title: Independent associations of anti-cyclic citrullinated peptide antibodies and rheumatoid factor with radiographic severity of rheumatoid arthritis.
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.
authors.affiliation: Division of Genomic Medicine, University of Sheffield, Sheffield, UK.
authors.forename: Devesh
authors.initials: D
authors.lastname: Mewar
authors.forename: Annabel
authors.initials: A
authors.lastname: Coote
authors.forename: David J
authors.initials: DJ
authors.lastname: Moore
authors.forename: Ioanna
authors.initials: I
authors.lastname: Marinou
authors.forename: Jodie
authors.initials: J
authors.lastname: Keyworth
authors.forename: Marion C
authors.initials: MC
authors.lastname: Dickson
authors.forename: Doug S
authors.initials: DS
authors.lastname: Montgomery
authors.forename: Michael H
authors.initials: MH
authors.lastname: Binks
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Wilson
mesh_terms: D000483:Alleles; D000906:Antibodies / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000000981:diagnostic imaging* / Q000276:immunology; D001175:Arthrography; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D012217:Rheumatoid Factor / Q000097:blood*; D012720:Severity of Illness Index
chemical_list: D000906:Antibodies; D000939:Epitopes; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor