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Huang H, Zhang LL, Zhou J, Li M, Zeng X, Xu D. Bibliometric insights into systemic sclerosis with renal involvement: trends, contributions, and future directions. Ren Fail 2025; 47:2463583. [PMID: 39995144 PMCID: PMC11864008 DOI: 10.1080/0886022x.2025.2463583] [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: 12/17/2024] [Revised: 01/25/2025] [Accepted: 02/01/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Renal involvement is not uncommon in patients with systemic sclerosis (SSc) and presents in various forms, particularly progressing to scleroderma renal crisis (SRC), which is associated with poor prognosis. Therefore, understanding the research trends in this field is critical for advancing clinical management and therapeutic strategies. METHODS A bibliometric analysis was conducted using the Web of Science Core Collection, examining publications related to SSc and renal involvement from January 2000 to November 2024. We analyzed publication trends, key contributors, institutions, and countries. RESULTS A total of 1,339 publications were identified in the field of SSc and renal involvement, demonstrating an upward trend in publication volume from 2000 to 2024. These articles have been cited a total of 61,234 times, with the majority of contributions coming from the United States, Italy, and East Asian countries. The University of Michigan and University College London were particularly prominent in terms of both publication volume and collaboration networks. Keyword analysis revealed a shift in research focus, with increasing attention on clinical aspects, pathophysiological mechanisms, and vascular complications. CONCLUSIONS This study provides a comprehensive overview of the research landscape on SSc with renal involvement, highlighting the key contributors and emerging trends.
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Affiliation(s)
- Haochen Huang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Ling-ling Zhang
- Department of Rheumatology and Clinical Immunology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Jiaxin Zhou
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Mengtao Li
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Xiaofeng Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Dong Xu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China
- Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
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Chepy A, Collet A, Launay D, Dubucquoi S, Sobanski V. Autoantibodies in systemic sclerosis: From disease bystanders to pathogenic players. J Transl Autoimmun 2025; 10:100272. [PMID: 39917316 PMCID: PMC11799969 DOI: 10.1016/j.jtauto.2025.100272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 01/15/2025] [Accepted: 01/20/2025] [Indexed: 02/09/2025] Open
Abstract
Autoantibodies (Aab) are recognized as key indicators in the diagnosis, classification, and monitoring of systemic autoimmune diseases (AID). Recent studies have expanded knowledge through the discovery of new antigenic targets, advanced methods for measuring Aab levels, and understanding their possible pathogenic roles in AID. This narrative review uses systemic sclerosis (SSc) as an example to highlight the importance of Aab associated with HEp-2 immunofluorescence assay positivity (traditionally referred as antinuclear antibodies [ANA]), exploring recent developments in the field. Firstly, we outline the various types of ANA found in SSc and their links with specific disease features. Newly discovered antibodies shed light on SSc cases where Aab had previously gone unidentified. Secondly, we emphasize the necessity for novel quantitative techniques to track Aab levels over time by gathering data regarding the timing of Aab occurrence relative to SSc symptoms and the relationships between Aab concentrations and disease severity. Finally, we discuss the experimental findings suggesting a potential direct role of Aab in the development of SSc. The advancements surrounding Aab provide insights into new disease mechanisms and may lead to innovative diagnostic and treatment approaches.
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Affiliation(s)
- Aurélien Chepy
- Univ. Lille, Inserm, CHU Lille, U1286 – INFINITE – Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Département de Médecine interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), Lille, France
| | - Aurore Collet
- Univ. Lille, Inserm, CHU Lille, U1286 – INFINITE – Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Institut d’Immunologie, Lille, France
| | - David Launay
- Univ. Lille, Inserm, CHU Lille, U1286 – INFINITE – Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Département de Médecine interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), Lille, France
| | - Sylvain Dubucquoi
- Univ. Lille, Inserm, CHU Lille, U1286 – INFINITE – Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Institut d’Immunologie, Lille, France
| | - Vincent Sobanski
- Univ. Lille, Inserm, CHU Lille, U1286 – INFINITE – Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Département de Médecine interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), Lille, France
- Institut Universitaire de France (IUF), Paris, France
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Wang P, Wu D, Gong Z, Adu-Gyamfi M, Kamhieh-Milz J, da Fonseca DLM, Sürücü G, Ashraf MI, Heidecke H, Sikorska D, Cabral-Marques O, Moll G, Riemekasten G, Witowski J, Catar R. Stimulation of endothelin-1 production by autoantibodies present in patients with scleroderma renal crisis. Clin Immunol 2025; 273:110454. [PMID: 39956166 DOI: 10.1016/j.clim.2025.110454] [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: 10/04/2024] [Revised: 02/11/2025] [Accepted: 02/13/2025] [Indexed: 02/18/2025]
Abstract
Here, we investigate how autoantibodies against G protein-coupled receptors (GPCRs) on endothelial cells, which are present in patients with scleroderma renal crisis (SRC) impact on endothelin-1 (ET-1) production in human microvascular endothelial cells (HMECs). To this end, serum IgG fraction was isolated from SRC patients and applied to HMECs in culture. Compared to cells treated with either plain control medium or serum IgG from healthy individuals, exposure of HMECs to SRC-IgG resulted in a time- and concentration-dependent increase in ET-1 expression and release. This effect could be blocked by the protease activated receptor 1 (PAR1) inhibitor and mimicked by thrombin, the PAR1 activator. Transcription factor C-FOS/AP-1 and tissue factor (TF) were identified as mediators of these responses. Thus, it can be concluded that serum IgG fraction from SRC patients stimulates endothelial cells to produce ET-1, acting through PAR1 in cooperation with TF.
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Affiliation(s)
- Pinchao Wang
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Dashan Wu
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Zexian Gong
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Michael Adu-Gyamfi
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Julian Kamhieh-Milz
- Department of Transfusion Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | | | - Gülistan Sürücü
- Department of Transfusion Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Muhammad I Ashraf
- Department of Surgery, Charité Universitätsmedizin Berlin, Berlin, Germany
| | | | - Dorota Sikorska
- Department of Rheumatology, Rehabilitation and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Otavio Cabral-Marques
- Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Department of Medicine, Division of Molecular Medicine, Laboratory of Medical Investigation 29, University of São Paulo, Sao Paulo, SP, Brazil; Instituto D'Or de Ensino e Pesquisa, Sao Paulo, Brazil
| | - Guido Moll
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany; BIH Center for Regenerative Therapies and Berlin-Brandenburg, School for Regenerative Therapies and Julius Wolff Institute, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Gabriela Riemekasten
- Department of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany
| | - Janusz Witowski
- Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland.
| | - Rusan Catar
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
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Maltez N, Wang M, Wells GA, Tugwell P, Baron M, Marjanovic Z, Lansiaux P, Farge D, Hudson M. Improvement in Skin Fibrosis and Lung Function with Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis. Transplant Cell Ther 2025:S2666-6367(25)01011-5. [PMID: 39938806 DOI: 10.1016/j.jtct.2025.02.005] [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: 09/06/2024] [Revised: 01/21/2025] [Accepted: 02/04/2025] [Indexed: 02/14/2025]
Abstract
Systemic sclerosis (SSc) is a severe, progressive disease with limited treatment options. Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to be an effective treatment for rapidly progressive SSc. The objective of this study was to evaluate the effectiveness of AHSCT for SSc compared to real-world clinical care. SSc patients from France who underwent AHSCT were compared to patients from Canada who met criteria for AHSCT (as defined in the ASTIS trial) but received conventional care. The primary outcome was overall survival. Secondary outcomes included modified Rodnan skin score (mRSS) and forced vital capacity (FVC). Overall survival was estimated by Kaplan-Meier survival curves. Measures of mRSS and FVC were compared using linear regression models. Analyses were adjusted for baseline scores and incorporated stabilized inverse probability of treatment weights to account for confounding by indication. Propensity scores were estimated using logistic regression. Forty-one AHSCT patients and 85 conventional care patients were compared. AHSCT was associated with a suggestive, though not statistically significant trend toward improvement in overall survival (log-rank P = .115). In follow-up, the mRSS was lower with AHSCT compared to conventional care: between group difference of 8.81; P ≤ .0001 at 12 months and 11.28; P = .011 at 60 months. There was no significant difference in FVC between groups at 12 months but at 24 months, AHSCT was associated with a higher FVC (between group difference of 10.53 (P = .05)). This study demonstrates with real-world long-term data that compared with conventional care, treatment with AHSCT may offer superior outcomes for SSc patients.
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Affiliation(s)
- Nancy Maltez
- School of Epidemiology and Public Health, University of Ottawa, The Ottawa Hospital, Division of Rheumatology, Ottawa, Canada.
| | | | - Georges A Wells
- Cardiovascular Research Methods Centre, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
| | - Peter Tugwell
- School of Epidemiology and Public Health, University of Ottawa, The Ottawa Hospital, Division of Rheumatology, Ottawa, Canada
| | - Murray Baron
- McGill University, Jewish General Hospital, Montreal, Canada
| | | | - Pauline Lansiaux
- Université de Paris, IRSL, Recherche clinique appliquée à l'hématologie, Centre de Référence des Maladies auto-immunes systémiques Rares d'Ile-de-France, AP-HP, Hôpital St-Louis, Paris, France
| | - Dominique Farge
- Université de Paris, IRSL, Recherche clinique appliquée à l'hématologie, Centre de Référence des Maladies auto-immunes systémiques Rares d'Ile-de-France, AP-HP, Hôpital St-Louis, Paris, France
| | - Marie Hudson
- Lady Davis Institute, McGill University, Jewish General Hospital, Montreal, Canada
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Kotani H, Matsuda KM, Yamaguchi K, Ono C, Kogo E, Ogawa K, Kobayashi Y, Hisamoto T, Kawanabe R, Kuzumi A, Fukasawa T, Yoshizaki‐Ogawa A, Goshima N, Sato S, Yoshizaki A. Diversity and Epitope Spreading of Anti-RNA Polymerase III Antibodies in Systemic Sclerosis: A Potential Biomarker for Skin and Lung Involvement. Arthritis Rheumatol 2025; 77:67-79. [PMID: 39219033 PMCID: PMC11684998 DOI: 10.1002/art.42975] [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: 03/25/2024] [Revised: 06/07/2024] [Accepted: 08/19/2024] [Indexed: 09/04/2024]
Abstract
OBJECTIVE Epitope spreading (ES), involving autoantibodies, plays a crucial role in the development and persistence of autoimmune reactions in various autoimmune diseases. This study aimed to investigate the relationship between ES of anti-RNA polymerase III (RNAP III) antibodies (ARAs) and the clinical manifestations of systemic sclerosis (SSc). METHODS We investigated whether intermolecular ES occurs in the subunits of the RNAP III complex and whether intramolecular ES targets the major antigen, RNA polymerase III subunit A (RPC1), in patients with SSc. To achieve this, we synthesized 17 full-length subunit proteins of the RNAP III complex and 5 truncated forms of RPC1 in vitro using a wheat germ cell-free translation system. Subsequently, we prepared antigen-binding plates and measured autoantibodies in the serum of patients with SSc. RESULTS Autoantibodies against different RNAP III complex subunits were found in patients who were ARA-positive with SSc. The intermolecular ES indicators significantly correlated with the modified Rodnan skin thickness score (mRSS) and surfactant protein-D, a biomarker of interstitial lung disease. However, the extent of disease on high-resolution computed tomography or pulmonary function tests did not show any significant correlation. Intramolecular ES indicator against RPC1 were significantly correlated with mRSS and renal crisis. Furthermore, longitudinal assessment of ES in RNAP III complex subunits correlated with mRSS and exhibited potential as a disease activity biomarker. CONCLUSION Our findings indicate a correlation between ES levels and the severity of skin sclerosis or the risk of other complications in SSc. This study suggests that measuring ES in SSc serves as a novel biomarker for disease activity.
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Affiliation(s)
| | | | | | | | - Emi Kogo
- ProteoBridge CorporationKoto‐kuJapan
| | | | | | | | | | | | | | | | - Naoki Goshima
- ProteoBridge Corporation and the University of MusashinoKoto‐kuJapan
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Tonutti A, Motta F, Isailovic N, Ceribelli A, Ragusa R, Nappi E, Bonovas S, Selmi C, De Santis M. Autoantibodies, cutaneous subset and immunosuppressants contribute to the cancer risk in systemic sclerosis. RMD Open 2024; 10:e004492. [PMID: 39306344 PMCID: PMC11418480 DOI: 10.1136/rmdopen-2024-004492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 09/06/2024] [Indexed: 09/25/2024] Open
Abstract
OBJECTIVE Systemic sclerosis (SSc) is associated with an increased risk of cancer. We aimed to assess the prevalence of cancer in our cohort and to explore possible associations with clinical, immunological and treatment characteristics. METHODS Our retrospective monocentric cohort study of patients with SSc recorded prevalent and incident cases of malignancy, including those diagnosed within 3 years of the SSc onset (defined as cancer-associated scleroderma) and sought associations with the clinical characteristics and the serum autoantibody profiling performed using RNA and protein immunoprecipitation, Western-blot, immunoblot and ELISA at the time of SSc diagnosis, prior to any specific treatment. RESULTS Among 290 patients with SSc, the overall prevalence of cancer was 20%, with 8% of cases being cancer-associated scleroderma. Both conditions were more frequent in elderly patients and in patients with positive anti-Ro52 or anti-U3-RNP. Cancer-associated scleroderma was significantly more prevalent among patients negative for both anti-centromere (ACA) and anti-topoisomerase-1 (TOPO1) antibodies, especially in the case of diffuse SSc. Immunosuppressants were not significantly associated with cancer. Patients triple negative for ACA, TOPO1 and anti-RNA polymerase III antibodies had a significantly higher risk of breast cancer. CONCLUSIONS Cancer surveillance should be particularly careful in patients with diffuse SSc, increased age at disease onset and without classical SSc-related autoantibodies.
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Affiliation(s)
- Antonio Tonutti
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Francesca Motta
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Natasa Isailovic
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Angela Ceribelli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Rita Ragusa
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Emanuele Nappi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Carlo Selmi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Maria De Santis
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy
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Martel ME, Leurs A, Launay D, Behal H, Chepy A, Collet A, Sanges S, Hachulla E, Dubucquoi S, Dauchet L, Sobanski V. Prevalence of anti-Ro52-kDa/SSA (TRIM21) antibodies and associated clinical phenotype in systemic sclerosis: Data from a French cohort, a systematic review and meta-analysis. Autoimmun Rev 2024; 23:103536. [PMID: 38555075 DOI: 10.1016/j.autrev.2024.103536] [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: 01/04/2024] [Revised: 03/24/2024] [Accepted: 03/24/2024] [Indexed: 04/02/2024]
Abstract
OBJECTIVES Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a systematic review and meta-analysis of published reports and new data from our French cohort. METHODS Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719). FINDINGS In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, p = 0.006), more likely to present an associated Sjögren's syndrome (19% vs 7%, p < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, p = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, p = 0.038) or nausea/vomiting (10% vs 3%, p = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I2: 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60]). INTERPRETATION Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients.
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Affiliation(s)
- Marie-Elise Martel
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Amélie Leurs
- CH Dunkerque, Département de Médecine interne et Maladies infectieuses, F-59240 Dunkerque, France
| | - David Launay
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Hélène Behal
- CHU Lille, SEED: Statistique, évaluation, économique, data-management - Maison Régionale de la Recherche Clinique, F-59000 Lille, France
| | - Aurélien Chepy
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Aurore Collet
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Sébastien Sanges
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Eric Hachulla
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Sylvain Dubucquoi
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France
| | - Luc Dauchet
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur Lille, U1167 - RID-AGE - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, F-59000 Lille, France
| | - Vincent Sobanski
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France; Institut Universitaire de France (IUF), Paris, France.
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8
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Konstantinov KN, Roldan CA, Konstantinov NK. Sclerodactyly, Tongue Telangiectasias, Premature Severe Aortic Stenosis, and RNA Polymerase III Autoantibodies in a Patient with Syncope. Am J Med 2024; 137:e50-e51. [PMID: 37979901 DOI: 10.1016/j.amjmed.2023.10.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 10/16/2023] [Accepted: 10/19/2023] [Indexed: 11/20/2023]
Affiliation(s)
- Konstantin N Konstantinov
- Department of Medicine, Division of Rheumatology, University of New Mexico School of Medicine, Albuquerque; Medicine Service, Rheumatology Section, Raymond G. Murphy Veterans Affairs Medical Center, Albuquerque, NM.
| | - Carlos A Roldan
- Department of Medicine, Division of Cardiology, University of New Mexico School of Medicine, Albuquerque; Medicine Service, Cardiology Section, Raymond G. Murphy Veterans Affairs Medical Center, Albuquerque, NM
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Lazzaroni MG, Piantoni S, Angeli F, Bertocchi S, Franceschini F, Airò P. A Narrative Review of Pathogenetic and Histopathologic Aspects, Epidemiology, Classification Systems, and Disease Outcome Measures in Systemic Sclerosis. Clin Rev Allergy Immunol 2023; 64:358-377. [PMID: 35254622 PMCID: PMC10167186 DOI: 10.1007/s12016-022-08929-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2022] [Indexed: 11/03/2022]
Abstract
Systemic sclerosis (SSc) is a rare systemic autoimmune disease, characterized by the presence of three main actors: vasculopathy, immune activation, and fibrosis. This pathologic process is then translated in a clinical picture with great variability among different patients in terms of type of organ involvement, disease severity and prognosis. This heterogeneity is a main feature of SSc, which, in addition to the presence of early phases of the disease characterized by mild symptoms, can explain the high difficulty in establishing classification criteria, and in defining patients' subsets and disease outcomes. The definition of disease outcomes is particularly relevant in the setting of clinical trials, where the aim is to provide reliable endpoints, able to measure the magnitude of the efficacy of a certain drug or intervention. For this reason, in the last years, increasing efforts have been done to design measures of disease activity, damage, severity, and response to treatment, often in the context of composite indexes. When considering disease outcomes, the experience of the patient represents a relevant and complementary aspect. The tools able to capture this experience, the patient-reported outcomes, have been increasingly used in the last years in clinical practice and in clinical trials, both as primary and secondary endpoints. This comprehensive narrative review on SSc will therefore cover pathogenetic and histopathologic aspects, epidemiology, classification systems, and disease outcome measures, in order to focus on issues that are relevant for clinical research and design of clinical trials.
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Affiliation(s)
- Maria-Grazia Lazzaroni
- Rheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, ASST Spedali Civili of Brescia, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy
| | - Silvia Piantoni
- Rheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, ASST Spedali Civili of Brescia, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy
| | - Fabrizio Angeli
- Rheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, ASST Spedali Civili of Brescia, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy
| | - Stefania Bertocchi
- Rheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, ASST Spedali Civili of Brescia, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy
| | - Franco Franceschini
- Rheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, ASST Spedali Civili of Brescia, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
| | - Paolo Airò
- Rheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, ASST Spedali Civili of Brescia, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy
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10
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Advanced Autoantibody Testing in Systemic Sclerosis. Diagnostics (Basel) 2023; 13:diagnostics13050851. [PMID: 36899995 PMCID: PMC10001109 DOI: 10.3390/diagnostics13050851] [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: 12/13/2022] [Revised: 02/03/2023] [Accepted: 02/06/2023] [Indexed: 02/25/2023] Open
Abstract
Systemic sclerosis is a systemic autoimmune rheumatic disease characterized by immune abnormalities, leading to vasculopathy and fibrosis. Autoantibody testing has become an increasingly important part of diagnosis and prognostication. Clinicians have been limited to antinuclear antibody (ANA), antitopoisomerase I (also known as anti-Scl-70) antibody, and anticentromere antibody testing. Many clinicians now have improved access to an expanded profile of autoantibody testing. In this narrative review article, we review the epidemiology, clinical associations, and prognostic value of advanced autoantibody testing in people with systemic sclerosis.
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11
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Beesley CF, Goldman NR, Taher TE, Denton CP, Abraham DJ, Mageed RA, Ong VH. Dysregulated B cell function and disease pathogenesis in systemic sclerosis. Front Immunol 2023; 13:999008. [PMID: 36726987 PMCID: PMC9885156 DOI: 10.3389/fimmu.2022.999008] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 12/22/2022] [Indexed: 01/18/2023] Open
Abstract
Systemic sclerosis (SSc) is a complex, immune-mediated rheumatic disease characterised by excessive extracellular matrix deposition in the skin and internal organs. B cell infiltration into lesional sites such as the alveolar interstitium and small blood vessels, alongside the production of defined clinically relevant autoantibodies indicates that B cells play a fundamental role in the pathogenesis and development of SSc. This is supported by B cell and fibroblast coculture experiments revealing that B cells directly enhance collagen and extracellular matrix synthesis in fibroblasts. In addition, B cells from SSc patients produce large amounts of profibrotic cytokines such as IL-6 and TGF-β, which interact with other immune and endothelial cells, promoting the profibrotic loop. Furthermore, total B cell counts are increased in SSc patients compared with healthy donors and specific differences can be found in the content of naïve, memory, transitional and regulatory B cell compartments. B cells from SSc patients also show differential expression of activation markers such as CD19 which may shape interactions with other immune mediators such as T follicular helper cells and dendritic cells. The key role of B cells in SSc is further supported by the therapeutic benefit of B cell depletion with rituximab in some patients. It is notable also that B cell signaling is impaired in SSc patients, and this could underpin the failure to induce tolerance in B cells as has been shown in murine models of scleroderma.
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Affiliation(s)
- Claire F. Beesley
- Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom
| | - Nina R. Goldman
- Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom
| | - Taher E. Taher
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Christopher P. Denton
- Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom
| | - David J. Abraham
- Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom
| | - Rizgar A. Mageed
- Centre for Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
| | - Voon H. Ong
- Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom
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12
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Jerjen R, Nikpour M, Krieg T, Denton CP, Saracino AM. Systemic sclerosis in adults. Part I: Clinical features and pathogenesis. J Am Acad Dermatol 2022; 87:937-954. [PMID: 35131402 DOI: 10.1016/j.jaad.2021.10.065] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 10/06/2021] [Accepted: 10/21/2021] [Indexed: 11/27/2022]
Abstract
Systemic sclerosis (SSc), also referred to as systemic scleroderma or scleroderma, is a rare, complex immune-mediated connective tissue disease characterized by progressive skin fibrosis and other clinically heterogenous features. The etiopathogenesis of SSc involves vasculopathy and immune system dysregulation occurring on a permissive genetic and epigenetic background, ultimately leading to fibrosis. Recent developments in our understanding of disease-specific autoantibodies and bioinformatic analyses has led to a reconsideration of the purely clinical classification of diffuse and limited cutaneous SSc subgroups. Autoantibody profiles are predictive of skin and internal organ involvement and disease course. Early diagnosis of SSc, with commencement of disease-modifying treatment, has the potential to improve patient outcomes. In SSc, many of the clinical manifestations that present early signs of disease progression and activity are cutaneous, meaning dermatologists can and should play a key role in the diagnosis and management of this significant condition. The first article in this continuing medical education series discusses the epidemiology, clinical characteristics, and pathogenesis of SSc in adults, with an emphasis on skin manifestations, the important role of dermatologists in recognizing these, and their correlation with systemic features and disease course.
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Affiliation(s)
- Rebekka Jerjen
- Department of Dermatology, The Alfred Hospital, Melbourne, Australia
| | - Mandana Nikpour
- Department of Rheumatology, St Vincent's Hospital, Melbourne, Australia; Department of Medicine, The University of Melbourne, Melbourne, Australia
| | - Thomas Krieg
- Department Dermatology and Translational Matrix Biology, CMMC and CECAD, Faculty of Medicine, University of Cologne, Cologne, Germany
| | - Christopher P Denton
- Division of Medicine, Centre for Rheumatology and Connective Tissues Diseases, University College London, London, United Kingdom; Department of Rheumatology, Royal Free NHS Foundation Trust, London, United Kingdom
| | - Amanda M Saracino
- Department of Dermatology, The Alfred Hospital, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia.
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13
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Ketpueak T, Chanloung W, Nan KN, Pongsananurak C, Kasitanon N, Louthrenoo W. Paclitaxel-induced diffuse scleroderma with possible scleroderma-renal crisis: a case report and literature review of taxanes-induced scleroderma. Clin Rheumatol 2022; 41:3887-3896. [PMID: 36085204 PMCID: PMC9462648 DOI: 10.1007/s10067-022-06364-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 08/31/2022] [Accepted: 09/01/2022] [Indexed: 11/30/2022]
Abstract
Introduction/objectives Scleroderma is a rare complication in taxanes therapy. Although individual cases of taxanes-induced scleroderma have been reported, the clinical manifestation and treatment outcomes were reviewed and summarized rarely. This study reported a patient who developed diffuse scleroderma and possible scleroderma renal crisis after paclitaxel therapy for ureter cancer. Method A PubMed literature review on published cases of taxanes-induced scleroderma up until April 2022 was included for analysis. Results The search identified 27 patients with adequate information for analysis. Of the 28 patients, including the one presented here, 22 were female. Peripheral edema was the most common symptom in all but one patient, and often accompanied by erythema in 11. Symptoms usually occurred in half of the patients within the 4th course of treatment. Skin lesions gradually progressed to skin fibrosis, and extended proximally. Internal organ involvements were uncommon. Antinuclear antibody tests were positive occasionally, but anti-Scl70 and anti-centromere usually were negative. Taxanes therapy was discontinued, continued and unavailable in 21, 3, and 4 patients, respectively. Corticosteroids for skin lesions with or without immunosuppressive drugs were given to 15 patients. Of 25 patients with available skin outcomes, 19 improved. There was no significant skin improvement between those who did or did not receive skin treatment (62.5% vs. 75.0%, p = 0.37). Skin usually improved after discontinuing taxanes. Conclusion Taxanes-induced scleroderma is different from idiopathic scleroderma. Physicians should be aware of this condition in order to provide early diagnosis and apply appropriate management in order to avoid serious complications from severe skin sclerosis.
| Key Points | • Scleroderma is a rare but unique and serious complication of taxanes therapy • Skin manifestations and distribution are similar to idiopathic scleroderma, but vascular phenomenon, internal organ involvement and scleroderma-associated auto-antibodies are presented rarely. Skin improvement usually occurs shortly after discontinuing taxanes • The role of immunosuppressive therapy in treating taxanes-induced scleroderma is not clear |
Supplementary Information The online version contains supplementary material available at 10.1007/s10067-022-06364-z.
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Affiliation(s)
- Thanika Ketpueak
- Division of Oncology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, 50200, Chiang Mai, Thailand
| | - Wanitcha Chanloung
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, 50200, Chiang Mai, Thailand
| | - Kittiya Na Nan
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, 50200, Chiang Mai, Thailand
| | | | - Nuntana Kasitanon
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, 50200, Chiang Mai, Thailand
| | - Worawit Louthrenoo
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, 50200, Chiang Mai, Thailand.
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14
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Maritati F, Provenzano M, Lerario S, Corradetti V, Bini C, Busutti M, Grandinetti V, Cuna V, La Manna G, Comai G. Kidney transplantation in systemic sclerosis: Advances in graft, disease, and patient outcome. Front Immunol 2022; 13:878736. [PMID: 35958558 PMCID: PMC9360313 DOI: 10.3389/fimmu.2022.878736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 06/30/2022] [Indexed: 11/30/2022] Open
Abstract
Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis, and inflammation. Renal disease occurring in patients with SSc may have a variable clinicopathological picture. However, the most specific renal condition associated with this disease is the scleroderma renal crisis (SRC), characterized by acute onset of renal failure and severe hypertension. SRC develops in about 20% of cases of SSc, especially in those patients with diffuse cutaneous disease. The prognosis of this condition is often negative, with a rapid progression to end-stage renal disease (ESRD). The advent of the antihypertensive angiotensin-converting enzyme inhibitors in 1980 was associated with a significant improvement in patients’ survival and recovery of renal function. However, the prognosis of these patients can still be improved. The dialytic condition is associated with early death, and mortality is significantly higher than among patients undergoing renal replacement therapy (RRT) due to other conditions. Patients with SRC who show no signs of renal functional recovery despite timely blood pressure control are candidates for kidney transplantation (KT). In this review, we reported the most recent advances in KT in patients with ESRD due to SSc, with a particular overview of the risk of disease recurrence after transplantation and the evolution of other disease manifestations.
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15
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Chepy A, Bourel L, Koether V, Launay D, Dubucquoi S, Sobanski V. Can Antinuclear Antibodies Have a Pathogenic Role in Systemic Sclerosis? Front Immunol 2022; 13:930970. [PMID: 35837382 PMCID: PMC9274282 DOI: 10.3389/fimmu.2022.930970] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 05/26/2022] [Indexed: 12/30/2022] Open
Abstract
Systemic sclerosis (SSc) is a connective tissue disease characterized by extensive fibrosis of the skin and internal organs, associated with vasculopathy and autoimmune features. Antinuclear antibodies (ANA) are found in almost all SSc patients and constitute strong diagnosis and prognosis biomarkers. However, it remains unclear whether ANA are simple bystanders or if they can have a role in the pathophysiology of the disease. One might think that the nuclear nature of their targets prevents any accessibility to autoantibodies. Nevertheless, recent data suggest that ANA could be pathogenic or at least contribute to the perennation of the disease. We review here first the indirect clues of the contribution of ANA to SSc: they are associated to the disease subtypes, they may precede disease onset, their titer correlates with disease activity and severity, there is an association between molecular subsets, and some patients can respond to B-cell targeting therapy. Then, we describe in a second part the mechanisms of ANA production in SSc from individual genetic background to post-transcriptional modifications of neoantigens. Finally, we elaborate on the potential mechanisms of pathogenicity: ANA could be pathogenic through immune-complex-mediated mechanisms; other processes potentially involve molecular mimicry and ANA penetration into the target cell, with a focus on anti-topoisomerase-I antibodies, which are the most probable candidate to play a role in the pathophysiology of SSc. Finally, we outline some technical and conceptual ways to improve our understanding in this field.
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Affiliation(s)
- Aurélien Chepy
- Univ. Lille, Inserm, CHU Lille, U1286—INFINITE—Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Lille, France
| | - Louisa Bourel
- Univ. Lille, Inserm, CHU Lille, U1286—INFINITE—Institute for Translational Research in Inflammation, Lille, France
| | - Vincent Koether
- Univ. Lille, Inserm, CHU Lille, U1286—INFINITE—Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Lille, France
| | - David Launay
- Univ. Lille, Inserm, CHU Lille, U1286—INFINITE—Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Lille, France
| | - Sylvain Dubucquoi
- Univ. Lille, Inserm, CHU Lille, U1286—INFINITE—Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Institut d’Immunologie, Lille, France
| | - Vincent Sobanski
- Univ. Lille, Inserm, CHU Lille, U1286—INFINITE—Institute for Translational Research in Inflammation, Lille, France
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Lille, France
- Institut Universitaire de France (IUF), Paris, France
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16
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Cavazzana I, Vojinovic T, Airo' P, Fredi M, Ceribelli A, Pedretti E, Lazzaroni MG, Garrafa E, Franceschini F. Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers. Clin Rev Allergy Immunol 2022; 64:412-430. [PMID: 35716254 PMCID: PMC10167150 DOI: 10.1007/s12016-022-08946-w] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/18/2021] [Indexed: 11/28/2022]
Abstract
Disease-specific autoantibodies are considered the most important biomarkers for systemic sclerosis (SSc), due to their ability to stratify patients with different severity and prognosis. Anti-nuclear antibodies (ANA), occurring in subjects with isolated Raynuad's phenomenon, are considered the strongest independent predictors of definite SSc and digital microvascular damage, as observed by nailfold videocapillaroscopy. ANA are present in more than 90% of SSc, but ANA negativity does not exclude SSc diagnosis: a little rate of SSc ANA negative exists and shows a distinct subtype of disease, with less vasculopathy, but more frequent lower gastrointestinal involvement and severe disease course. Anti-centromere, anti-Th/To, and anti-Topoisomerase I antibodies could be considered as classical biomarkers, covering about 60% of SSc and defining patients with well-described cardio-pulmonary complications. In particular, anti-Topoisomerase I represent a risk factor for development of diffuse cutaneous involvement and digital ulcers in the first 3 years of disease, as well as severe interstitial lung disease (ILD). Anti-RNA polymerase III is a biomarker with new clinical implications: very rapid skin thickness progression, gastric antral vascular ectasia, the occurrence of synchronous cancers, and possible association with silicone breast implants rupture. Moreover, novel SSc specific autoantibodies have been globally described in about 10% of "seronegative" SSc patients: anti-elF2B, anti-RuvBL1/2 complex, anti-U11/U12 RNP, and anti-BICD2 depict specific SSc subtypes with severe organ complications. Many autoantibodies could be considered markers of overlap syndromes, including SSc. Anti-Ku are found in 2-7% of SSc, strictly defining the PM/SSc overlap. They are associated with synovitis, joint contractures, myositis, and negatively associated with vascular manifestation of disease. Anti-U3RNP are associated with a well-defined clinical phenotype: Afro-Caribbean male patients, younger at diagnosis, and higher risk of pulmonary hypertension and gastrointestinal involvement. Anti-PM/Scl define SSc patients with high frequency of ILD, calcinosis, dermatomyositis skin changes, and severe myositis. The accurate detection of autoantibodies SSc specific and associated with overlap syndromes is crucial for patients' stratification. ANA should be correctly identified using indirect immunofluorescent assay and a standardized way of patterns' interpretation. The gold-standard technique for autoantibodies' identification in SSc is still considered immunoprecipitation, for its high sensitivity and specificity, but other assays have been widely used in routine practice. The identification of SSc autoantibodies with high diagnostic specificity and high predictive value is mandatory for early diagnosis, a specific follow-up and the possible definition of the best therapy for every SSc subsets. In addition, the validation of novel autoantibodies is mandatory in wider cohorts in order to restrict the gap of so-called seronegative SSc patients.
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Affiliation(s)
- Ilaria Cavazzana
- Rheumatology and Clinical Immunology Unit, ASST Spedali Civili, piazzale Spedali Civili 1, Brescia, 25123, Italy.
| | - Tamara Vojinovic
- Rheumatology and Clinical Immunology Unit, ASST Spedali Civili, piazzale Spedali Civili 1, Brescia, 25123, Italy
| | - Paolo Airo'
- Rheumatology and Clinical Immunology Unit, ASST Spedali Civili, piazzale Spedali Civili 1, Brescia, 25123, Italy
| | - Micaela Fredi
- Rheumatology and Clinical Immunology Unit, ASST Spedali Civili, piazzale Spedali Civili 1, Brescia, 25123, Italy.,Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Angela Ceribelli
- Division of Rheumatology and Clinical Immunology, Humanitas Research Hospital IRCCS, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Eleonora Pedretti
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Maria Grazia Lazzaroni
- Rheumatology and Clinical Immunology Unit, ASST Spedali Civili, piazzale Spedali Civili 1, Brescia, 25123, Italy.,Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Emirena Garrafa
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.,Department of Laboratory Diagnostics, ASST Spedali Civili, Brescia, Italy
| | - Franco Franceschini
- Rheumatology and Clinical Immunology Unit, ASST Spedali Civili, piazzale Spedali Civili 1, Brescia, 25123, Italy.,Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
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17
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Cole A, Ong VH, Denton CP. Renal Disease and Systemic Sclerosis: an Update on Scleroderma Renal Crisis. Clin Rev Allergy Immunol 2022; 64:378-391. [PMID: 35648373 PMCID: PMC10167155 DOI: 10.1007/s12016-022-08945-x] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/11/2022] [Indexed: 12/16/2022]
Abstract
Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality in scleroderma (SSc), it remains a serious complication, often necessitating level three care for patients affected. Whilst renal outcomes have significantly improved following the advent of angiotensin-converting enzyme inhibitor (ACEi) therapy, SRC remains a precarious challenge for clinicians, due to lack of preventative measures and the fact that patients can rapidly decline despite best medical management. Large cohort studies spanning decades have allowed clear identification of phenotypes particularly at risk of developing SRC thus allowing enhanced monitoring and early identification in those individuals. Novel urinary biomarkers for renal disease in SSc may offer a new window for early identification of SRC patients and response to treatment. Multiple studies have demonstrated increased activity of complement pathways in SRC with some anecdotal cases exhibiting serological response to treatment with eculizumab where ACEi and therapeutic plasma exchange (TPE) were not successful. Endothelin-1 blockade, a therapeutic strategy in other SSc vasculopathies, has shown potential as a target but clinical trials are yet to show a clear treatment benefit. Clear guidelines for the management of SRC are in place to standardise care and facilitate early collaboration between rheumatology and renal physicians. Outcomes following renal transplant have improved but the mortality of SRC remains high, indicating the need for continued exploration of the mechanisms precipitating and exacerbating SRC in order to develop novel therapies.
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Affiliation(s)
- Alice Cole
- UCL Centre for Rheumatology and Connective Tissue Diseases, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK
| | - Voon H Ong
- UCL Centre for Rheumatology and Connective Tissue Diseases, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK
| | - Christopher P Denton
- UCL Centre for Rheumatology and Connective Tissue Diseases, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK.
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18
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Capillaroscopy and Immunological Profile in Systemic Sclerosis. Life (Basel) 2022; 12:life12040498. [PMID: 35454989 PMCID: PMC9024594 DOI: 10.3390/life12040498] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/15/2022] [Accepted: 03/26/2022] [Indexed: 11/22/2022] Open
Abstract
Introduction: Data on the associations between capillaroscopic changes and diagnostic systemic-sclerosis (SSc)-related antibodies are scarce. Presence of such correlation would improve current knowledge about the disease’s pathogenesis by revealing the mechanisms of microangiopathy. The microvascular pathology of SSc is a hallmark of the disease, and immunological abnormalities probably contribute to its development. Patients and methods: 19 patients with definite diagnosis of SSc were included in the current pilot study; 16 had limited and 3 had diffuse cutaneous involvement; their mean age was 51.56 ± 15.07 years. All patients exhibited symptoms of Raynaud’s phenomenon of the fingers. A “scleroderma” type capillaroscopic pattern was classified according to the staging suggested by Cutolo et al. (2000): “early”, “active” or ”late” phase. In the presence of different degrees of capillaroscopic changes in different fingers, the most-advanced microvascular pathology was chosen for classification. In cases without capillaroscopic features of microangiopathy, the findings were categorized as normal or nonspecific (dilated, tortuous capillaries, and/or hemorrhages). Indirect immunofluorescence on HEp-2 cells was performed as the gold-standard screening method for the detection of antinuclear autoantibodies (ANA), and determination of the immunofluorescent staining pattern (anti-cell pattern) was in accordance with the International Consensus on ANA Patterns. Scleroderma-associated autoantibodies in the patients’ serum were assessed using line immunoblot assay for detection of autoantibodies to 13 scleroderma-associated autoantigens: Scl-70, CENP A, CENP B, RP11/RNAP-III, RP155/RNAP-III, fibrillarin, NOR-90, Th/To, PM-Scl100, PM-Scl75, Ku, PDGFR, and Ro-52. Results: In 73.7% (n = 14) of the examined patients, “scleroderma” type capillaroscopic changes were found, and in 26.3% (n = 5), capillaroscopic features of microangiopathy were absent (nonspecific changes, n = 3; normal findings, n = 2). In SSc patients with positive anti-Scl-70 (n = 7) antibodies, significantly lower mean capillary density was observed along with a higher frequency of “active” and “late” phase capillaroscopic changes as compared to the anti-Scl-70-negative patients (p < 0.05). Anti-RNAP III−155 positive patients (n = 4) had significantly higher mean capillary density than anti-RNAP III−155 negative patients (n = 15). In three of the anti-RNAP III−155-positive cases, capillaroscopic features of microangiopathy were not detected, and in one case there was an “early” phase “scleroderma” pattern. Conclusion: In the current pilot study, the association between more advanced capillaroscopic changes and the presence of anti-Scl-70 autoantibodies was confirmed. As a novel observation, positive anti-RNAP III−155 antibodies were found in SSc patients with or without early microangiopathy. The question of associations between microvascular changes in SSc and other SSc-related autoantibodies requires further research.
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19
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Damoiseaux J, Potjewijd J, Smeets RL, Bonroy C. Autoantibodies in the disease criteria for systemic sclerosis: The need for specification for optimal application. J Transl Autoimmun 2022; 5:100141. [PMID: 35028553 PMCID: PMC8741499 DOI: 10.1016/j.jtauto.2022.100141] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 01/02/2022] [Indexed: 01/03/2023] Open
Abstract
The ACR/EULAR classification criteria for systemic sclerosis (SSc) entail three autoantibodies: anti-centromere antibodies (ACA), anti-topoisomerase I antibodies (ATA), and anti-RNA-polymerase III antibodies (ARA). The importance of ACA and ATA in the classification criteria is evidence based, but the diagnostic value is overestimated by clinicians. Fortunately, these autoantibodies are characterized by good agreement between different immuno-assays. Inclusion of ARA, however, is based on limited evidence and is related to limited agreement between different immuno-assays. Harmonization of immuno-assays in terms of interpretation based on likelihood ratio's may improve future classification criteria for SSc and this needs to be achieved by close collaboration between clinicians, laboratory specialists and the diagnostic industry.
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Affiliation(s)
- Jan Damoiseaux
- Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Judith Potjewijd
- Department of Internal Medicine, Division Nephrology and Clinical Immunology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Ruben L. Smeets
- Department of Laboratory Medicine, Radboudumc Laboratory for Diagnostics, Radboud University Medical Center, Nijmegen, the Netherlands
- Department of Laboratory Medicine—Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Carolien Bonroy
- Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
- Department of Diagnostic Sciences, Ghent University, Ghent, Belgium
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20
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Abbas F, El Kossi M, Shaheen IS, Sharma A, Halawa A. Journey of a patient with scleroderma from renal failure up to kidney transplantation. World J Transplant 2021; 11:372-387. [PMID: 34631469 PMCID: PMC8465513 DOI: 10.5500/wjt.v11.i9.372] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/10/2021] [Accepted: 08/19/2021] [Indexed: 02/06/2023] Open
Abstract
The increased awareness of systemic sclerosis (SS) and its pathogenetic background made the management of this disease more amenable than previously thought. However, scleroderma renal crisis (SRC) is a rarely seen as an associated disorder that may involve 2%-15% of SS patients. Patients presented with earlier, rapidly progressing, diffuse cutaneous SS disease, mostly in the first 3-5 years after non-Raynaud clinical manifestations, are more vulnerable to develop SRC. SRC comprises a collection of acute, mostly symptomatic rise in blood pressure, elevation in serum creatinine concentrations, oliguria and thrombotic microangiopathy in almost 50% of cases. The advent of the antihypertensive angiotensin converting enzyme inhibitors in 1980 was associated with significant improvement in SRC prognosis. In a scleroderma patient maintained on regular dialysis; every effort should be exerted to declare any possible evidence of renal recovery. A given period of almost two years has been suggested prior to proceeding in a kidney transplant (KTx). Of note, SS patients on dialysis have the highest opportunity of renal recovery and withdrawal from dialysis as compared to other causes of end-stage renal disease (ESRD). KTx that is the best well-known therapeutic option for ESRD patients can also be offered to SS patients. Compared to other primary renal diseases, SS-related ESRD was considered for a long period of poor patient and allograft survivals. Pulmonary involvement in an SS patient is considered a strong post-transplant independent risk factor of death. Recurrence of SRC after transplantation has been observed in some patients. However, an excellent post-transplant patient and graft outcome have been recently reported. Consequently, the absence of extrarenal manifestations in an SS-induced ESRD patient can be accepted as a robust indicator for a successful KTx.
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Affiliation(s)
- Fedaey Abbas
- Department of Nephrology, Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
| | - Mohsen El Kossi
- Doncaster Renal Unit, Doncaster Royal Infirmary, Doncaster DN2 5LT, United Kingdom
| | - Ihab Sakr Shaheen
- Department of Paediatric Nephrology, St James’s University Hospital, Glasgow G51 4TF, United Kingdom
| | - Ajay Sharma
- Department of Transplant Surgery, Royal Liverpool University Hospital, Liverpool L7 8XP, United Kingdom
| | - Ahmed Halawa
- Department of Transplant Surgery, Sheffield Teaching Hospital, Sheffield S5 7AU, United Kingdom
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21
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Gargiulo MDLÁ, Perez N, Khoury M, Buhl M, Suárez L, Sarano J, Montoya F, Bazzalo I, Navarro S, Pendón G, Molina MJ, Mamani M, Rivero M, Gómez G. Anti-RNA polymerase III antibodies in systemic sclerosis: Multicentric study from Argentina. ACTA ACUST UNITED AC 2021; 18:368-373. [PMID: 34366290 DOI: 10.1016/j.reumae.2021.02.003] [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: 03/12/2020] [Accepted: 02/11/2021] [Indexed: 11/16/2022]
Abstract
OBJECTIVE To describe the frequency of anti-RNA polymerase III antibody in patients with Systemic Sclerosis (SSc) of a group of healthcare centres from Argentina and to explore differences among patients with positive and negative anti-RNA polymerase III antibody. PATIENTS AND METHODS Data from clinical records, anamnesis and physical examination were collected from 135 patients with SSc (ACR/EULAR 2013). A serum sample from each patient was obtained for the detection of anti-RNA polymerase III IgG antibodies by ELISA. RESULTS In all, 97.8% were women and the median age at diagnosis was 53 years (range 12-87), 77.7% had limited cutaneous SSc (lcSSC), 19,3% patients had diffuse cutaneous SSc (dcSSC) and 2.9% had scleroderma sine scleroderma. The 67.5% of the patients were from a Mestizos or Amerindian ethnic group. Anti-RNA polymerase III was positive in 5.9% of the patients. In 36 patients, the anticentromere (ACA) and anti-Scl70 antibodies were negative; anti-RNA polymerase III was positive in 16.7% of these 36 patients. Pitting scars and pulmonary artery hypertension were more frequent in anti-RNA polymerase III positive patients who were also older at diagnosis. No association with gastric antral vascular ectasia was found. The only patient with scleroderma renal crisis was anti-RNA polymerase III positive. CONCLUSIONS Anti-RNA polymerase III frequency found in this study was one of the lowest reported, which could be related to the predominance of the Amerindian and Mestizo ethnic group. It is possible that the detection of anti RNA polymerase III allows better classification of SSc patients, to know their prognosis and to improve their follow-up, therefore more studies are needed.
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Affiliation(s)
- María de Los Ángeles Gargiulo
- Servicio de Inmunología, Instituto de Investigaciones Médicas "Dr. Alfredo Lanari", UBA, Ciudad Autónoma de Buenos Aires, Argentina.
| | - Nicolás Perez
- Servicio de Inmunología, Instituto de Investigaciones Médicas "Dr. Alfredo Lanari", UBA, Ciudad Autónoma de Buenos Aires, Argentina
| | - Marina Khoury
- Docencia e Investigación, Instituto de Investigaciones Médicas "Dr. Alfredo Lanari", UBA, Ciudad Autónoma de Buenos Aires, Argentina
| | - Manuel Buhl
- Servicio de Inmunología, Instituto de Investigaciones Médicas "Dr. Alfredo Lanari", UBA, Ciudad Autónoma de Buenos Aires, Argentina
| | - Lorena Suárez
- Servicio de Inmunología, Instituto de Investigaciones Médicas "Dr. Alfredo Lanari", UBA, Ciudad Autónoma de Buenos Aires, Argentina
| | - Judith Sarano
- Servicio de Inmunología, Instituto de Investigaciones Médicas "Dr. Alfredo Lanari", UBA, Ciudad Autónoma de Buenos Aires, Argentina
| | - Fabiana Montoya
- Servicio de Reumatología y Colagenopatías, Hospital General de Agudos José María Ramos Mejía, Ciudad Autónoma de Buenos Aires, Argentina
| | - Ignacio Bazzalo
- Servicio de Reumatología y Colagenopatías, Hospital General de Agudos José María Ramos Mejía, Ciudad Autónoma de Buenos Aires, Argentina
| | - Sandra Navarro
- Servicio de Reumatología, Hospital Provincial del Centenario, Rosario, Santa Fe, Argentina
| | - Gisela Pendón
- Unidad de Reumatología, Hospital "Dr. Ricardo Gutiérrez", La Plata, Buenos Aires, Argentina
| | - María Josefina Molina
- Consultorio de Reumatología, Hospital Central de San Isidro "Dr. Melchor A Posse", San Isidro, Buenos Aires, Argentina
| | - Marta Mamani
- Servicio de Reumatología, Hospital General de Agudos Bernardino Rivadavia, Ciudad Autónoma de Buenos Aires. Argentina
| | - Mariano Rivero
- Servicio de Reumatología, Hospital Británico de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
| | - Graciela Gómez
- Servicio de Inmunología, Instituto de Investigaciones Médicas "Dr. Alfredo Lanari", UBA, Ciudad Autónoma de Buenos Aires, Argentina
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22
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Gargiulo MDLÁ, Pérez N, Khoury M, Buhl M, Suárez L, Sarano J, Montoya F, Bazzalo I, Navarro S, Pendón G, Molina MJ, Mamani M, Rivero M, Gómez G. Anti-RNA Polymerase III Antibodies in Systemic Sclerosis: Multicentric Study from Argentina. REUMATOLOGIA CLINICA 2021; 18:S1699-258X(21)00059-0. [PMID: 33933370 DOI: 10.1016/j.reuma.2021.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 01/31/2021] [Accepted: 02/11/2021] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To describe the frequency of anti-RNA polymerase III antibody in patients with Systemic Sclerosis (SSc) of a group of healthcare centres from Argentina and to explore differences among patients with positive and negative anti-RNA polymerase III antibody. PATIENTS AND METHODS Data from clinical records, anamnesis and physical examination were collected from 135 patients with SSc (ACR/EULAR 2013). A serum sample from each patient was obtained for the detection of anti-RNA polymerase III IgG antibodies by ELISA. RESULTS In all, 97.8% were women and the median age at diagnosis was 53 years (range: 12-87), 77.7% had limited cutaneous SSc (lcSSC), 19,3% patients had diffuse cutaneous SSc (dcSSC) and 2.9% had scleroderma sine scleroderma. The 67.5% of the patients were from a Mestizos or Amerindian ethnic group. Anti-RNA polymerase III was positive in 5.9% of the patients. In 36 patients, the anticentromere (ACA) and anti-Scl70 antibodies were negative; anti-RNA polymerase III was positive in 16.7% of these 36 patients. Pitting scars and pulmonary artery hypertension were more frequent in anti-RNA polymerase III positive patients who were also older at diagnosis. No association with gastric antral vascular ectasia was found. The only patient with scleroderma renal crisis was anti-RNA polymerase III positive. CONCLUSIONS Anti-RNA polymerase III frequency found in this study was one of the lowest reported, which could be related to the predominance of the Amerindian and Mestizo ethnic group. It is possible that the detection of anti-RNA polymerase III allows better classification of SSc patients, to know their prognosis and to improve their follow-up, therefore more studies are needed.
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Affiliation(s)
- María de Los Ángeles Gargiulo
- Servicio de Inmunología, Instituto de Investigaciones Médicas «Dr. Alfredo Lanari», UBA, Ciudad Autónoma de Buenos Aires, Argentina.
| | - Nicolás Pérez
- Servicio de Inmunología, Instituto de Investigaciones Médicas «Dr. Alfredo Lanari», UBA, Ciudad Autónoma de Buenos Aires, Argentina
| | - Marina Khoury
- Docencia e Investigación, Instituto de Investigaciones Médicas «Dr. Alfredo Lanari», UBA, Ciudad Autónoma de Buenos Aires, Argentina
| | - Manuel Buhl
- Servicio de Inmunología, Instituto de Investigaciones Médicas «Dr. Alfredo Lanari», UBA, Ciudad Autónoma de Buenos Aires, Argentina
| | - Lorena Suárez
- Servicio de Inmunología, Instituto de Investigaciones Médicas «Dr. Alfredo Lanari», UBA, Ciudad Autónoma de Buenos Aires, Argentina
| | - Judith Sarano
- Servicio de Inmunología, Instituto de Investigaciones Médicas «Dr. Alfredo Lanari», UBA, Ciudad Autónoma de Buenos Aires, Argentina
| | - Fabiana Montoya
- Servicio de Reumatología y Colagenopatías, Hospital General de Agudos José María Ramos Mejía, Ciudad Autónoma de Buenos Aires, Argentina
| | - Ignacio Bazzalo
- Servicio de Reumatología y Colagenopatías, Hospital General de Agudos José María Ramos Mejía, Ciudad Autónoma de Buenos Aires, Argentina
| | - Sandra Navarro
- Servicio de Reumatología, Hospital Provincial del Centenario, Rosario, Santa Fe, Argentina
| | - Gisela Pendón
- Unidad de Reumatología, Hospital «Dr. Ricardo Gutiérrez», La Plata, Buenos Aires, Argentina
| | - María Josefina Molina
- Consultorio de Reumatología, Hospital Central de San Isidro «Dr. Melchor A Posse», San Isidro, Buenos Aires, Argentina
| | - Marta Mamani
- Servicio de Reumatología, Hospital General de Agudos Bernardino Rivadavia, Ciudad Autónoma de Buenos Aires, Argentina
| | - Mariano Rivero
- Servicio de Reumatología, Hospital Británico de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
| | - Graciela Gómez
- Servicio de Inmunología, Instituto de Investigaciones Médicas «Dr. Alfredo Lanari», UBA, Ciudad Autónoma de Buenos Aires, Argentina
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23
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Hudson M, Ghossein C, Steen V. Scleroderma renal crisis. Presse Med 2021; 50:104063. [PMID: 33548376 DOI: 10.1016/j.lpm.2021.104063] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 10/27/2020] [Indexed: 01/17/2023] Open
Abstract
Scleroderma renal crisis (SRC) is a rare but life-threatening complication of systemic sclerosis (SSc) characterized by malignant hypertension and acute kidney injury. Historically, SRC was the leading cause of death in SSc. However, with the advent of angiotensin converting enzyme (ACE) inhibitors, mortality rates have decreased significantly. Nevertheless, one-year outcomes remain poor, with over 30% mortality and 25% of patients remaining dialysis-dependent. There is an urgent need to improve early recognition and treatment, and to identify novel treatments to improve outcomes of SRC. In this chapter, the clinical features, classification, pathophysiology, differential diagnosis, management and outcomes of SRC are presented. Specific issues relating to pregnancy, prophylactic ACE inhibition and management of essential hypertension are also discussed.
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Affiliation(s)
- Marie Hudson
- Jewish General Hospital, Lady Davis Institute, McGill University, Montreal, Canada
| | - Cybele Ghossein
- Feinberg School of Medicine, Northwestern University, Chicago, USA
| | - Virginia Steen
- Georgetown University Medical Center, Washington (DC), USA
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24
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Alhendi FJ, Werth VP, Sollecito TP, Stoopler ET. Systemic sclerosis: Update for oral health care providers. SPECIAL CARE IN DENTISTRY 2021; 40:418-430. [PMID: 33448431 DOI: 10.1111/scd.12492] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 06/05/2020] [Accepted: 06/09/2020] [Indexed: 12/22/2022]
Abstract
Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disease of unknown origin characterized by an uncontrolled inflammatory process resulting in fibrosis of the skin, internal organs and vasculopathy. Manifestations of SSc are heterogenous and can include pulmonary, cardiac, neural, renal, muscular, cutaneous and orofacial complications. Recent scientific advances have led to a better understanding of disease etiopathogenesis and the development of a new classification system. Therapeutic management is often multidisciplinary and targeted toward the affected organs. Oral health care providers (OHCPs) should be familiar with SSc, particularly as it relates to its impact on the orofacial region and modifications to delivery of oral health care for patients with this condition.
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Affiliation(s)
- Fatmah J Alhendi
- Department of Oral Medicine, Penn Dental Medicine, Philadelphia, Pennsylvania
| | - Victoria P Werth
- Department of Dermatology, Philadelphia V.A. Hospital, Hospital of the University of Pennsylvania and the Veteran's Administration Medical Center, Philadelphia, Pennsylvania
| | - Thomas P Sollecito
- Department of Oral Medicine, Penn Dental Medicine, Philadelphia, Pennsylvania
| | - Eric T Stoopler
- Department of Oral Medicine, Penn Dental Medicine, Philadelphia, Pennsylvania
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25
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Clinical consequences of the presence of anti-RNA Pol III antibodies in systemic sclerosis. Postepy Dermatol Alergol 2021; 37:909-914. [PMID: 33603608 PMCID: PMC7874867 DOI: 10.5114/ada.2020.102107] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 04/26/2019] [Indexed: 01/25/2023] Open
Abstract
Introduction Anti-RNA polymerase III (a-RNA Pol III) antibodies are marker antibodies in patients with systemic sclerosis (SSc). Aim To assess the prevalence of a-RNA Pol III in patients with SSc and to identify the differences in the disease picture in SSc patients with and without a-RNA Pol III antibodies. Material and methods The study was performed in 126 SSc patients. The subtype of SSc, incidence of internal organ involvement, malignancy, death and serological profiles were determined in the entire group. The study groups were studied according to the presence of antibodies by applying the commercial test - EUROLINE SSc Profile. Due to the presence of a-RNA Pol III, patients were divided into two groups: the a-RNA Pol III (+) SSc group of 19 patients and the a-RNA Pol III (-) SSc group of 107 patients. Results A-RNA Pol III were present in 19/126 patients with SSc (15%), 13/19 (68.4%) patients had no other SSc marker antibodies. A-RNA Pol III were more common in patients with diffuse cutaneous SSc (p = 0.049). We showed a significant positive association between a-RNA Pol III and occurrence of malignancy (p = 0.007), scleroderma renal crisis (p = 0.001) and decreased DLCO (p = 0.007). Conclusions Anti-a-RNA Pol III antibodies are common in patients with SSc, particularly with a diffuse subtype. In more than 50% of patients with a-RNA Pol III antibodies, they may be present as the sole marker of antibodies. In SSc, a-RNA Pol III antibodies are frequently associated with malignancy occurrence, kidney and lung involvement.
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26
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Stochmal A, Czuwara J, Trojanowska M, Rudnicka L. Antinuclear Antibodies in Systemic Sclerosis: an Update. Clin Rev Allergy Immunol 2020; 58:40-51. [PMID: 30607749 DOI: 10.1007/s12016-018-8718-8] [Citation(s) in RCA: 102] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Systemic sclerosis is an autoimmune disease characterized by fibrosis of skin and internal organs, vasculopathy, and dysregulation of immune system. A diagnostically important feature of immunological abnormalities in systemic sclerosis is the presence of circulating antinuclear antibodies, which may be detected in 90-95% of patients with either of the four main laboratory methods: immunofluorescence, enzyme-linked immunosorbent assay, immunodiffusion, and immunoblotting. There are several antinuclear antibodies specific for systemic sclerosis. These include antibodies against topoisomerase (anti-TOPO I), kinetochore proteins (ACA), RNA polymerase enzyme (anti-RNAP III), ribonuclear proteins (anti-U11/U12 RNP, anti-U1 RNP, anti-U3 RNP) and nucleolar antigens (anti-Th/To, anti-NOR 90, anti-Ku, antiRuvBL1/2, and anti-PM/Scl). Autoantibodies specific for systemic sclerosis have been linked to distinct clinical features. Therefore, detecting a particular antibody type is important in predicting a possible organ involvement and prognosis and may have an impact on monitoring and treatment.
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Affiliation(s)
- Anna Stochmal
- Department of Dermatology, Medical University of Warsaw, Koszykowa 82A, 02-008, Warsaw, Poland
| | - Joanna Czuwara
- Department of Dermatology, Medical University of Warsaw, Koszykowa 82A, 02-008, Warsaw, Poland
| | - Maria Trojanowska
- Arthritis Center, Boston University School of Medicine, Boston, MA, USA
| | - Lidia Rudnicka
- Department of Dermatology, Medical University of Warsaw, Koszykowa 82A, 02-008, Warsaw, Poland.
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27
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Qin Y, Huang X, Chen H, Liu X, Li Y, Hou J, Li A, Yan X, Chen Y. Burden of Talaromyces marneffei infection in people living with HIV/AIDS in Asia during ART era: a systematic review and meta-analysis. BMC Infect Dis 2020; 20:551. [PMID: 32727383 PMCID: PMC7392840 DOI: 10.1186/s12879-020-05260-8] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 07/16/2020] [Indexed: 12/11/2022] Open
Abstract
Background Talaromyces marneffei (TM) is a dimorphic fungus mainly prevalent in Southeast Asian countries, which often causes disseminated life-threatening infection. TM infection often occurs in HIV/AIDS patients even in the antiretroviral therapy (ART) era. However, there has as yet, not been a systematic analysis of the prevalence of TM infection in HIV-infected populations in Asia. Methods In this study, we searched Pubmed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang from inception to 21 November 2018 for studies reporting TM infection in people living with HIV/AIDS (PLWHA). Our meta-analysis included studies investigating the prevalence of TM infection in PLWHA. Reviews, duplicate studies, and animal studies were excluded. A random effects model was used to estimate pooled prevalence, and meta-regression analysis was conducted to explore potential factors for heterogeneity. Results 159,064 patients with HIV infection in 33 eligible studies were included in our meta-analysis. The pooled prevalence of TM infection in PLWHA was 3.6%. Vietnam had the highest prevalence (6.4%), followed by Thailand (3.9%), China (3.3%), India (3.2%) and Malaysia (2.1%). In China, TM infection was most prevalent in South China (15.0%), while the burden in Southwest China was not very heavy (0.3%). CD4+ T-cell counts below 200 cells/mm3 contributed to the increased risk of TM infection in PLWHA (OR 12.68, 95%CI: 9.58–16.77). However, access to ART did not significantly decrease the risk of TM infection in PLWHA. Conclusions The burden of TM infection in Asia is heavy, and varies from region to region. PLWHA in lower latitude areas are more likely to suffer from TM infection. Optimization of diagnostic tools and universal screening for TM in vulnerable people to ensure early case detection and prompt antifungal treatment should be considered.
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Affiliation(s)
- Yuanyuan Qin
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China.,Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xiaojie Huang
- Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Hui Chen
- School of Biomedical Engineering, Capital Medical University, Beijing, China
| | - Xinchao Liu
- Infectious Diseases Department, Peking Union Medical College Hospital, Beijing, China
| | - Yao Li
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China.,Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jianhua Hou
- Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Aixin Li
- Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xiaofeng Yan
- Chongqing Public Health Medical Center, Chongqing, China.
| | - Yaokai Chen
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China.
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28
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Taieb D, Chauveau S, Khamis W, de Montmollin N, Sesé L, Duchemann B, Nunes H, Uzunhan Y. [A case of systemic sclerosis]. Rev Mal Respir 2020; 37:341-345. [PMID: 32284205 DOI: 10.1016/j.rmr.2020.02.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 02/07/2020] [Indexed: 11/19/2022]
Abstract
In systemic sclerosis, the presence of an anti-RNA polymerase III antibody (ARNpol3) is associated with an increased risk of cancer. The characteristic picture of this serotype includes severe diffuse cutaneous involvement, a high risk of renal scleroderma crisis and a 10 year survival of only around 30%. Pulmonary involvement is less common. We report the case of a woman initially treated for drug-induced acute interstitial lung disease revealing chronic interstitial pneumonia with autoimmune features. The disease evolved in three stages with the occurrence of a rapidly progressive diffuse skin sclerosis with anti-ARNPol3 antibodies in the context of ovarian cancer remission.
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Affiliation(s)
- D Taieb
- Service de pneumologie, hôpital Avicenne, centre de référence des maladies pulmonaires rares de l'adulte, site constitutif, AP-HP, 125, rue de Stalingrad, 93000 Bobigny, France
| | - S Chauveau
- Service de pneumologie, hôpital Avicenne, centre de référence des maladies pulmonaires rares de l'adulte, site constitutif, AP-HP, 125, rue de Stalingrad, 93000 Bobigny, France
| | - W Khamis
- Service de pneumologie, hôpital Avicenne, centre de référence des maladies pulmonaires rares de l'adulte, site constitutif, AP-HP, 125, rue de Stalingrad, 93000 Bobigny, France
| | - N de Montmollin
- Service de pneumologie, hôpital Avicenne, centre de référence des maladies pulmonaires rares de l'adulte, site constitutif, AP-HP, 125, rue de Stalingrad, 93000 Bobigny, France
| | - L Sesé
- Service de pneumologie, hôpital Avicenne, centre de référence des maladies pulmonaires rares de l'adulte, site constitutif, AP-HP, 125, rue de Stalingrad, 93000 Bobigny, France
| | - B Duchemann
- Service d'oncologie, hôpital Avicenne, AP-HP, Bobigny, France
| | - H Nunes
- Service de pneumologie, hôpital Avicenne, centre de référence des maladies pulmonaires rares de l'adulte, site constitutif, AP-HP, 125, rue de Stalingrad, 93000 Bobigny, France; Inserm UMR 1272, laboratoire « hypoxie et poumon », université Paris 13, Bobigny, France
| | - Y Uzunhan
- Service de pneumologie, hôpital Avicenne, centre de référence des maladies pulmonaires rares de l'adulte, site constitutif, AP-HP, 125, rue de Stalingrad, 93000 Bobigny, France; Inserm UMR 1272, laboratoire « hypoxie et poumon », université Paris 13, Bobigny, France.
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29
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Mecoli CA, Shah AA. More Than Skin Deep: Bringing Precision Medicine to Systemic Sclerosis. Arthritis Rheumatol 2020; 72:383-385. [PMID: 31677364 PMCID: PMC7050332 DOI: 10.1002/art.41154] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 10/29/2019] [Indexed: 01/16/2023]
Affiliation(s)
| | - Ami A Shah
- Johns Hopkins University School of Medicine, Baltimore, Maryland
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30
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Kang EH, Ha YJ, Lee YJ. Autoantibody Biomarkers in Rheumatic Diseases. Int J Mol Sci 2020; 21:ijms21041382. [PMID: 32085664 PMCID: PMC7073052 DOI: 10.3390/ijms21041382] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 02/04/2020] [Accepted: 02/14/2020] [Indexed: 12/19/2022] Open
Abstract
Autoantibodies encountered in patients with systemic rheumatic diseases bear clinical significance as a biomarker to help or predict diagnosis, clinical phenotypes, prognosis, and treatment decision-making. Furthermore, evidence has accumulated regarding the active involvement of disease-specific or disease-associated autoantibodies in the pathogenic process beyond simple association with the disease, and such knowledge has become essential for us to better understand the clinical value of autoantibodies as a biomarker. This review will focus on the current update on the autoantibodies of four rheumatic diseases (rheumatoid arthritis, myositis, systemic sclerosis, and anti-neutrophil cytoplasmic antibody associated vasculitis) where there has been a tremendous progress in our understanding on their biological effects and clinical use.
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Affiliation(s)
- Eun Ha Kang
- Division of Rheumatology Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea; (Y.-J.H.); (Y.J.L.)
- Correspondence: ; Tel.: +82-31-787-7048; Fax: +82-31-787-4511
| | - You-Jung Ha
- Division of Rheumatology Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea; (Y.-J.H.); (Y.J.L.)
| | - Yun Jong Lee
- Division of Rheumatology Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea; (Y.-J.H.); (Y.J.L.)
- Department of Internal Medicine, Seoul National University, Seoul 03080, Korea
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31
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Characteristics of Systemic Sclerosis patients with positive anti-Th/To antibodies: About 6 patients and literature review. Rev Med Interne 2020; 41:440-445. [PMID: 32063422 DOI: 10.1016/j.revmed.2019.12.020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 12/11/2019] [Accepted: 12/23/2019] [Indexed: 01/20/2023]
Abstract
Among the antibodies described in Systemic Sclerosis (SSc), anti-Th/To antibodies (anti-Th/To) are rare and have been poorly studied. Thus, little is known about the profile of anti-Th/To positive patients. From our local Biobank (Marseille, France), we retrospectively selected data for 6 patients positive for anti-Th/To with an Immunodot assay. All of them suffered from SSc, sharing clinical and biological common features such as a limited cutaneous form of SSc, a decreased lung diffusing capacity and a speckled nuclear nucleolar immunofluorescence pattern of antinuclear antibodies screening on HEp-2 cells. In order to further characterize patients positive for anti-Th/To, we performed a thorough literature review. From 402 studied patients positive for anti-Th/To, we confirmed that these antibodies are associated with the limited cutaneous form of the disease (88% of the patients), and with an SSc related-pulmonary involvement (50%). The review analysis pointed out the rarity of the anti-Th/To with an estimated mean frequency of 3.4% of all SSc patients worldwide, their usual exclusivity with respect to the specific antibodies of scleroderma, and their high specificity (around 98%) for the diagnosis of SSc.
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Abstract
Systemic sclerosis (SSc) has the highest cause-specific mortality of all the connective tissue diseases, and the aetiology of this complex and heterogeneous condition remains an enigma. Current disease-modifying therapies for SSc predominantly target inflammatory and vascular pathways but have variable and unpredictable clinical efficacy, and none is curative. Moreover, many of these therapies possess undesirable safety profiles and have no appreciable effect on long-term mortality. This Review describes the most promising of the existing therapeutic targets for SSc and places them in the context of our evolving understanding of the pathophysiology of this disease. As well as taking an in-depth look at the immune, inflammatory, vascular and fibrotic pathways implicated in the pathogenesis of SSc, this Review discusses emerging treatment targets and therapeutic strategies. The article concludes with an overview of important unanswered questions in SSc research that might inform the design of future studies of treatments aimed at modifying the course of this disease.
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Airò P, Regola F, Lazzaroni MG, Tincani A, Inverardi F, Fenini MG, Ferrè F, Furloni R, Scarsi M. Incidence and prevalence of systemic sclerosis in Valcamonica, Italy, during an 18-year period. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2020; 5:51-56. [PMID: 35382405 PMCID: PMC8922587 DOI: 10.1177/2397198318819908] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 11/25/2018] [Indexed: 08/26/2024]
Abstract
Objectives To investigate the epidemiology of systemic sclerosis in Valcamonica, an Italian Alpine valley, during an 18-year-long period. Methods Patients with systemic sclerosis living in Valcamonica between 1999 and 2016 were identified by capture/recapture method using: (1) clinical databases of the only secondary Rheumatology Unit present in the valley and of the tertiary referral center for this area; (2) administrative data, extracting records with the International Classification of Diseases, 10th Revision, code for systemic sclerosis. Patients were included in the analysis when either the 1980 American Rheumatism Association classification criteria for systemic sclerosis or the 2013 American College of Rheumatology/European League Against Rheumatism criteria were satisfied. To study temporal changes, mean yearly incidence during three different 6-year interval was calculated. Prevalence rates were estimated at four different time points. Results General population with age over 14 years living in Valcamonica varied during the evaluated period between 85,168 and 91,245 inhabitants. A total of 65 patients with systemic sclerosis were identified (female 84.6%, limited cutaneous systemic sclerosis: 84.6%; anticentromere: 64.6%). Systemic sclerosis incidence and prevalence increased during the study period (p = 0.029 and p < 0.0001, respectively). The increase of incidence was accounted for by cases satisfying only the 2013 criteria, with limited cutaneous systemic sclerosis, and with anticentromere, whereas the incidence of systemic sclerosis cases classified according to the 1980 criteria did not significantly increase. The prevalence at 31 December 2016 was 58.6 (95% confidence interval, 44.8-76.6) per 100,000 persons aged >14 years. Survival at 10 years after systemic sclerosis diagnosis was 83.0% (standard error, 5.6). Conclusion Systemic sclerosis incidence and prevalence increased over time in this area, due to the increased recruitment of patients with milder forms of the disease.
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Affiliation(s)
- Paolo Airò
- Rheumatology and Clinical Immunology
Unit, Spedali Civili di Brescia, Brescia, Italy
| | - Francesca Regola
- Rheumatology and Clinical Immunology
Unit, Spedali Civili di Brescia, Brescia, Italy
- Rheumatology, University of Brescia,
Brescia, Italy
| | - Maria-Grazia Lazzaroni
- Rheumatology and Clinical Immunology
Unit, Spedali Civili di Brescia, Brescia, Italy
- Rheumatology, University of Brescia,
Brescia, Italy
| | - Angela Tincani
- Rheumatology and Clinical Immunology
Unit, Spedali Civili di Brescia, Brescia, Italy
- Rheumatology, University of Brescia,
Brescia, Italy
| | - Flora Inverardi
- Rheumatology, Internal Medicine
Department, ASST Valcamonica and Ospedale di Esine, Esine, Italy
| | | | | | - Roberto Furloni
- Rheumatology, Internal Medicine
Department, ASST Valcamonica and Ospedale di Esine, Esine, Italy
| | - Mirko Scarsi
- Rheumatology, Internal Medicine
Department, ASST Valcamonica and Ospedale di Esine, Esine, Italy
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Zuo L, Liu K, Liu H, Hu Y, Zhang Z, Qin J, Xu Q, Peng K, Jin X, Wang JH, Zhang C. Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001-2017). EClinicalMedicine 2020; 18:100238. [PMID: 31922125 PMCID: PMC6948268 DOI: 10.1016/j.eclinm.2019.100238] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 12/06/2019] [Accepted: 12/09/2019] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND The emergence and spread of HIV-1 drug resistance may compromise HIV control globally. In response to HIV/AIDS epidemic, China launched national HIV/AIDS treatment program in 2003, and started to accumulate drug resistance data since 2001. In this study we aimed to assess the level, trend and distribution of HIV-1 drug resistance during a period of 17 years from 2001 to 2017, and to characterize crucial drug resistance mutations. METHODS We systematically reviewed 4737 studies published between January 1, 2001 and March 31, 2019 in PubMed, Embase, China National Knowledge Infrastructure (CNKI), WanFang Database, Web of Science, conference abstracts from the Chinese Medical Association and the Chinese AIDS Academic Conferences, and selected 170 studies that met our study criteria. To assess the prevalence of drug resistance in whole country or a local region, we performed pooled analyses of raw data. The transformed proportions were pooled using the inverse variance fixed effects methods or the DerSimonian-Laired random effects methods. The temporal trend of transmitted drug resistance (TDR) was determined using generalized additive model implemented in the Mgcv version 1.8 package. HIV-1 genotypic resistance was analyzed using the Stanford HIVdb algorithm. FINDINGS We assembled 218 datasets from 170 selected studies (129 in Chinese and 41 in English), covering 21,451 ART-naïve and 30,475 ART-treated individuals with HIV-1 infection. The pooled prevalence of TDR was 3.0% (95%CI: 2.8-3.2), including 0.7% (95%CI: 0.4-1.0), 1.4% (95%CI: 1.3-1.6) and 0.5% (95%CI: 0.4-0.6) for nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI (NNRTI) and protease inhibitor (PI) resistance, respectively. The acquired drug resistance (ADR) prevalence was 44.7% (95%CI: 39.3-50.2), including 31.4% (95%CI: 28.2-34.6), 39.5% (95%CI: 35.6-43.5) and 1.0% (95%CI: 0.8-1.2) for NRTI, NNRTI and PI resistance, respectively. TDR and ADR prevalence had characteristic regional patterns. The worst prevalence of drug resistance occurred in Central China, and higher ADR prevalence occurred in South China than North China. TDR in whole country has risen since 2012, and this rise was driven mainly by NNRTI resistance. One NRTI-associated (M184V/I) and three NNRTI-associated (K103N/S, Y181C/I and G190A/S) mutations had high percentages in ART-naïve and ART-treated individuals, and these mutations conferred high-level resistance to 3TC, EFV and/or NVP. INTERPRETATION These findings suggest that the current available first-line ART regimens containing 3TC and/or EFV or NVP need to be revised. In addition, scale-up of multiple viral load measurements per year and drug resistance testing prior to ART initiation are recommended. Furthermore, implementation of pre-treatment education and counseling to improve patient adherence to ART is encouraged. FUNDING This work was supported by grants from the National Natural Science Foundation of China (81672033, U1302224, and 81271888) and Open Research Fund Program of the State Key Laboratory of Virology of China (2019IOV002).
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Affiliation(s)
- Lulu Zuo
- Institute of Life Science, Jiangsu University, Zhenjiang 212002, China
- College of Life Sciences, Henan Normal University, Xinxiang 453007, China
- CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China
| | - Kai Liu
- CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China
| | - Honglian Liu
- CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China
| | - Yihong Hu
- CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China
| | - Zhijie Zhang
- Department of Epidemiology and Biostatistics, Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China
| | - Jianru Qin
- College of Life Sciences, Henan Normal University, Xinxiang 453007, China
| | - Qinggang Xu
- Institute of Life Science, Jiangsu University, Zhenjiang 212002, China
| | - Ke Peng
- State Key Laboratory of Virology and Joint Laboratory of Invertebrate Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
| | - Xia Jin
- CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China
| | - Jian-Hua Wang
- CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China
| | - Chiyu Zhang
- CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China
- Corresponding author.
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Liu C, Hou Y, Xu D, Li L, Zhang Y, Cheng L, Yan S, Zhang F, Li Y. Analysis of anti-RNA polymerase III antibodies in Chinese Han systemic sclerosis patients. Clin Rheumatol 2019; 39:1191-1197. [PMID: 31858335 DOI: 10.1007/s10067-019-04806-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Revised: 09/12/2019] [Accepted: 10/02/2019] [Indexed: 12/22/2022]
Abstract
OBJECTIVES This study aimed to assess the prevalence and clinical correlation of anti-RNA polymerase III antibodies (anti-RNAP III) in Chinese Han systemic sclerosis (SSc) patients. METHODS Serum samples from 236 patients with SSc, 125 patients with connective tissue diseases (CTD), and 166 healthy controls (HCs), recruited from Peking Union Medical College Hospital and 21 other medical centers in China, were tested for antibodies to RNA polymerase III by means of a line immunoassay (LIA) or an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS Anti-RNAP III antibodies were found in 14/236 SSc patients (5.93%), 1/125 (0.80%) CTD patients, and 0/166 (0.00%) HCs. The prevalence of anti-RNAP III was higher in SSc patients than in the CTD and HC groups (p = 0.02, p = 0.001, respectively). Renal crisis was significantly more common in patients with anti-RNAP III than patients without anti-RNAP III (42.9 vs. 4.1%, p < 0.0001). Gastrointestinal involvement was significantly more common in patients without anti-RNAP III than patients with anti-RNAP III (53.6 vs. 21.4%, p = 0.039). There was good agreement between the ELISA and line immunoassay (LIA) detection capabilities for anti-RNAP III. CONCLUSIONS The anti-RNAP III antibody, which was detected by ELISA, has diagnostic value for SSc and predictive value for SSc-related renal crisis. Both ELISA and LIA are very reliable methods for anti-RNAP III.Key Points• The prevalence of anti-RNAP III antibody was determined in Chinese SSc patients and performed ethnic differences.• The clinical association between anti-RNAP III antibody and Chinese SSc patients was evaluated in this research.• Methodological consistency of detection of anti-RNAP III antibody using commercial ELISA and LIA methods was evaluated in this research.
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Affiliation(s)
- Chenxi Liu
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, 1 Shuaifuyuan, Dongcheng District, 100730, Beijing, People's Republic of China
| | - Yong Hou
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 1 Shuaifuyuan, Dongcheng District, 100730, Beijing, People's Republic of China
| | - Dong Xu
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 1 Shuaifuyuan, Dongcheng District, 100730, Beijing, People's Republic of China
| | - Liubing Li
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, 1 Shuaifuyuan, Dongcheng District, 100730, Beijing, People's Republic of China
| | - Yanfang Zhang
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, 1 Shuaifuyuan, Dongcheng District, 100730, Beijing, People's Republic of China
| | - Linlin Cheng
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, 1 Shuaifuyuan, Dongcheng District, 100730, Beijing, People's Republic of China
| | - Songxin Yan
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, 1 Shuaifuyuan, Dongcheng District, 100730, Beijing, People's Republic of China
| | - Fengchun Zhang
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 1 Shuaifuyuan, Dongcheng District, 100730, Beijing, People's Republic of China.
| | - Yongzhe Li
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, 1 Shuaifuyuan, Dongcheng District, 100730, Beijing, People's Republic of China.
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Sobanski V, Giovannelli J, Allanore Y, Riemekasten G, Airò P, Vettori S, Cozzi F, Distler O, Matucci-Cerinic M, Denton C, Launay D, Hachulla E. Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis. Arthritis Rheumatol 2019; 71:1553-1570. [PMID: 30969034 PMCID: PMC6771590 DOI: 10.1002/art.40906] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 04/04/2019] [Indexed: 01/26/2023]
Abstract
Objective Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. Methods A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty‐four clinical and serologic variables were used for clustering. Results Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. Conclusion Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis.
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Affiliation(s)
- Vincent Sobanski
- Université Lille, INSERM U995 LIRIC, CHU Lille, and Referral Center for Rare Systemic Autoimmune Diseases North and North-West of France, Lille, France
| | | | - Yannick Allanore
- Hôpital Cochin, APHP, and Université Paris Descartes, Paris, France
| | | | - Paolo Airò
- Spedali Civili di Brescia, Brescia, Italy
| | | | | | | | | | | | - David Launay
- Université Lille, INSERM U995 LIRIC, CHU Lille, and Referral Center for Rare Systemic Autoimmune Diseases North and North-West of France, Lille, France
| | - Eric Hachulla
- Université Lille, INSERM U995 LIRIC, CHU Lille, and Referral Center for Rare Systemic Autoimmune Diseases North and North-West of France, Lille, France
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Allanore Y, Gharibdoost F, Jamshidi AR, Javinani A, Avouac J, Rastkar E, Hooshmandi S, Kavosi H. Comparison of the clinical phenotype of systemic sclerosis patients in Iran and France in two university centers. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2019; 4:149-159. [PMID: 35382390 PMCID: PMC8922647 DOI: 10.1177/2397198318809224] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 09/30/2018] [Indexed: 06/29/2024]
Abstract
OBJECTIVES Systemic sclerosis is a severe and rare chronic auto-immune multisystem disorder characterized by vasculopathy and skin stiffness. Ethnic and geographical origin can influence the outcomes. In this study, we compared the phenotypic characteristics of Iranian and French patients. METHODS This cross-sectional study was performed on 200 Iranian and 268 French systemic sclerosis patients. Iranian patients collected from the Iranian systemic sclerosis cohort of the Rheumatology Research Center, Shariati hospital, Tehran University of Medical Sciences. The French population was monocentric, and it was constituted by the patients included locally in the EUSTAR database in December 2016. RESULTS The mean age at onset was significantly lower in Iranian patients (35.58 ± 11.68 vs 47.06 ± 13.54, p-value < 0.001). The female-to-male ratio was approximately 5.2:1 and was not different in the two populations. The prevalence of diffuse cutaneous systemic sclerosis was significantly higher in Iranian patients (60.2% vs 42.85%, p-value < 0.001). Calcinosis cutis and joint synovitis were more prevalent in French patients (p-value = 0.013, <0.001). The positivity of anti-topoisomerase antibody was higher in Iranian patients, whereas the anti-centromere antibody predominated in French cases (p-value < 0.001). Restrictive pattern of pulmonary function test was more common in Iranian patients (p-value < 0.001), while estimated pulmonary arterial pressure by echocardiography was higher in French patients (p-value < 0.001). CONCLUSION It seems that systemic sclerosis occurred in younger ages among Iranian female with the predominance of diffuse cutaneous subtype. In addition, lung interstitial disease appeared to be more prevalent and severe in Iranians than French patients.
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Affiliation(s)
- Yannick Allanore
- Department of Rheumatology, Cochin Hospital, Paris Descartes University, Paris, France
| | - Farhad Gharibdoost
- Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Reza Jamshidi
- Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Javinani
- Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Jérôme Avouac
- Department of Rheumatology, Cochin Hospital, Paris Descartes University, Paris, France
| | - Elnaz Rastkar
- Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Sadid Hooshmandi
- Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hoda Kavosi
- Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Abstract
Connective tissue diseases (CTDs), also known as systemic autoimmune diseases, involve a variety of autoantibodies against cellular components. An important factor regarding these autoantibodies is that each antibody is exclusively related to a certain clinical feature of the disease type, which may prove useful in clinical practice. Thus far, more than 100 types of autoantibodies have been found in CTDs, and most of their target antigens have been identified. Many of these autoantigens are enzymes or regulators involved in important cellular functions, such as gene replication, transcription, repair/recombination, RNA processing, and protein synthesis, as well as proteins that form complexes with RNA and DNA. This article reviews the autoantibodies for each CTD, along with an assessment of their clinical significance, and provides suggestions regarding their utilization for clinical practice.
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Affiliation(s)
- Kosaku Murakami
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Japan
| | - Tsuneyo Mimori
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Japan
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Sobanski V, Lemaire-Olivier A, Giovannelli J, Dauchet L, Simon M, Lopez B, Yelnik C, Lambert M, Hatron PY, Hachulla E, Dubucquoi S, Launay D. Prevalence and Clinical Associations of Antiphospholipid Antibodies in Systemic Sclerosis: New Data From a French Cross-Sectional Study, Systematic Review, and Meta-Analysis. Front Immunol 2018; 9:2457. [PMID: 30464761 PMCID: PMC6234954 DOI: 10.3389/fimmu.2018.02457] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 10/04/2018] [Indexed: 02/06/2023] Open
Abstract
Objectives: Antiphospholipid antibodies (aPL) can be present in the sera of systemic sclerosis (SSc) patients. This study aimed to determine the prevalence of aPL in a cross-sectional study of SSc patients, to assess their clinical associations, to perform a systematic review of published reports and a meta-analysis to estimate the worldwide prevalence of aPL in SSc. Methods: Two-hundred and forty-nine SSc patients were consecutively tested once for lupus anticoagulant (LA), anticardiolipin (aCL), and anti-β2glycoprotein I (anti-β2GpI) antibodies. Clinical associations with aPL positivity were studied using a logistic regression model. A systematic review of the literature was carried out in PubMed and Embase. Meta-analysis was performed using number of aPL positive (at least one of the three antibodies positive) and negative patients. Meta-regression was used to study potential factors explaining the heterogeneity between studies. Results: In our cross-sectional study, aPL positivity was found in 16 patients (prevalence 6.4%; 95%CI [3.8-10.4]). In multivariate analysis, there was a significant association between aPL positivity and venous thrombosis (VT) (OR 6.25 [1.18-33.00]; p = 0.028) and miscarriage (OR 5.43; 95%CI [1.31-22.13]; p = 0.017). Twenty-four studies were included in the meta-analysis, representing a total population of 3036 SSc patients. The overall pooled prevalence of aPL in SSc was 14% (9-20) with a high degree of heterogeneity among studies. Conclusion: This study found a prevalence of aPL positivity in our SSc population of 6.4% (3.8-10.4) and an overall worldwide pooled prevalence of 14% (9-20). In our SSc population, aPL positivity was associated with VT and miscarriage. These data provide additional insights into the role of aPL in the vasculopathy observed in SSc.
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Affiliation(s)
- Vincent Sobanski
- Univ. Lille, U995, Lille Inflammation Research International Center, Lille, France.,Inserm, Lille, France.,CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-Immunes Rares (Sclérodermie Systémique), Lille, France
| | - Angélique Lemaire-Olivier
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-Immunes Rares (Sclérodermie Systémique), Lille, France
| | - Jonathan Giovannelli
- Univ. Lille, U995, Lille Inflammation Research International Center, Lille, France.,Inserm, Lille, France.,CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-Immunes Rares (Sclérodermie Systémique), Lille, France
| | - Luc Dauchet
- Inserm UMR1167, RID-AGE, Risk Factors and Molecular Determinants of Aging-Related Diseases, Université de Lille, Centre Hosp. Univ. Lille, Institut Pasteur de Lille, Lille, France
| | - Myriam Simon
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-Immunes Rares (Sclérodermie Systémique), Lille, France
| | - Benjamin Lopez
- Univ. Lille, U995, Lille Inflammation Research International Center, Lille, France.,Inserm, Lille, France.,CHU Lille, Institut d'Immunologie, Lille, France
| | - Cécile Yelnik
- Univ. Lille, U995, Lille Inflammation Research International Center, Lille, France.,Inserm, Lille, France.,CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-Immunes Rares (Sclérodermie Systémique), Lille, France
| | - Marc Lambert
- Univ. Lille, U995, Lille Inflammation Research International Center, Lille, France.,Inserm, Lille, France.,CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-Immunes Rares (Sclérodermie Systémique), Lille, France
| | - Pierre-Yves Hatron
- CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-Immunes Rares (Sclérodermie Systémique), Lille, France
| | - Eric Hachulla
- Univ. Lille, U995, Lille Inflammation Research International Center, Lille, France.,Inserm, Lille, France.,CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-Immunes Rares (Sclérodermie Systémique), Lille, France
| | - Sylvain Dubucquoi
- Univ. Lille, U995, Lille Inflammation Research International Center, Lille, France.,Inserm, Lille, France.,CHU Lille, Institut d'Immunologie, Lille, France
| | - David Launay
- Univ. Lille, U995, Lille Inflammation Research International Center, Lille, France.,Inserm, Lille, France.,CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.,Centre National de Référence Maladies Systémiques et Auto-Immunes Rares (Sclérodermie Systémique), Lille, France
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Lazzaroni MG, Airò P. Anti-RNA polymerase III antibodies in patients with suspected and definite systemic sclerosis: Why and how to screen. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2018; 3:214-220. [PMID: 35382018 PMCID: PMC8922599 DOI: 10.1177/2397198318786158] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Accepted: 06/08/2018] [Indexed: 08/26/2024]
Abstract
Anti-RNA Polymerase III antibodies are the most frequent anti-nuclear antibodies in systemic sclerosis, after anti-centromere and anti-Topoisomerase I. Considering their specificity for systemic sclerosis, they have been included in 2013 American College of Rheumatology/European League Against Rheumatism classification criteria for systemic sclerosis. They were first identified in 1993 using an immunoprecipitation method; the subsequent diffusion of commercial assays, based on the enzyme-linked immunosorbent assay or multiplex line immunoblot techniques, has allowed an increasing number of systemic sclerosis patients to be tested for this autoantibody; nevertheless, the diffusion of this test in systemic sclerosis patients is probably still sub-optimal. Anti-RNA Polymerase III antibodies have been associated with important clinical manifestations: rapid and diffuse cutaneous involvement, joint contractures, scleroderma renal crisis, gastric antral vascular ectasia and malignancies synchronous to systemic sclerosis onset. Moreover, other possible clinical associations, including pulmonary hypertension, still need confirmation. Since the correct approach for screening for anti- RNA Polymerase III antibodies in patients with suspected or definite systemic sclerosis is still debated, possible strategies are proposed here. Moreover, issues that are still controversial are discussed, including the interpretation of multiple simultaneous positivity for anti-RNA Polymerase III antibodies and other autoantibodies in line immunoassay, and the possible relevance of anti-RNA Polymerase III antibodies titre.
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Affiliation(s)
- Maria-Grazia Lazzaroni
- Rheumatology and Clinical Immunology Unit, Spedali Civili and University of Brescia, Brescia, Italy
| | - Paolo Airò
- Rheumatology and Clinical Immunology Unit, Spedali Civili and University of Brescia, Brescia, Italy
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Hamaguchi Y, Takehara K. Anti-nuclear autoantibodies in systemic sclerosis : News and perspectives. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2018; 3:201-213. [PMID: 35382013 PMCID: PMC8922602 DOI: 10.1177/2397198318783930] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Accepted: 05/20/2018] [Indexed: 02/01/2024]
Abstract
Systemic sclerosis is a connective tissue disorder characterized by microvascular damage and excessive fibrosis of the skin and internal organs. One hallmark of the immunological abnormalities in systemic sclerosis is the presence of anti-nuclear antibodies, which are detected in more than 90% of patients with systemic sclerosis. Anti-centromere antibodies, anti-DNA topoisomerase I antibodies, and anti-RNA polymerase III antibodies are the predominant anti-nuclear antibodies found in systemic sclerosis patients. Other systemic sclerosis-related anti-nuclear antibodies include those targeted against U3 ribonucleoprotein, Th/To, U11/U12 ribonucleoprotein, and eukaryotic initiation factor 2B. Anti-U1 ribonucleoprotein, anti-Ku antibodies, anti-PM-Scl, and anti-RuvBL1/2 antibodies are associated with systemic sclerosis overlap syndrome. Anti-human upstream binding factor, anti-Ro52/TRIM21, anti-B23, and anti-centriole antibodies do not have specificity to systemic sclerosis, but are sometimes detected in sera from patients with systemic sclerosis. Identification of each systemic sclerosis-related antibody is useful to diagnose and predict organ involvement, since the particular type of systemic sclerosis-related antibodies is often predictive of clinical features, severity, and prognosis. The clinical phenotypes are largely influenced by ethnicity. Currently, an immunoprecipitation assay is necessary to detect most systemic sclerosis-related antibodies; therefore, the establishment of an easy, reliable, and simple screening system is warranted.
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Affiliation(s)
- Yasuhito Hamaguchi
- Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Japan
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Asano Y, Jinnin M, Kawaguchi Y, Kuwana M, Goto D, Sato S, Takehara K, Hatano M, Fujimoto M, Mugii N, Ihn H. Diagnostic criteria, severity classification and guidelines of systemic sclerosis. J Dermatol 2018; 45:633-691. [PMID: 29687465 DOI: 10.1111/1346-8138.14162] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 11/06/2017] [Indexed: 01/17/2023]
Abstract
Several effective drugs have been identified for the treatment of systemic sclerosis (SSc). However, in advanced cases, not only their effectiveness is reduced but they may be also harmful due to their side-effects. Therefore, early diagnosis and early treatment is most important for the treatment of SSc. We established diagnostic criteria for SSc in 2003 and early diagnostic criteria for SSc in 2011, for the purpose of developing evaluation of each organ in SSc. Moreover, in November 2013, the American College of Rheumatology and the European Rheumatology Association jointly developed new diagnostic criteria for increasing their sensitivity and specificity, so we revised our diagnostic criteria and severity classification of SSc. Furthermore, we have revised the clinical guideline based on the newest evidence. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of SSc.
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Affiliation(s)
- Yoshihide Asano
- Department of Dermatology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masatoshi Jinnin
- Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yasushi Kawaguchi
- Institute of Rheumatology, Tokyo Woman's Medical University, Tokyo, Japan
| | - Masataka Kuwana
- Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan
| | - Daisuke Goto
- Department of Rheumatology, Faculty of Medicine, Univertity of Tsukuba, Ibaraki, Japan
| | - Shinichi Sato
- Department of Dermatology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Takehara
- Department of Molecular Pathology of Skin, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan
| | - Masaru Hatano
- Graduate School of Medicine Department of Therapeutic Strategy for Heart Failure, The University of Tokyo, Tokyo, Japan
| | - Manabu Fujimoto
- Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Naoki Mugii
- Section of Rehabilitation, Kanazawa University Hospital, Ishikawa, Japan
| | - Hironobu Ihn
- Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
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Joven BE, Escribano P, Andreu JL, Loza E, Jimenez C, de Yebenes MJG, Ruiz-Cano MJ, Carmona L, Carreira PE. 2013 ACR/EULAR systemic sclerosis classification criteria in patients with associated pulmonary arterial hypertension. Semin Arthritis Rheum 2018; 47:870-876. [DOI: 10.1016/j.semarthrit.2017.10.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 09/11/2017] [Accepted: 10/11/2017] [Indexed: 01/27/2023]
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Ingegnoli F, Ughi N, Mihai C. Update on the epidemiology, risk factors, and disease outcomes of systemic sclerosis. Best Pract Res Clin Rheumatol 2018; 32:223-240. [DOI: 10.1016/j.berh.2018.08.005] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 07/22/2018] [Accepted: 07/26/2018] [Indexed: 12/12/2022]
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Didier K, Bolko L, Giusti D, Toquet S, Robbins A, Antonicelli F, Servettaz A. Autoantibodies Associated With Connective Tissue Diseases: What Meaning for Clinicians? Front Immunol 2018; 9:541. [PMID: 29632529 PMCID: PMC5879136 DOI: 10.3389/fimmu.2018.00541] [Citation(s) in RCA: 97] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Accepted: 03/02/2018] [Indexed: 02/06/2023] Open
Abstract
Connective tissue diseases (CTDs) such as systemic lupus erythematosus, systemic sclerosis, myositis, Sjögren's syndrome, and rheumatoid arthritis are systemic diseases which are often associated with a challenge in diagnosis. Autoantibodies (AAbs) can be detected in these diseases and help clinicians in their diagnosis. Actually, pathophysiology of these diseases is associated with the presence of antinuclear antibodies. In the last decades, many new antibodies were discovered, but their implication in pathogenesis of CTDs remains unclear. Furthermore, the classification of these AAbs is nowadays misused, as their targets can be localized outside of the nuclear compartment. Interestingly, in most cases, each antibody is associated with a specific phenotype in CTDs and therefore help in better defining either the disease subtypes or diseases activity and outcome. Because of recent progresses in their detection and in the comprehension of their pathogenesis implication in CTD-associated antibodies, clinicians should pay attention to the presence of these different AAbs to improve patient's management. In this review, we propose to focus on the different phenotypes and features associated with each autoantibody used in clinical practice in those CTDs.
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Affiliation(s)
- Kevin Didier
- Department of Internal Medicine, Infectious Diseases, and Clinical Immunology, Reims Teaching Hospitals, Robert Debré Hospital, Reims, France
| | - Loïs Bolko
- Rheumatology Department, Maison Blanche Hospital, Reims University Hospitals, Reims, France
| | - Delphine Giusti
- Laboratory of Dermatology, Faculty of Medicine, EA7319, University of Reims Champagne-Ardenne, Reims, France.,Laboratory of Immunology, Reims University Hospital, University of Reims Champagne-Ardenne, Reims, France
| | - Segolene Toquet
- Department of Internal Medicine, CHU de Reims, Reims, France
| | - Ailsa Robbins
- Department of Internal Medicine, Infectious Diseases, and Clinical Immunology, Reims Teaching Hospitals, Robert Debré Hospital, Reims, France
| | - Frank Antonicelli
- Laboratory of Dermatology, Faculty of Medicine, EA7319, University of Reims Champagne-Ardenne, Reims, France.,Department of Biological Sciences, Immunology, UFR Odontology, University of Reims Champagne-Ardenne, Reims, France
| | - Amelie Servettaz
- Department of Internal Medicine, Infectious Diseases, and Clinical Immunology, Reims Teaching Hospitals, Robert Debré Hospital, Reims, France.,Laboratory of Dermatology, Faculty of Medicine, EA7319, University of Reims Champagne-Ardenne, Reims, France
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Bruni C, Cuomo G, Rossi FW, Praino E, Bellando-Randone S. Kidney involvement in systemic sclerosis: From pathogenesis to treatment. JOURNAL OF SCLERODERMA AND RELATED DISORDERS 2018; 3:43-52. [PMID: 35382123 PMCID: PMC8892882 DOI: 10.1177/2397198318758607] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/19/2018] [Indexed: 11/09/2023]
Abstract
Among all possible systemic sclerosis internal organ complications, kidney involvement is frequently neglected or underestimated, except for the life-threatening scleroderma renal crisis. Fortunately, this severe clinical presentation is nowadays better controlled with available treatments, in particular angiotensin-converting enzyme inhibitors, and this has led to a reduction in its short- and longer-term mortality. Pathogenetic determinants are not well understood and many different other kidney involvements are possible in systemic sclerosis, including proteinuria, albuminuria, reduction of renal filtration, autoantibodies-related glomerulonephritis, and drug-related side effects. Different serological and radiological methods of evaluations are nowadays available, some representing promising diagnostic tool and prognostic outcome measure. Except for angiotensin-converting enzyme inhibitors in scleroderma renal crisis, no other treatment is currently recommended for treatment of kidney involvement in systemic sclerosis. For this reason, further studies are necessary to investigate its prognostic impact, in particular in combination with other systemic sclerosis-related internal organ manifestations. This review summarizes current available literature on kidney involvement in systemic sclerosis.
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Affiliation(s)
- Cosimo Bruni
- Department of Experimental and
Clinical Medicine, Division of Rheumatology, University of Florence,
Florence - Italy
- Department of Geriatric Medicine,
Division of Rheumatology and Scleroderma Unit, Azienda Ospedaliero
Universitaria Careggi, Florence - Italy
| | - Giovanna Cuomo
- Department of Clinical and
Experimental Internal Medicine “F. Magrassi,” University of Study of
Campania “Luigi Vanvitelli,” Naples - Italy
| | - Francesca W. Rossi
- Department of Translational
Medical Sciences and Center for Basic and Clinical Immunology Research
(CISI), WAO Center of Excellence, University of Naples Federico II, Naples -
Italy
| | - Emanuela Praino
- Department of Emergency and Organ
Transplantation, Rheumatology Unit, University of Bari, Bari - Italy
| | - Silvia Bellando-Randone
- Department of Experimental and
Clinical Medicine, Division of Rheumatology, University of Florence,
Florence - Italy
- Department of Geriatric Medicine,
Division of Rheumatology and Scleroderma Unit, Azienda Ospedaliero
Universitaria Careggi, Florence - Italy
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Forestier A, Guerrier T, Jouvray M, Giovannelli J, Lefèvre G, Sobanski V, Hauspie C, Hachulla E, Hatron PY, Zéphir H, Vermersch P, Labalette M, Launay D, Dubucquoi S. Altered B lymphocyte homeostasis and functions in systemic sclerosis. Autoimmun Rev 2018; 17:244-255. [PMID: 29343447 DOI: 10.1016/j.autrev.2017.10.015] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 10/26/2017] [Indexed: 12/20/2022]
Abstract
Beyond the production of autoantibodies, B-cells are thought to play a role in systemic sclerosis (SSc) by secreting proinflammatory/profibrotic cytokines. B-cells are a heterogeneous population with different subsets distinguished by their phenotypes and cytokine production. Data about B-cell subsets, cytokine production and intracellular pathways leading to this production are scarce in SSc. The aim of our study was to describe B-cell homeostasis, activation, proliferation, cytokine production in B-cells and serum and B-cell intracellular signaling pathways in SSc. We hypothezided that B-cell homeostasis and cytokine production were altered in SSc and could be explained by serum cytokine as well as by intracellular signaling pathway abnormalities. Forty SSc patients and 20 healthy controls (HC) were prospectively included. B-cell subsets were determined by flow cytometry using CD19, CD21, CD24, CD38, CD27, IgM and IgD. CD25, CD80, CD95, HLA-DR were used to assess B-cell activation. Intracellular production of IL-10 and IL-6 were assessed by flow cytometry after TLR9 and CD40 stimulation. IL-6, IL-10, Ki67, Bcl2 mRNA were quantified in B-cells. Cytokine production was also assessed in sera and supernatants of B-cell culture, using a multiplex approach. Signaling pathways were studied through phosphorylation of mTOR, ERK, STAT3, STAT5 using a flow cytometry approach. We found that SSc patients exhibited an altered peripheral blood B-cell subset distribution, with decreased memory B-cells but increased proportion of naive and CD21LoCD38Lo B-cell subsets. We observed an increased expression of activation markers (CD80, CD95, HLA-DR) on some B-cell subsets, mainly the memory B-cells. Secretion of IL-6, BAFF and CXCL13 were increased in SSc sera. There was no correlation between the peripheral blood B-cell subsets and the serum concentrations of these cytokines. After stimulation, we observed a lower proportion of IL-10 and IL-6 producing B-cells in SSc. Finally, we observed a significant decrease of mTOR phosphorylation in SSc patient B-cells. In conclusion, we observed an altered B-cell homeostasis in SSc patients compared to HC. Memory B-cells were both decreased and activated in patients. IL-10 producing B-cells were decreased in SSc. This decrease was associated with an alteration of mTOR phosphorylation in B-cells. Conversely, there was no correlation between serum cytokine profile and B-cell homeostasis alterations.
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Affiliation(s)
- Alexandra Forestier
- Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France; Inserm, U995, F-59000 Lille, France; CHU Lille, Département de médecine interne et immunologie clinique, F-59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares, France
| | - Thomas Guerrier
- Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France; Inserm, U995, F-59000 Lille, France
| | - Mathieu Jouvray
- Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France; Inserm, U995, F-59000 Lille, France; CHU Lille, Département de médecine interne et immunologie clinique, F-59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares, France
| | - Jonathan Giovannelli
- Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France; Inserm, U995, F-59000 Lille, France; CHU Lille, Département de médecine interne et immunologie clinique, F-59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares, France
| | - Guillaume Lefèvre
- Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France; Inserm, U995, F-59000 Lille, France; CHU Lille, Département de médecine interne et immunologie clinique, F-59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares, France; CHU Lille, Institut d'immunologie, F-59000 Lille, France
| | - Vincent Sobanski
- Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France; Inserm, U995, F-59000 Lille, France; CHU Lille, Département de médecine interne et immunologie clinique, F-59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares, France
| | - Carine Hauspie
- Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France; Inserm, U995, F-59000 Lille, France; CHU Lille, Institut d'immunologie, F-59000 Lille, France
| | - Eric Hachulla
- Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France; Inserm, U995, F-59000 Lille, France; CHU Lille, Département de médecine interne et immunologie clinique, F-59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares, France
| | - Pierre-Yves Hatron
- CHU Lille, Département de médecine interne et immunologie clinique, F-59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares, France
| | - Hélène Zéphir
- Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France; Inserm, U995, F-59000 Lille, France; CHU Lille, Service de neurologie, F-59000 Lille, France
| | - Patrick Vermersch
- Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France; Inserm, U995, F-59000 Lille, France; CHU Lille, Service de neurologie, F-59000 Lille, France
| | - Myriam Labalette
- Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France; Inserm, U995, F-59000 Lille, France; CHU Lille, Institut d'immunologie, F-59000 Lille, France
| | - David Launay
- Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France; Inserm, U995, F-59000 Lille, France; CHU Lille, Département de médecine interne et immunologie clinique, F-59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares, France.
| | - Sylvain Dubucquoi
- Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), F-59000 Lille, France; Inserm, U995, F-59000 Lille, France; CHU Lille, Institut d'immunologie, F-59000 Lille, France
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Benyamine A, Bertin D, Heim X, Granel B, Bardin N. Should we look for anti-RNA polymerase III antibodies in systemic sclerosis patients with anti-centromere or anti-topoisomerase I antibodies? Eur J Intern Med 2017; 44:e42-e44. [PMID: 28781194 DOI: 10.1016/j.ejim.2017.07.033] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 07/23/2017] [Accepted: 07/26/2017] [Indexed: 11/19/2022]
Affiliation(s)
- Audrey Benyamine
- Aix Marseille University, INSERM, VRCM, UMR_S 1076, Marseille, France; APHM, Hôpital Nord, Médecine interne, Marseille, France.
| | - Daniel Bertin
- APHM, Hôpital La Conception, Laboratoire d'Immunologie, Marseille, France
| | - Xavier Heim
- APHM, Hôpital La Conception, Laboratoire d'Immunologie, Marseille, France
| | - Brigitte Granel
- Aix Marseille University, INSERM, VRCM, UMR_S 1076, Marseille, France; APHM, Hôpital Nord, Médecine interne, Marseille, France
| | - Nathalie Bardin
- Aix Marseille University, INSERM, VRCM, UMR_S 1076, Marseille, France; APHM, Hôpital La Conception, Laboratoire d'Immunologie, Marseille, France
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Systemic sclerosis and the gastrointestinal tract. GASTROENTEROLOGY REVIEW 2017; 12:163-168. [PMID: 29123575 PMCID: PMC5672703 DOI: 10.5114/pg.2017.70467] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Accepted: 06/01/2017] [Indexed: 02/07/2023]
Abstract
Systemic sclerosis (SSc) is an autoimmunological disease of unknown origin with complex pathogenesis and multiple organ involvement. It is characterised by vascular and immunological abnormalities leading to fibrosis of the skin and internal organs. It is a rather rare disease with a prevalence of around 20 per 100,000. The disease results in heterogeneous clinical findings and different courses. Systemic sclerosis usually begins with the onset of Raynaud’s phenomenon (RP), followed by skin sclerosis and internal organ involvement, although it may appear synchronously with RP. Gastrointestinal involvement is a serious and prevalent complication of SSc, and the oesophagus is the most frequently affected organ. Both limited and diffuse cutaneous SSc involve internal organs, with the involvement of the gastrointestinal tract as a leading cause of morbidity. At present, treatment is mainly symptomatic with no disease-modifying drugs.
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50
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Kuwana M. Circulating Anti-Nuclear Antibodies in Systemic Sclerosis: Utility in Diagnosis and Disease Subsetting. J NIPPON MED SCH 2017; 84:56-63. [PMID: 28502960 DOI: 10.1272/jnms.84.56] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The presence of circulating anti-nuclear antibodies (ANAs) is a hallmark of immune dysregulation in patients with systemic sclerosis (SSc). Currently, a variety of SSc-specific ANAs, including anticentromere, anti-topoisomerase I, and anti-RNA polymerase III antibodies, have been well characterized, and their commercial kits are available worldwide. Since these autoantibodies are specifically detected in SSc patients and are associated with unique sets of disease manifestations, they are widely used in routine clinical practice for diagnosis, clinical subgrouping, and prediction of future organ involvements and prognosis. In addition, SSc-specific ANAs are also useful in predicting future development of SSc in patients with Raynaud's phenomenon without any scleroderma skin changes, because their production often precedes onset of SSc symptoms. Application of circulating SSc-specific ANA measurement to clinical practice has greatly improved patient care, but utility of the autoantibody testing could be maximized by combining other clinical information, such as degree and extent of skin thickness and disease duration.
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Affiliation(s)
- Masataka Kuwana
- Department of Allergy and Rheumatology, Nippon Medical School
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