Mewar, D., Coote, A., Moore, D.J., Marinou, I., Keyworth, J., Dickson, M.C., Montgomery, D.S., Binks, M.H. and Wilson, A.G. (2006) Independent associations of anti-cyclic citrullinated peptide antibodies and rheumatoid factor with radiographic severity of rheumatoid arthritis. Arthritis Research & Therapy, 8 (4). R128. ISSN 1478-6354
Several recent publications have established a strong association between anti-cyclic citrullinated peptide antibody (anti-CCP)-positive rheumatoid arthritis (RA) and carriage of shared epitope (SE) alleles. Although anti-CCP have also been associated with more severe RA, the issue of whether this is independent of rheumatoid factor (RF) has not been addressed. To identify associations between RF, anti-CCP, SE status and radiological damage, we studied a large cross-sectional cohort with longstanding RA. Individuals (n = 872) enrolled in the study all fulfilled the American College of Rheumatology criteria for RA, had a 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 Larsen's score. Anti-CCP and RF levels were determined using enzyme-linked immunosorbent assay, and DRB1 typing was performed using polymerase chain reaction based methodology. Both anti-CCP and RF levels 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 was found (P < 0.0001). An association of SE alleles with radiographic severity was present only in RF-negative individuals. 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 status 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-negative patients, may be indirect and due to an association with anti-CCP.
|Copyright, Publisher and Additional Information:||© 2006 Mewar et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.|
|Institution:||The University of Sheffield|
|Academic Units:||The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Division of Genomic Medicine (Sheffield)|
|Depositing User:||Sheffield Import|
|Date Deposited:||09 Oct 2009 09:29|
|Last Modified:||09 Oct 2009 09:29|