Journal article
Antibodies to Citrullinated Protein Antigens, Rheumatoid Factor Isotypes and the Shared Epitope and the Near-Term Development of Clinically-Apparent Rheumatoid Arthritis
Frontiers in immunology, Vol.13, p.916277
06/22/2022
DOI: 10.3389/fimmu.2022.916277
PMCID: PMC9265214
PMID: 35812446
Abstract
Background/PurposeIn 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 MethodsWe 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). ResultsTwenty-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. ConclusionThese 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.
Details
- Title: Subtitle
- Antibodies to Citrullinated Protein Antigens, Rheumatoid Factor Isotypes and the Shared Epitope and the Near-Term Development of Clinically-Apparent Rheumatoid Arthritis
- Creators
- Dylan T. Bergstedt - University of Colorado Anschutz Medical CampusWyatt J. Tarter - Colorado School of Public HealthRyan A. Peterson - Colorado School of Public HealthMarie L. Feser - University of Colorado Anschutz Medical CampusMark C. Parish - University of Colorado Anschutz Medical CampusChristopher C. Striebich - University of Colorado Anschutz Medical CampusM. Kristen Demoruelle - University of Colorado Anschutz Medical CampusLauraKay Moss - University of Colorado Anschutz Medical CampusElizabeth A. Bemis - University of Colorado Anschutz Medical CampusJill M. Norris - Colorado School of Public HealthV. Michael Holers - University of Colorado Anschutz Medical CampusJess D. Edison - Walter Reed National Military Medical CenterGeoffrey M. Thiele - University of Nebraska Medical CenterTed R. Mikuls - University of Nebraska Medical CenterKevin D. Deane - University of Colorado Anschutz Medical Campus
- Resource Type
- Journal article
- Publication Details
- Frontiers in immunology, Vol.13, p.916277
- DOI
- 10.3389/fimmu.2022.916277
- PMID
- 35812446
- PMCID
- PMC9265214
- NLM abbreviation
- Front Immunol
- ISSN
- 1664-3224
- eISSN
- 1664-3224
- Publisher
- Frontiers Media Sa
- Number of pages
- 10
- Language
- English
- Date published
- 06/22/2022
- Academic Unit
- Biostatistics; Internal Medicine
- Record Identifier
- 9984914150202771
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