Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis

TLDR

The study aimed to assess the prevalence and predictive value of anti‑cyclic citrullinated peptide antibodies and their relationship to rheumatoid factor isotypes in individuals who later developed rheumatoid arthritis, using a nested case‑control design within Swedish cohorts. Researchers identified RA cases among blood donors with pre‑symptom samples and matched controls from the same cohorts, measured anti‑CCP and RF isotypes by enzyme immunoassays, and analyzed 83 RA individuals whose samples were taken a median of 2.5 years before disease onset. In pre‑symptomatic samples, anti‑CCP and IgA‑RF antibodies were present in about one third of future RA patients, with sensitivities rising from 25–29 % >1.5 years to 52–39 % ≤1.5 years before symptoms, and both markers were significant predictors of RA, with anti‑CCP showing the highest predictive value, indicating early citrullination and autoantibody production.

Abstract

To evaluate the prevalence and predictive value of anti-cyclic citrullinated peptide (anti-CCP) antibodies in individuals who subsequently developed rheumatoid arthritis (RA) and to determine the relationship to rheumatoid factor (RF) of any isotype.A case-control study was nested within the Northern Sweden Health and Disease Study and the Maternity cohorts of Northern Sweden. Patients with RA were identified among blood donors whose samples had been taken years before the onset of symptoms. Control subjects matched for age, sex, date of sampling, and residential area were selected randomly from the same cohorts. Anti-CCP antibody and RFs were determined using enzyme immunoassays.Eighty-three individuals with RA were identified as having donated blood before presenting with any symptoms of joint disease (median 2.5 years [interquartile range 1.1-4.7] before RA). In samples obtained before the onset of RA, the prevalence of autoantibodies was 33.7% for anti-CCP, 16.9% for IgG-RF, 19.3% for IgM-RF, and 33.7% for IgA-RF (all highly significant compared with controls). The sensitivities for detecting these autoantibodies >1.5 years and </=1.5 years before the appearance of any RA symptoms were 25% and 52% for anti-CCP, 15% and 30% for IgM-RF, 12% and 27% for IgG-RF, and 29% and 39% for IgA-RF. In conditional logistic regression models, anti-CCP antibody and IgA-RF were found to be significant predictors of RA.Anti-CCP antibody and RFs of all isotypes predated the onset of RA by several years. The presence of anti-CCP and IgA-RF predicted the development of RA, with anti-CCP antibody having the highest predictive value. This indicates that citrullination and the production of anti-CCP and RF autoantibodies are early processes in RA.