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Antibodies to Citrullinated Protein Antigens, Rheumatoid Factor Isotypes and the Shared Epitope and the Near-Term Development of Clinically-Apparent Rheumatoid Arthritis
BACKGROUND/PURPOSE: In rheumatoid arthritis (RA) autoantibodies including antibodies to citrullinated protein antigens (ACPA) and rheumatoid factor (RF) can be predictive of incident clinical RA. However, there is limited understanding of how antibody changes over time impact prediction of the likel...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265214/ https://www.ncbi.nlm.nih.gov/pubmed/35812446 http://dx.doi.org/10.3389/fimmu.2022.916277 |
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author | Bergstedt, Dylan T. Tarter, Wyatt J. Peterson, Ryan A. Feser, Marie L. Parish, Mark C. Striebich, Christopher C. Demoruelle, M. Kristen Moss, LauraKay Bemis, Elizabeth A. Norris, Jill M. Holers, V. Michael Edison, Jess D. Thiele, Geoffrey M. Mikuls, Ted R. Deane, Kevin D. |
author_facet | Bergstedt, Dylan T. Tarter, Wyatt J. Peterson, Ryan A. Feser, Marie L. Parish, Mark C. Striebich, Christopher C. Demoruelle, M. Kristen Moss, LauraKay Bemis, Elizabeth A. Norris, Jill M. Holers, V. Michael Edison, Jess D. Thiele, Geoffrey M. Mikuls, Ted R. Deane, Kevin D. |
author_sort | Bergstedt, Dylan T. |
collection | PubMed |
description | BACKGROUND/PURPOSE: In rheumatoid arthritis (RA) autoantibodies including antibodies to citrullinated protein antigens (ACPA) and rheumatoid factor (RF) can be predictive of incident clinical RA. However, there is limited understanding of how antibody changes over time impact prediction of the likelihood and timing of future clinical RA. MATERIALS AND METHODS: We evaluated relationships between ACPA, the shared epitope (SE), RF isotypes and incident RA in a prospective cohort of 90 ACPA(+) individuals without baseline arthritis identified through health-fair testing (i.e. Healthfair). We also evaluated ACPA and RF isotypes and time-to-diagnosis of RA in a retrospective cohort of 215 individuals with RA from the Department of Defense Serum Repository (DoDSR). RESULTS: Twenty-six of 90 (29%) of ACPA(+) Healthfair participants developed incident RA. Baseline or incident dual RF-IgA and RF-IgM positivity was associated with increased risk for incident RA (HR 3.09; 95% CI 1.15 to 8.29) although RFs were negative in ~50% of individuals with incident RA. SE was associated with increased risk of RA (HR 2.87, 95% CI 1.22-6.76). In the DoDSR cohort, triple positivity for ACPA, RF-IgA and RF-IgM was present a median of 1-2 years prior to RA diagnosis, with some sex-specific differences. CONCLUSION: These findings can be used to counsel individuals at-risk for future RA and to design clinical trials for RA prevention. The findings also suggest that RF could be a surrogate outcome as a success of an immunologic intervention in RA prevention. Additional studies are needed to understand the biologic of different patterns of autoantibody elevations in RA evolution. |
format | Online Article Text |
id | pubmed-9265214 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92652142022-07-09 Antibodies to Citrullinated Protein Antigens, Rheumatoid Factor Isotypes and the Shared Epitope and the Near-Term Development of Clinically-Apparent Rheumatoid Arthritis Bergstedt, Dylan T. Tarter, Wyatt J. Peterson, Ryan A. Feser, Marie L. Parish, Mark C. Striebich, Christopher C. Demoruelle, M. Kristen Moss, LauraKay Bemis, Elizabeth A. Norris, Jill M. Holers, V. Michael Edison, Jess D. Thiele, Geoffrey M. Mikuls, Ted R. Deane, Kevin D. Front Immunol Immunology BACKGROUND/PURPOSE: In rheumatoid arthritis (RA) autoantibodies including antibodies to citrullinated protein antigens (ACPA) and rheumatoid factor (RF) can be predictive of incident clinical RA. However, there is limited understanding of how antibody changes over time impact prediction of the likelihood and timing of future clinical RA. MATERIALS AND METHODS: We evaluated relationships between ACPA, the shared epitope (SE), RF isotypes and incident RA in a prospective cohort of 90 ACPA(+) individuals without baseline arthritis identified through health-fair testing (i.e. Healthfair). We also evaluated ACPA and RF isotypes and time-to-diagnosis of RA in a retrospective cohort of 215 individuals with RA from the Department of Defense Serum Repository (DoDSR). RESULTS: Twenty-six of 90 (29%) of ACPA(+) Healthfair participants developed incident RA. Baseline or incident dual RF-IgA and RF-IgM positivity was associated with increased risk for incident RA (HR 3.09; 95% CI 1.15 to 8.29) although RFs were negative in ~50% of individuals with incident RA. SE was associated with increased risk of RA (HR 2.87, 95% CI 1.22-6.76). In the DoDSR cohort, triple positivity for ACPA, RF-IgA and RF-IgM was present a median of 1-2 years prior to RA diagnosis, with some sex-specific differences. CONCLUSION: These findings can be used to counsel individuals at-risk for future RA and to design clinical trials for RA prevention. The findings also suggest that RF could be a surrogate outcome as a success of an immunologic intervention in RA prevention. Additional studies are needed to understand the biologic of different patterns of autoantibody elevations in RA evolution. Frontiers Media S.A. 2022-06-22 /pmc/articles/PMC9265214/ /pubmed/35812446 http://dx.doi.org/10.3389/fimmu.2022.916277 Text en Copyright © 2022 Bergstedt, Tarter, Peterson, Feser, Parish, Striebich, Demoruelle, Moss, Bemis, Norris, Holers, Edison, Thiele, Mikuls and Deane 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 Bergstedt, Dylan T. Tarter, Wyatt J. Peterson, Ryan A. Feser, Marie L. Parish, Mark C. Striebich, Christopher C. Demoruelle, M. Kristen Moss, LauraKay Bemis, Elizabeth A. Norris, Jill M. Holers, V. Michael Edison, Jess D. Thiele, Geoffrey M. Mikuls, Ted R. Deane, Kevin D. Antibodies to Citrullinated Protein Antigens, Rheumatoid Factor Isotypes and the Shared Epitope and the Near-Term Development of Clinically-Apparent Rheumatoid Arthritis |
title | Antibodies to Citrullinated Protein Antigens, Rheumatoid Factor Isotypes and the Shared Epitope and the Near-Term Development of Clinically-Apparent Rheumatoid Arthritis |
title_full | Antibodies to Citrullinated Protein Antigens, Rheumatoid Factor Isotypes and the Shared Epitope and the Near-Term Development of Clinically-Apparent Rheumatoid Arthritis |
title_fullStr | Antibodies to Citrullinated Protein Antigens, Rheumatoid Factor Isotypes and the Shared Epitope and the Near-Term Development of Clinically-Apparent Rheumatoid Arthritis |
title_full_unstemmed | Antibodies to Citrullinated Protein Antigens, Rheumatoid Factor Isotypes and the Shared Epitope and the Near-Term Development of Clinically-Apparent Rheumatoid Arthritis |
title_short | Antibodies to Citrullinated Protein Antigens, Rheumatoid Factor Isotypes and the Shared Epitope and the Near-Term Development of Clinically-Apparent Rheumatoid Arthritis |
title_sort | antibodies to citrullinated protein antigens, rheumatoid factor isotypes and the shared epitope and the near-term development of clinically-apparent rheumatoid arthritis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265214/ https://www.ncbi.nlm.nih.gov/pubmed/35812446 http://dx.doi.org/10.3389/fimmu.2022.916277 |
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