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

Arthritis Rheum. 2005 Jan;52(1):239-46. doi: 10.1002/art.20773.


Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Alleles
  • Antibodies / blood*
  • Arthritis, Juvenile / genetics
  • Arthritis, Juvenile / immunology*
  • Arthritis, Juvenile / physiopathology
  • Autoantibodies / blood
  • Case-Control Studies
  • Child
  • Female
  • HLA-DR4 Antigen / blood*
  • HLA-DR4 Antigen / genetics
  • Humans
  • Male
  • Peptides, Cyclic / immunology*
  • Rheumatoid Factor / blood
  • Siblings


  • Antibodies
  • Autoantibodies
  • HLA-DR4 Antigen
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Rheumatoid Factor