Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis

Abstract Objective Modification of antigens represents a trigger for the generation of autoantibodies. In the pathogenesis of rheumatoid arthritis (RA), citrullination of proteins has been shown to be a critical process, and the determination of antibodies against citrullinated antigens has been a diagnostic milestone. We undertook this study to determine whether antibodies to mutated and citrullinated vimentin (MCV) could serve as a diagnostic and prognostic marker for RA. Methods We identified novel isoforms of human MCV in the synovial fluid of RA patients. The significance of these disease‐related modifications was investigated by the analysis of autoantibody reactivities. In a group of 1,151 RA patients, the diagnostic significance and the prognostic value of an anti‐MCV enzyme‐linked immunosorbent assay (ELISA) were compared with that of an anti–cyclic citrullinated peptide (anti‐CCP) ELISA. Results In RA, sensitivities of 82% and 72% were calculated for the anti‐MCV and anti‐CCP assays, respectively. The specificity of both assays was comparable (98% and 96%, respectively). In followup analyses of 16 RA patients with moderate disease activity (mean Disease Activity Score in 28 joints [DAS28] of 2.72) and 26 RA patients with active disease (mean DAS28 of 5.07), disease stratification of RA was possible using the anti‐MCV assay ( P = 0.0084). A significant correlation of anti‐MCV antibodies with the DAS28 was documented (r = 0.5334, P = 0.0003), in 42 RA patients (n = 427 antibody determinations at different time points). Conclusion Antigenic properties of vimentin were determined by mutation and citrullination. Anti‐MCV antibodies are a novel diagnostic marker for RA. Furthermore, they may allow monitoring and—if confirmed in even larger series of patients—stratification of disease.