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).
Conclusion: The presence of anti-PAD4 in RA indicates that PAD4 may act as an autoantigen that may play a role in the pathogenesis of RA.