RESEARCH - Independent associations of anti-CCP and RF with radiographic severity of RA

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Research article

Independent associations of anti-cyclical citrullinated peptide antibodies

and rheumatoid factor with radiographic severity of rheumatoid arthritis

Devesh Mewar , bel Coote , J , Ioanna Marinou , Jodie

Keyworth , n C Dickson , Doug S Montgomery , H Binks and

G

Arthritis Research & Therapy 2006, 8:R128

Published 20 July 2006

Several recent publications have established a strong association of

anti-CCP positive RA with carriage of shared epitope alleles. Although

anti-CCP antibodies have also been associated with more severe RA, the issue

of whether this is independent of rheumatoid factor has not been

demonstrated. To determine associations between RF, anti-CCP antibodies, SE

status and radiological damage we studied a large cross-sectional cohort

with longstanding rheumatoid arthritis. Subjects (n=872) enrolled in the

study all fulfilled the ACR criteria for RA, had minimum disease duration of

3 years, and at least one definite radiographic erosion was present in hands

or feet. Radiographs were scored blind at study entry by a single

musculoskeletal radiologist using a modified Larsens score. Anti-CCP

antibody and RF levels were determined by ELISA and DRB1 typing was

performed using PCR-based methodology. Both anti-CCP and RF were strongly

associated with radiographic severity (P<0.0001). In subgroups stratified

for both anti-CCP and RF status evidence of independent associations of both

antibodies with radiographic outcome were found (P<0.0001). An association

of SE alleles with radiographic severity was present only in RF negative

subjects. Anti-CCP positivity was associated with SE status with evidence of

a gene-dose effect, most markedly in RF negative individuals (P<0.01).

Anti-CCP and RF are independent severity factors for RA, with SE alleles

playing at most a secondary role. Our data support the view that previously

described associations between SE and radiological severity especially in

RF- patients may be indirect and due to an association with anti-CCP.

http://arthritis-research.com/content/8/4/R128/abstract

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