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Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis
BACKGROUND: Systemic sclerosis (SSc) belongs to the group of connective tissue diseases and is associated with the occurrence of disease-specific autoantibodies. Although it is still controversial whether these antibodies contribute to pathogenesis, there are new insights into the development of the...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846214/ https://www.ncbi.nlm.nih.gov/pubmed/36685532 http://dx.doi.org/10.3389/fimmu.2022.1045523 |
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author | Höppner, Jakob Tabeling, Christoph Casteleyn, Vincent Kedor, Claudia Windisch, Wolfram Burmester, Gerd Rüdiger Huscher, Dörte Siegert, Elise |
author_facet | Höppner, Jakob Tabeling, Christoph Casteleyn, Vincent Kedor, Claudia Windisch, Wolfram Burmester, Gerd Rüdiger Huscher, Dörte Siegert, Elise |
author_sort | Höppner, Jakob |
collection | PubMed |
description | BACKGROUND: Systemic sclerosis (SSc) belongs to the group of connective tissue diseases and is associated with the occurrence of disease-specific autoantibodies. Although it is still controversial whether these antibodies contribute to pathogenesis, there are new insights into the development of these specific antibodies and their possible pathophysiological properties. Interestingly, they are associated with specific clinical manifestations, but for some rarer antibodies this association is not fully clarified. The aim of this study is a comprehensive analysis of the serum autoantibody status in patients with SSc followed by correlation analyses of autoantibodies with the clinical course of the disease. METHODS: Serum from SSc patients was analyzed using a line blot (EUROLINE, EUROIMMUN AG) for SSc-related autoantibodies. Autoantibodies to centromere, Topo-1, antimitochondrial antibodies (AMA) M2 subunit, angiotensin II type 1 receptors (AT(1)R) and endothelin-1 type-A-receptors (ET(A)R) were also determined by ELISA. We formed immunological clusters and used principal components analysis (PCA) to assign specific clinical characteristics to these clusters. RESULTS: A total of 372 SSc patients were included. 95.3% of the patients were antinuclear antibody positive and in 333 patients at least one SSc specific antibody could be detected. Four immunological clusters could be found by PCA. Centromere, Topo-1 and RP3 all formed own clusters, which are associated with distinct clinical phenotypes. We found that patients with an inverted phenotype, such as limited cutaneous SSc patients within the Topo-1 cluster show an increased risk for interstital lung disease compared to ACA positive patients. Anti-AT(1)R and anti-ET(A)R autoantibodies were measured in 176 SSc patients; no association with SSc disease manifestation was found. SSc patients with AMA-M2 antibodies showed an increased risk of cardiovascular events. CONCLUSION: In our in large cluster analysis, which included an extended autoantibody profile, we were able to show that serologic status of SSc patients provides important clues to disease manifestation, co-morbidities and complications. Line blot was a reliable technique to detect autoantibodies in SSc and detected rarer autoantibodies in 42% of our patients. |
format | Online Article Text |
id | pubmed-9846214 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98462142023-01-19 Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis Höppner, Jakob Tabeling, Christoph Casteleyn, Vincent Kedor, Claudia Windisch, Wolfram Burmester, Gerd Rüdiger Huscher, Dörte Siegert, Elise Front Immunol Immunology BACKGROUND: Systemic sclerosis (SSc) belongs to the group of connective tissue diseases and is associated with the occurrence of disease-specific autoantibodies. Although it is still controversial whether these antibodies contribute to pathogenesis, there are new insights into the development of these specific antibodies and their possible pathophysiological properties. Interestingly, they are associated with specific clinical manifestations, but for some rarer antibodies this association is not fully clarified. The aim of this study is a comprehensive analysis of the serum autoantibody status in patients with SSc followed by correlation analyses of autoantibodies with the clinical course of the disease. METHODS: Serum from SSc patients was analyzed using a line blot (EUROLINE, EUROIMMUN AG) for SSc-related autoantibodies. Autoantibodies to centromere, Topo-1, antimitochondrial antibodies (AMA) M2 subunit, angiotensin II type 1 receptors (AT(1)R) and endothelin-1 type-A-receptors (ET(A)R) were also determined by ELISA. We formed immunological clusters and used principal components analysis (PCA) to assign specific clinical characteristics to these clusters. RESULTS: A total of 372 SSc patients were included. 95.3% of the patients were antinuclear antibody positive and in 333 patients at least one SSc specific antibody could be detected. Four immunological clusters could be found by PCA. Centromere, Topo-1 and RP3 all formed own clusters, which are associated with distinct clinical phenotypes. We found that patients with an inverted phenotype, such as limited cutaneous SSc patients within the Topo-1 cluster show an increased risk for interstital lung disease compared to ACA positive patients. Anti-AT(1)R and anti-ET(A)R autoantibodies were measured in 176 SSc patients; no association with SSc disease manifestation was found. SSc patients with AMA-M2 antibodies showed an increased risk of cardiovascular events. CONCLUSION: In our in large cluster analysis, which included an extended autoantibody profile, we were able to show that serologic status of SSc patients provides important clues to disease manifestation, co-morbidities and complications. Line blot was a reliable technique to detect autoantibodies in SSc and detected rarer autoantibodies in 42% of our patients. Frontiers Media S.A. 2023-01-04 /pmc/articles/PMC9846214/ /pubmed/36685532 http://dx.doi.org/10.3389/fimmu.2022.1045523 Text en Copyright © 2023 Höppner, Tabeling, Casteleyn, Kedor, Windisch, Burmester, Huscher and Siegert https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Höppner, Jakob Tabeling, Christoph Casteleyn, Vincent Kedor, Claudia Windisch, Wolfram Burmester, Gerd Rüdiger Huscher, Dörte Siegert, Elise Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis |
title | Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis |
title_full | Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis |
title_fullStr | Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis |
title_full_unstemmed | Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis |
title_short | Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis |
title_sort | comprehensive autoantibody profiles in systemic sclerosis: clinical cluster analysis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846214/ https://www.ncbi.nlm.nih.gov/pubmed/36685532 http://dx.doi.org/10.3389/fimmu.2022.1045523 |
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