The Journal of Rheumatology grants from the National Natural Science Foundation of China (30430290, 30671933) and National 863 key project

ABSTRACT. Objective. To detect anti-peptidylarginine deiminase 4 (PAD4) antibody in patients with rheumatoid arthritis (RA) and to investigate its clinical significance in the pathogenesis of RA. Methods. Serum samples were obtained from 109 patients with RA, 67 systemic lupus erythematosus (SLE), 48 primary Sjögren's syndrome (pSS), 41 systemic sclerosis (SSc), 34 osteoarthritis (OA), 23 dermatomyositis/polymyositis (DM/PM), and 19 ankylosing spondylitis (AS) and 106 healthy individuals. The presence of antibodies against recombinant human PAD4 (anti-PAD4) was examined by ELISA. Associations between anti-PAD4 and the clinical features of RA were evaluated. Results. The prevalence of anti-PAD4 in RA patients (45.0%) was significantly higher than those of SLE (9.0%), pSS (4.2%), SSc (9.8%), OA (5.9%), DM/PM (13.0%), AS (0%), and controls (4.7%). The mean titer of anti-PAD4 in RA was also significantly higher than in SLE, other rheumatic diseases, and controls. Disease Activity Score-28 (DAS28), anti-cyclic citrullinated peptide (CCP) antibody, erythrocyte sedimentation rate, rheumatoid factor, IgM, and IgG in anti-PAD4-positive patients were all higher than in anti-PAD4-negative patients. There were positive correlations between anti-PAD4 and DAS28 score (r = 0.333, p < 0.01) and anti-CCP antibody (r = 0.248, p < 0.05). Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints that eventually leads to erosive changes and dysfunction. Antibodies against citrulline-containing epitopes such as antiperinuclear factor, antikeratin antibodies (AKA), antifilaggrin antibodies, and anti-cyclic citrullinated peptide (CCP) antibodies are very specific in RA 1-4 . Citrulline is formed by posttranslational modification of arginine residues by an enzyme named peptidylarginine deiminase (PAD). Five different isotypes of PAD have been identified in humans, including PAD1, PAD2, PAD3, PAD4, and PAD6 5 . In 2003, Suzuki, et al used a case-control linkage disequilibrium study to show that the gene of PADI4 is a susceptibility locus for RA and has correlation with production of anti-CCP antibody 6 , indicating that PADI4 may play a role in the pathogenesis of RA. But little is known about how PADI4 is involved in the development of RA. Recently, Takizawa, et al found that sera from RA patients recognized recombinant human PAD4 using an enzyme-linked immunosorbent assay (ELISA), which implies that PAD4 acts as an autoantigen in RA 7 . However, in that study, only 42 patients with RA were tested, and no further analysis of association between anti-PAD4 and other disease features was assessed. We determined the prevalence of anti-PAD4 in a large cohort of Chinese patients with RA and other rheumatic diseases by ELISA, and investigated the associations between anti-PAD4 and the clinical and laboratory features of RA. Conclusion. MATERIALS AND METHOD