Prevalence and Significance of Anti-Peptidylarginine Deiminase 4 Antibodies in Rheumatoid Arthritis

JINXIA ZHAO, YI ZHAO, JING HE, RULIN JIA, and ZHANGUO LI

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).

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. (First Release April 1 2008; J Rheumatol 2008;35:969–74)

Key Indexing Terms:

PEPTIDYLARGININE DEIMINASE  
CITRULLINE
ANTIBODIES
RHEUMATOID ARTHRITIS

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From the Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing, China.

Supported in part by grants from the National Natural Science Foundation of China (30430290, 30671933) and National 863 key project (2006AA02Z4D0).

J. Zhao, MD; Y. Zhao, PhD; J. He, MD; R. Jia, BS, Researcher; Z.G. Li, MD, PhD, Professor, Chief, Department of Rheumatology and Immunology, People's Hospital, Peking University.

Address reprint requests to Prof. Z.G. Li, Department of Rheumatology and Immunology, People's Hospital, Peking University, 11 Xizhimen South St., Beijing, 100044, P.R. China. E-mail: rheumatology2008@yahoo.com.cn

Accepted for publication January 8, 2008.