Peptidylarginine deiminase 4 (PADI4) identified as a conformation‐dependent autoantigen in rheumatoid arthritis

Abstract

OBJECTIVE: Peptidylarginine deiminase (PADI) catalyses the post-translational modification of arginine to citrulline, which is specifically recognized by sera from rheumatoid arthritis (RA) patients. The PADI4 gene has recently been identified as a risk factor for RA. We aimed to determine whether PADI4 constitutes an autoantigen in RA. METHODS: Serum samples were obtained from 42 patients with RA, 19 patients with systemic lupus erythematosus (SLE), 23 patients with other rheumatic diseases, and 40 normal individuals. The presence of antibodies against recombinant human PADI4 (anti-PADI4) was examined using enzyme-linked immunosorbent assay (ELISA) and Western blotting. RESULTS: For ELISA, the prevalence of anti-PADI4 among RA patients (50%) was significantly higher than that of normal individuals (2.5%), SLE (10.5%), and other rheumatic diseases (4.3%), while for Western blot analysis, PADI4 was recognized only by a portion of the ELISA-positive serum samples. CONCLUSIONS: PADI4 is an autoantigen in some RA patients, and its conformational epitope(s) may be important.