Greater prevalence of seropositivity for anti-cyclic citrullinated peptide antibody in unaffected first-degree relatives in multicase rheumatoid arthritis-affected families

BACKGROUND/AIMS This study determined the prevalence and determinants of seropositivity for rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and anti-mutated citrullinated vimentin (anti-MCV) antibody in unaffected first-degree relatives (FDRs) of rheumatoid arthritis (RA) patients. METHODS A total of 337 subjects (135 with RA and 202 FDRs) were enrolled in this case-control study. Serum RF, anti-CCP antibody, and anti-MCV antibody were assayed. Subjects in multicase families (≥ 2 affected FDRs within the same family) were identified. Multivariate logistic regression analysis was used to identify risk factors associated with RA-related autoantibodies. RESULTS Seropositivity for RF, anti-CCP antibody, or anti-MCV antibody was detected in 14.4%, 5.0%, or 13.4% of unaffected FDRs, respectively. Anti-CCP antibody seropositivity was more prevalent in FDRs in multicase families (17.8%) than in those not in multicase families (1.3%, p < 0.0001). Significant correlations between RA-associated autoantibodies were detected in the FDR group (between RF and anti-CCP antibody: r = 0.366, p < 0.0001; between RF and anti-MCV antibody: r = 0.343, p < 0.0001; and between anti-CCP antibody and anti-MCV antibody: r = 0.849, p < 0.0001). After adjustment for age and sex, anti-CCP antibody seropositivity in FDRs was significantly associated with being in a multicase family (odds ratio, 49.8; 95% confidence interval, 5.6 to 441.6). CONCLUSIONS The association between anti-CCP antibody seropositivity in unaffected FDRs and being in a multicase family suggests that genetic and/or environmental factors may increase the risk for RA development in unaffected FDRs.