Association of anti-citrullinated vimentin and anti-citrullinated α-enolase antibodies with subsets of rheumatoid arthritis

Objective To determine whether the anticitrullinated vimentin peptide 6075 (antiCit-vimentin) and the immunodominant anticitrullinated a-enolase peptide 1 (antiCEP-1) antibodies are associated with subsets of patients with rheumatoid arthritis (RA) independently of the associations between anticyclic citrullinated peptide (anti-CCP) antibodies and clinical features of RA. Methods The 3 antibody types were quantified by enzyme-linked immunosorbent assay (ELISA) in serum samples from 521 patients with RA and 173 healthy controls of Spanish ancestry. Genotypes for HLADRB1 alleles and rs2476601 in PTPN22 were available for these patients and controls plus an additional 106 healthy controls. A combined analysis of the 3 antibodies was conducted using stratified contingency tables and logistic regression models. Results A differential, particularly strong, and independent association was observed between the presence of antiCit-vimentin antibodies and the presence of shared epitope (SE) alleles, specifically in patients carrying 2 SE alleles, and between the presence of anti Cit-vimentin antibodies and the prevalence of joint erosion. Associations were observed between antiCEP-1 positivity and the presence of HLADRB1 and PTPN22 risk alleles and their additive interaction. These associations were not accounted for by the anti-CCP status. Conclusion Our results indicate that the 2 antibodies against citrullinated peptides analyzed in this study add specific information beyond that obtained with the anti-CCP status. They define subgroups of patients with RA in which genetic factors have different weight and there is an observed difference in the prevalence of erosions.