combination of autoantibodies to cyclic citrullinated peptide [CCP] and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis

ABSTRACT

Antibodies against cyclic citrullinated peptide [CCP] and rheumatoid factors [RFs] have been demonstrated to predate the onset of rheumatoid arthritis [RA] by months or years. A nested case- control study was performed to analyse the presence of shared epitope [SE] genes, defined as HLA-DRB1-0404 or DRBI-0401, and of anti-CCP antibodies and RFs in individuals who subsequently developed RA. Patients with RA were identified months before the onset of symptoms. Patients have family history of rheumatoid arthritis and recurrent arthralgia. Controls matched for age, sex, and date of sampling were selected randomly from the same cohort. The SE genes were identified by polymerase chain reaction sequence-specific primers. Anti-CCP2 antibodies and RFs were determined using enzyme immunoassays. Fifty-nine individuals with RA were identified, with a median antedating time of 6 months before presenting with symptoms of RA. The sensitivity for SE as a diagnostic indicator for RA was 60% and the specificity was 64%. The corresponding figures for anti-CCP antibodies were 37% and 98%, and for RFs, 17-42% and 94%, respectively. In a logistic regression analysis, SE [odds ratio [OR] = 2.35], anti-CCP antibodies [OR 15.9], and IgA-RF [OR 6.8] significantly predicted RA. In a combination model analysis, anti-CCP antibodies combined with SE had the highest OR [66.8, 95% confidence interval 8.3-539.4] in predicting RA, compared with anti-CCP antibodies without SE [OR = 25.01, 95% confidence interval 2.8-222.2] or SE without anti-CCP antibodies [OR 1.9, 95% confidence interval 0.9-4.2]. This study showed that the presence of anti-CCP antibodies together with SE gene carriage is associated with a very high relative risk for future development of RA