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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 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. [ABSTRACT FROM AUTHOR]

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.

Objective. To assess frequency of immunogenetic (HLA-DRB I allels) and immunologic - anti-cyclic citrullinated peptide antibodies (ACCP), IgM rheumatoid factor (RF) - parameters and their significance as markers of early rheumatoid arthritis (RA). Material and methods. HLA-DRB 1 alleles, ACCP and IgM RF were evaluated in 95 pts with early RA who fulfilled ACR criteria 1987 with disease duration 2 years or less. In 85,3% of them disease duration was

Rheumatoid arthritis (RA) is a chronic, destructive autoimmune disease affecting the joints. With more sophisticated and effective therapies becoming available and with the understanding that early intervention is crucial in preventing irreversible joint damage, it is more and more important to diagnose RA at a very early stage in the disease. To facilitate diagnosis during the early stages of the disease, when often not all clinical symptoms are manifest, a good serological marker is needed. Antibodies directed to citrullinated proteins provide this ability. The most sensitive assay to detect these antibodies is the so-called anti-cyclic citrullinated peptide (CCP) enzyme-linked immunosorbent assay (ELISA) assay. In this review, the diagnostic and prognostic potential and the general utility in clinical practice of anti-CCP antibodies are discussed. Furthermore, we elaborate on the mechanisms involved in the generation of citrullinated autoantigens and the possible role of the anti-CCP antibodies and their antigens in the disease. [Copyright &y& Elsevier]