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Logo of arthrestherBioMed Centralbiomed central web sitesearchsubmit a manuscriptregisterthis articleArthritis Research & Therapy
 
Arthritis Res Ther. 2006; 8(4): R128.
Published online Jul 20, 2006. doi:  10.1186/ar2017
PMCID: PMC1779371
Independent associations of anti-cyclic citrullinated peptide antibodies and rheumatoid factor with radiographic severity of rheumatoid arthritis
Devesh Mewar,1 Annabel Coote,1 David J Moore,1 Ioanna Marinou,1 Jodie Keyworth,1 Marion C Dickson,2 Doug S Montgomery,2 Michael H Binks,2 and Anthony G Wilsoncorresponding author1
1Division of Genomic Medicine, University of Sheffield, Sheffield, UK
2GlaxoSmithKline R&D, Stevenage, UK
corresponding authorCorresponding author.
Devesh Mewar: d.mewar/at/shef.ac.uk; Annabel Coote: annabelcoote/at/hotmail.com; David J Moore: david.moore/at/sth.nhs.uk; Ioanna Marinou: mdp04im/at/shef.ac.uk; Jodie Keyworth: j.keyworth/at/shef.ac.uk; Marion C Dickson: marion.c.dickson/at/gsk.com; Doug S Montgomery: doug.s.montgomery/at/gsk.com; Michael H Binks: michael.h.binks/at/gsk.com; Anthony G Wilson: a.g.wilson/at/shef.ac.uk
Received May 26, 2006; Revisions requested June 27, 2006; Revised July 7, 2006; Accepted July 20, 2006.
Abstract
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.
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