Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Catrina, Anca, Krishnamurthy, Akilan, Rethi, Bence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
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
_version_ 1783672378731003904
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
work_keys_str_mv AT catrinaanca currentviewonthepathogenicroleofanticitrullinatedproteinantibodiesinrheumatoidarthritis
AT krishnamurthyakilan currentviewonthepathogenicroleofanticitrullinatedproteinantibodiesinrheumatoidarthritis
AT rethibence currentviewonthepathogenicroleofanticitrullinatedproteinantibodiesinrheumatoidarthritis