Antibodies against cyclic citrullinated peptide are associated with HLA-DR4 in simplex and multiplex polyarticular-onset juvenile rheumatoid arthritis

Abstract

AbstractObjectiveAnti–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.MethodsStored 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.ResultsThirteen 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.ConclusionThese 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.

Key Biomarkers

Symptom Clusters