Antibodies against cyclic citrullinated peptide are associated with HLA-DR4 in simplex and multiplex polyarticular-onset juvenile rheumatoid arthritis.
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.
Ferucci
Elizabeth D
ED
Division of Rheumatology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
Majka
Darcy S
DS
Parrish
Lezlie A
LA
Moroldo
Marta B
MB
Ryan
Mary
M
Passo
Murray
M
Thompson
Susan D
SD
Deane
Kevin D
KD
Rewers
Marian
M
Arend
William P
WP
Glass
David N
DN
Norris
Jill M
JM
Holers
V Michael
VM
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
D000906:Antibodies; D001323:Autoantibodies; D015804:HLA-DR4 Antigen; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor