Antibodies against cyclic citrullinated peptide are associated with HLA–DR4 in simplex and multiplex polyarticular-onset juvenile rheumatoid arthritis
Article first published online: 7 JAN 2005
Copyright © 2005 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 52, Issue 1, pages 239–246, January 2005
How to Cite
Ferucci, E. D., Majka, D. S., Parrish, L. A., Moroldo, M. B., Ryan, M., Passo, M., Thompson, S. D., Deane, K. D., Rewers, M., Arend, W. P., Glass, D. N., Norris, J. M. and Holers, V. M. (2005), Antibodies against cyclic citrullinated peptide are associated with HLA–DR4 in simplex and multiplex polyarticular-onset juvenile rheumatoid arthritis. Arthritis & Rheumatism, 52: 239–246. doi: 10.1002/art.20773
- Issue published online: 7 JAN 2005
- Article first published online: 7 JAN 2005
- Manuscript Accepted: 12 OCT 2004
- Manuscript Received: 4 JUN 2004
- NIH. Grant Numbers: U19-AI-50864, T32-AR-07534, N01-AR-42218, P60-AR-47784, P30-AR-47363, R01-DK-32493
- Smyth Professorship in Rheumatology
Anti–cyclic citrullinated peptide (anti-CCP) antibodies have been detected in patients with juvenile rheumatoid arthritis (JRA), particularly in those with polyarticular, rheumatoid factor (RF)-positive JRA. Our objectives were to determine whether anti-CCP antibodies are associated with HLA–DR4 in children with polyarticular JRA, whether anti-CCP antibodies are associated with clinical features of disease, and whether affected sibling pairs (ASPs) with JRA are concordant for this antibody.
Stored serum samples obtained from 230 HLA-typed patients with JRA (77 with polyarticular-onset disease and 153 with pauciarticular- or systemic-onset disease), 100 JRA ASPs, and 688 healthy children were tested for anti-CCP antibodies and RF.
Thirteen percent of the patients with polyarticular-onset JRA and 2% of the other JRA patients exhibited anti-CCP antibodies, compared with only 0.6% of the controls. Fifty-seven percent of RF-positive patients with polyarticular-onset JRA had anti-CCP antibodies. HLA–DR4–positive patients with polyarticular-onset JRA were more likely to have anti-CCP antibodies than were those without HLA–DR4 alleles (odds ratio [OR] 5.20, 95% confidence interval [95% CI] 1.30–20.9). Anti-CCP antibodies were associated with polyarticular onset (OR 7.46, 95% CI 1.99–28.0), a polyarticular disease course (OR 9.78, 95% CI 1.25–76.7), and erosive disease (OR 14.3, 95% CI 3.01–67.9). Concordance rates for anti-CCP antibodies among ASPs were statistically significant.
These data demonstrate increased anti-CCP antibody formation in HLA–DR4–positive patients with polyarticular-onset JRA. The overall prevalence of anti-CCP antibodies in JRA is low, but a substantial proportion of RF-positive patients with polyarticular-onset JRA have these antibodies. Anti-CCP antibodies in JRA are associated with polyarticular onset, a polyarticular course, and erosive disease.