Antibodies against cyclic citrullinated peptide are associated with the DRB1 shared epitope and predict joint erosion in rheumatoid arthritis.
OBJECTIVE
To evaluate antibodies against cyclic citrullinated peptide (anti-CCP antibodies) for their predictive value for severe joint destruction in rheumatoid arthritis (RA) and to examine their relationship to shared epitope (SE)-positive DRB1 alleles.


METHODS
Concentrations of anti-CCP antibodies were determined in sera from 126 patients with recent onset RA who had been followed prospectively for 6 yr. Progression of joint destruction was evaluated according to Larsen by scoring radiographs from the hand and feet taken at baseline and after 1, 2, 4 and 6 yr of observation. In addition to clinical parameters, the presence of SE-positive DRB1 alleles and of rheumatoid factor IgM and IgA was determined.


RESULTS
Anti-CCP antibodies were found more frequently and in higher concentrations in both DRB1*01-positive and in DRB1*04-positive SE-positive patients compared with SE-negative patients. Severe joint destruction as defined by a Larsen score in the upper third of the study population was predicted by positivity for anti-CCP antibodies, by the presence of SE-positive DRB1*04 alleles and by the presence of erosive disease at initial presentation. Multiple logistic regression analysis revealed that SE-positive DRB1*04 alleles and anti-CCP antibodies exerted a significant influence on the progression of joint destruction.


CONCLUSIONS
The association of anti-CCP antibodies with DRB1*01 and with SE-positive DRB1*04 alleles implies a functional role for the SE sequence motif. The determination of SE-positive DRB1*04 alleles and of anti-CCP antibody positivity facilitates the prediction of disease course and prognosis at the time of initial presentation.
Kaltenhäuser
S
S
Department of Medicine IV, University of Leipzig, Liebigstrasse 22, 04103 Leipzig, Germany.
Pierer
M
M
Arnold
S
S
Kamprad
M
M
Baerwald
C
C
Häntzschel
H
H
Wagner
U
U
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D000939:Epitopes / Q000235:genetics; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011379:Prognosis; D011446:Prospective Studies; D011859:Radiography
D001323:Autoantibodies; D015415:Biomarkers; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide