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Current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis
Epidemiological findings suggest a potential role for anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) pathogenesis. ACPA-positive RA is associated with unique genetical and environmental risk factors, in contrast to seronegative RA. ACPA-positive healthy individuals are at...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006837/ https://www.ncbi.nlm.nih.gov/pubmed/33771834 http://dx.doi.org/10.1136/rmdopen-2020-001228 |
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author | Catrina, Anca Krishnamurthy, Akilan Rethi, Bence |
author_facet | Catrina, Anca Krishnamurthy, Akilan Rethi, Bence |
author_sort | Catrina, Anca |
collection | PubMed |
description | Epidemiological findings suggest a potential role for anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) pathogenesis. ACPA-positive RA is associated with unique genetical and environmental risk factors, in contrast to seronegative RA. ACPA-positive healthy individuals are at risk of developing RA and can develop joint pain and bone loss already before disease onset. ACPA injection triggered bone loss and pain-like behaviour in mice and, in the presence of additional arthritis inducers, exacerbated joint inflammation. In cell culture experiments, ACPAs could bind to and modulate a variety of cellular targets, such as macrophages, osteoclasts, synovial fibroblasts, neutrophil granulocytes, mast cells, dendritic cells and platelets, further underlying a potential role for these autoantibodies in triggering pathogenic pathways and providing clues for their mechanisms of action. Patient-derived ACPA clones have been characterised by unique cellular effects and multiple ways to act on the target cells. ACPAs might directly induce stimulatory signals by ligating key citrullinated cell surface molecules or, alternatively, act as immune complexes on Fc receptors and potentially other molecules that recognise carbohydrate moieties. On the contrary to experimentally manufactured ACPA clones, patient-derived ACPAs are highly promiscuous and cross-reactive, suggesting a simultaneous binding to a range of functionally relevant and irrelevant targets. Moreover, several ACPA clones recognise carbamylated or acetylated targets as well. These features complicate the identification and description of ACPA-induced pathogenic mechanisms. In the current review, we summarise recent data on the functional properties of patient-derived ACPAs and present mechanistic models on how these antibodies might contribute to RA pathogenesis. |
format | Online Article Text |
id | pubmed-8006837 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-80068372021-04-16 Current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis Catrina, Anca Krishnamurthy, Akilan Rethi, Bence RMD Open Rheumatoid Arthritis Epidemiological findings suggest a potential role for anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) pathogenesis. ACPA-positive RA is associated with unique genetical and environmental risk factors, in contrast to seronegative RA. ACPA-positive healthy individuals are at risk of developing RA and can develop joint pain and bone loss already before disease onset. ACPA injection triggered bone loss and pain-like behaviour in mice and, in the presence of additional arthritis inducers, exacerbated joint inflammation. In cell culture experiments, ACPAs could bind to and modulate a variety of cellular targets, such as macrophages, osteoclasts, synovial fibroblasts, neutrophil granulocytes, mast cells, dendritic cells and platelets, further underlying a potential role for these autoantibodies in triggering pathogenic pathways and providing clues for their mechanisms of action. Patient-derived ACPA clones have been characterised by unique cellular effects and multiple ways to act on the target cells. ACPAs might directly induce stimulatory signals by ligating key citrullinated cell surface molecules or, alternatively, act as immune complexes on Fc receptors and potentially other molecules that recognise carbohydrate moieties. On the contrary to experimentally manufactured ACPA clones, patient-derived ACPAs are highly promiscuous and cross-reactive, suggesting a simultaneous binding to a range of functionally relevant and irrelevant targets. Moreover, several ACPA clones recognise carbamylated or acetylated targets as well. These features complicate the identification and description of ACPA-induced pathogenic mechanisms. In the current review, we summarise recent data on the functional properties of patient-derived ACPAs and present mechanistic models on how these antibodies might contribute to RA pathogenesis. BMJ Publishing Group 2021-03-26 /pmc/articles/PMC8006837/ /pubmed/33771834 http://dx.doi.org/10.1136/rmdopen-2020-001228 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Rheumatoid Arthritis Catrina, Anca Krishnamurthy, Akilan Rethi, Bence Current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis |
title | Current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis |
title_full | Current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis |
title_fullStr | Current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis |
title_full_unstemmed | Current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis |
title_short | Current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis |
title_sort | current view on the pathogenic role of anti-citrullinated protein antibodies in rheumatoid arthritis |
topic | Rheumatoid Arthritis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006837/ https://www.ncbi.nlm.nih.gov/pubmed/33771834 http://dx.doi.org/10.1136/rmdopen-2020-001228 |
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