages of the disease. Strategies to prevent cardiovascular damage should be implemented early after diagnosis of SLE.
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Affiliation(s)
- Irene Altabás-González
- Rheumatology Department, Vigo University Hospital Group, Vigo, Spain
- IRIDIS Group (Investigation in Rheumatology and Immune-Diseases), Galicia Sur Health Research Institute, Vigo, Spain
| | - Iñigo Rua-Figueroa
- Rheumatology, Hospital Universitario de Gran Canaria Dr Negrin, Las Palmas de Gran Canaria, Spain
| | - Coral Mouriño
- Rheumatology Department, Vigo University Hospital Group, Vigo, Spain
| | - Karen Roberts
- Rheumatology, Instituto de Investigación, Galicia Sur, External Statistical Advisor, Rosario, Argentina
| | - Norman Jimenez
- IRIDIS Group (Investigation in Rheumatology and Immune-Diseases), Galicia Sur Health Research Institute, Vigo, Spain
| | | | - María Galindo
- Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain
| | - Jaime Calvo Alén
- Rheumatology, Hospital Universitario Araba, Vitoria-Gasteiz, Spain
| | - Victor del Campo Pérez
- IRIDIS Group (Investigation in Rheumatology and Immune-Diseases), Galicia Sur Health Research Institute, Vigo, Spain
- Department of Epidemiology, Vigo University Hospital Group, Vigo, Spain
| | | | - Eva Tomero
- Rheumatology Department, Hospital Universitario de la Princesa, Madrid, Spain
| | | | | | - Eva Salgado
- Rheumatology, Complejo Hospitalario de Orense, Ourense, Spain
| | - Paloma Vela
- Department of Rheumatology, Hospital General Universitario de Alicante, Alicante, Spain
| | | | - Alejandro Olivé
- Rheumatology Department, Hospital Universitario Germans Trias i Pujol, Badalona, Spain
| | - Javier Narváez
- Rheumatology, Hospital Universitario de Bellvitge, Hospitalet de LLobregat, Spain
| | | | | | | | - Javier Manero
- Department of Rheumatology, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | | | | | | | - Gema Bonilla
- Rheumatology, La Paz University Hospital, Madrid, Spain
| | | | - Ana Paula Cacheda
- Department of Rheumatology, Hospital Son Llatzer, Palma de Mallorca, Spain
| | | | | | | | | | - Cristina Bohórquez
- Department of Rheumatology, Hospital Universitario Príncipe de Asturias, Alcala de Henares, Spain
| | - José M Pego-Reigosa
- Rheumatology Department, Vigo University Hospital Group, Vigo, Spain
- IRIDIS Group (Investigation in Rheumatology and Immune-Diseases), Galicia Sur Health Research Institute, Vigo, Spain
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Swain HN, Boyce PD, Bromet BA, Barozinksy K, Hance L, Shields D, Olbricht GR, Semon JA. Mesenchymal stem cells in autoimmune disease: A systematic review and meta-analysis of pre-clinical studies. Biochimie 2024; 223:54-73. [PMID: 38657832 DOI: 10.1016/j.biochi.2024.04.009] [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: 01/30/2024] [Revised: 04/08/2024] [Accepted: 04/20/2024] [Indexed: 04/26/2024]
Abstract
Mesenchymal Stem Cells (MSCs) are of interest in the clinic because of their immunomodulation capabilities, capacity to act upstream of inflammation, and ability to sense metabolic environments. In standard physiologic conditions, they play a role in maintaining the homeostasis of tissues and organs; however, there is evidence that they can contribute to some autoimmune diseases. Gaining a deeper understanding of the factors that transition MSCs from their physiological function to a pathological role in their native environment, and elucidating mechanisms that reduce their therapeutic relevance in regenerative medicine, is essential. We conducted a Systematic Review and Meta-Analysis of human MSCs in preclinical studies of autoimmune disease, evaluating 60 studies that included 845 patient samples and 571 control samples. MSCs from any tissue source were included, and the study was limited to four autoimmune diseases: multiple sclerosis, rheumatoid arthritis, systemic sclerosis, and lupus. We developed a novel Risk of Bias tool to determine study quality for in vitro studies. Using the International Society for Cell & Gene Therapy's criteria to define an MSC, most studies reported no difference in morphology, adhesion, cell surface markers, or differentiation into bone, fat, or cartilage when comparing control and autoimmune MSCs. However, there were reported differences in proliferation. Additionally, 308 biomolecules were differentially expressed, and the abilities to migrate, invade, and form capillaries were decreased. The findings from this study could help to explain the pathogenic mechanisms of autoimmune disease and potentially lead to improved MSC-based therapeutic applications.
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Affiliation(s)
- Hailey N Swain
- Department of Biological Sciences, Missouri University of Science and Technology, USA
| | - Parker D Boyce
- Department of Biological Sciences, Missouri University of Science and Technology, USA
| | - Bradley A Bromet
- Department of Biological Sciences, Missouri University of Science and Technology, USA
| | - Kaiden Barozinksy
- Department of Biological Sciences, Missouri University of Science and Technology, USA
| | - Lacy Hance
- Department of Biological Sciences, Missouri University of Science and Technology, USA
| | - Dakota Shields
- Department of Mathematics and Statistics, Missouri University of Science and Technology, USA
| | - Gayla R Olbricht
- Department of Mathematics and Statistics, Missouri University of Science and Technology, USA
| | - Julie A Semon
- Department of Biological Sciences, Missouri University of Science and Technology, USA.
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Fijałkowska A, Wojtania J, Woźniacka A, Robak E. Psoriasis and Lupus Erythematosus-Similarities and Differences between Two Autoimmune Diseases. J Clin Med 2024; 13:4361. [PMID: 39124628 PMCID: PMC11312967 DOI: 10.3390/jcm13154361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 07/19/2024] [Accepted: 07/24/2024] [Indexed: 08/12/2024] Open
Abstract
Systemic lupus erythematosus (SLE) and psoriasis (Ps) are two clinically distinct diseases with different pathogenesis. However, recent studies indicate some similarities in both clinical presentation and pathogenetic mechanisms. The coexistence of both entities is very uncommon and has not been fully elucidated. Thus, it remains a diagnostic and therapeutic challenge. In fact, drugs used in SLE can induce psoriatic lesions, whereas phototherapy effective in Ps is an important factor provoking skin lesions in patients with SLE. The aim of this work is to discuss in detail the common pathogenetic elements and the therapeutic options effective in both diseases.
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Affiliation(s)
| | | | | | - Ewa Robak
- Department of Dermatology and Venereology, Medical University of Lodz, Haller sq. 1, 90-647 Lodz, Poland; (A.F.); (J.W.); (A.W.)
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48
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Ziaka M, Exadaktylos A. Gut-derived immune cells and the gut-lung axis in ARDS. Crit Care 2024; 28:220. [PMID: 38965622 PMCID: PMC11225303 DOI: 10.1186/s13054-024-05006-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 06/26/2024] [Indexed: 07/06/2024] Open
Abstract
The gut serves as a vital immunological organ orchestrating immune responses and influencing distant mucosal sites, notably the respiratory mucosa. It is increasingly recognized as a central driver of critical illnesses, with intestinal hyperpermeability facilitating bacterial translocation, systemic inflammation, and organ damage. The "gut-lung" axis emerges as a pivotal pathway, where gut-derived injurious factors trigger acute lung injury (ALI) through the systemic circulation. Direct and indirect effects of gut microbiota significantly impact immune responses. Dysbiosis, particularly intestinal dysbiosis, termed as an imbalance of microbial species and a reduction in microbial diversity within certain bodily microbiomes, influences adaptive immune responses, including differentiating T regulatory cells (Tregs) and T helper 17 (Th17) cells, which are critical in various lung inflammatory conditions. Additionally, gut and bone marrow immune cells impact pulmonary immune activity, underscoring the complex gut-lung interplay. Moreover, lung microbiota alterations are implicated in diverse gut pathologies, affecting local and systemic immune landscapes. Notably, lung dysbiosis can reciprocally influence gut microbiota composition, indicating bidirectional gut-lung communication. In this review, we investigate the pathophysiology of ALI/acute respiratory distress syndrome (ARDS), elucidating the role of immune cells in the gut-lung axis based on recent experimental and clinical research. This exploration aims to enhance understanding of ALI/ARDS pathogenesis and to underscore the significance of gut-lung interactions in respiratory diseases.
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Affiliation(s)
- Mairi Ziaka
- Clinic of Geriatric Medicine, Center of Geriatric Medicine and Rehabilitation, Kantonsspital Baselland, Bruderholz, Switzerland.
- Department of Emergency Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland.
| | - Aristomenis Exadaktylos
- Department of Emergency Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland
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49
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Forsyth KS, Jiwrajka N, Lovell CD, Toothacre NE, Anguera MC. The conneXion between sex and immune responses. Nat Rev Immunol 2024; 24:487-502. [PMID: 38383754 PMCID: PMC11216897 DOI: 10.1038/s41577-024-00996-9] [Citation(s) in RCA: 44] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2024] [Indexed: 02/23/2024]
Abstract
There are notable sex-based differences in immune responses to pathogens and self-antigens, with female individuals exhibiting increased susceptibility to various autoimmune diseases, and male individuals displaying preferential susceptibility to some viral, bacterial, parasitic and fungal infections. Although sex hormones clearly contribute to sex differences in immune cell composition and function, the presence of two X chromosomes in female individuals suggests that differential gene expression of numerous X chromosome-linked immune-related genes may also influence sex-biased innate and adaptive immune cell function in health and disease. Here, we review the sex differences in immune system composition and function, examining how hormones and genetics influence the immune system. We focus on the genetic and epigenetic contributions responsible for altered X chromosome-linked gene expression, and how this impacts sex-biased immune responses in the context of pathogen infection and systemic autoimmunity.
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Affiliation(s)
- Katherine S Forsyth
- Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Nikhil Jiwrajka
- Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Division of Rheumatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Claudia D Lovell
- Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Natalie E Toothacre
- Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Montserrat C Anguera
- Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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50
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Quesada S, Rosso AD, Mascardi F, Soler-Rivero V, Aguilera P, Mascuka SN, Boiro A, Arenielo E, Vijoditz G, Ferreyra-Mufarregue LR, Caputo MF, Cimolai MC, Coluccio Leskow F, Penas-Steinhardt A, Belforte FS. Integrative analysis of systemic lupus erythematosus biomarkers: Role of fecal hsa-mir-223-3p and gut microbiota in transkingdom dynamics. Mol Immunol 2024; 171:77-92. [PMID: 38795687 DOI: 10.1016/j.molimm.2024.05.004] [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: 01/26/2024] [Revised: 04/20/2024] [Accepted: 05/10/2024] [Indexed: 05/28/2024]
Abstract
Systemic lupus erythematosus (SLE) involves a florid set of clinical manifestations whose autoreactive origin is characterized by an overactivation of the immune system and the production of a large number of autoantibodies. Because it is a complex pathology with an inflammatory component, its pathogenesis is not yet fully understood, assuming both genetic and environmental predisposing factors. Currently, it is known that the role of the human microbiome is crucial in maintaining the transkingdom balance between commensal microorganisms and the immune system. In the present work we study the intestinal microbiota of Argentine patients with different stages of SLE receiving or not different treatments. Microbiota composition and fecal miRNAs were assessed by 16 S sequencing and qPCR. hsa-miR-223-3p, a miRNA involved in several inflammation regulation pathways, was found underexpressed in SLE patients without immunosuppressive treatment. In terms of microbiota there were clear differences in population structure (Weighted and Unweighted Unifrac distances, p-value <0.05) and core microbiome between cases and controls. In addition, Collinsella, Bifidobacterium, Streptococcus genera and aromatics degradation metabolisms were overrepresented in the SLE group. Medical treatment was also determinant as several microbial metabolic pathways were influenced by immunosuppressive therapy. Particularly, allantoin degradation metabolism was differentially expressed in the group of patients receiving immunosuppressants. Finally, we performed a logistic regression model (LASSO: least absolute shrinkage and selection operator) considering the expression levels of the fecal hsa-miR223-3p; the core microbiota; the differentially abundant bacterial taxa and the differentially abundant metabolic pathways (p<0.05). The model predicted that SLE patients could be associated with greater relative abundance of the formaldehyde oxidation pathway (RUMP_PWY). On the contrary, the preponderance of the ketodeoxyoctonate (Kdo) biosynthesis and activation route (PWY_1269) and the genera Lachnospiraceae_UCG_004, Lachnospira, Victivallis and UCG_003 (genus belonging to the family Oscillospiraceae of the class Clostridia) were associated with a control phenotype. Overall, the present work could contribute to the development of integral diagnostic tools for the comprehensive phenotyping of patients with SLE. In this sense, studying the commensal microbial profile and possible pathobionts associated with SLE in our population proposes more effective and precise strategies to explore possible treatments based on the microbiota of SLE patients.
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Affiliation(s)
- Sofía Quesada
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina; Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
| | - Ayelén Daiana Rosso
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina; Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Instituto de Ecología y Desarrollo Sustentable (INEDES-CONICET-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina
| | - Florencia Mascardi
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB), CONICET, Instituto Universitario del Hospital Italiano (IUHI), Hospital Italiano de Buenos Aires (HIBA), Buenos Aires, Argentina
| | - Valeria Soler-Rivero
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina; Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina
| | - Pablo Aguilera
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
| | - Sebastian Nicolas Mascuka
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina; Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina
| | - Andrea Boiro
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina
| | - Evangelina Arenielo
- Sección Inmunología, Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina
| | - Gustavo Vijoditz
- Sección Inmunología, Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina
| | | | - Marina Flavia Caputo
- Sección Inmunología, Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina
| | - María Cecilia Cimolai
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina
| | - Federico Coluccio Leskow
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
| | - Alberto Penas-Steinhardt
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina; Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Instituto Universitario de Ciencias de la Salud, Fundación H.A. Barceló, Ciudad Autónoma de Buenos Aires, Argentina
| | - Fiorella Sabrina Belforte
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina; Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Instituto de Ecología y Desarrollo Sustentable (INEDES-CONICET-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján, Argentina.
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