title: Antibodies against cyclic citrullinated peptide are associated with HLA-DR4 in simplex and multiplex polyarticular-onset juvenile rheumatoid arthritis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Rheumatology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Ferucci
authors.forename: Darcy S
authors.initials: DS
authors.lastname: Majka
authors.forename: Lezlie A
authors.initials: LA
authors.lastname: Parrish
authors.forename: Marta B
authors.initials: MB
authors.lastname: Moroldo
authors.forename: Mary
authors.initials: M
authors.lastname: Ryan
authors.forename: Murray
authors.initials: M
authors.lastname: Passo
authors.forename: Susan D
authors.initials: SD
authors.lastname: Thompson
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Deane
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.forename: William P
authors.initials: WP
authors.lastname: Arend
authors.forename: David N
authors.initials: DN
authors.lastname: Glass
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.forename: V Michael
authors.initials: VM
authors.lastname: Holers
mesh_terms: D000293:Adolescent; D000483:Alleles; D000906:Antibodies / Q000097:blood*; D001171:Arthritis, Juvenile / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D005260:Female; D015804:HLA-DR4 Antigen / Q000097:blood* / Q000235:genetics; D006801:Humans; D008297:Male; D010456:Peptides, Cyclic / Q000276:immunology*; D012217:Rheumatoid Factor / Q000097:blood; D035781:Siblings
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D015804:HLA-DR4 Antigen; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor