title: Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome.
abstract: OBJECTIVE
  Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been identified as highly specific for rheumatoid arthritis (RA). Studies suggest an association with radiographic outcome. The aims of this study were to assess the diagnostic and prognostic utility of the second-generation anti-CCP(2) test in a large cohort of early RA patients compared with connective tissue disease (CTD) controls.
  
  
  METHODS
  One hundred and eighty-two patients with RA and 121 patients with CTD were recruited. All RA patients had less than 24 months of symptoms and had CRP, rheumatoid factor (RF), HLA typing (SE) and anti-CCP(2) antibodies measured at baseline. Function was assessed using the Health Assessment Questionnaire (HAQ) and X-rays performed at 0, 12 and 24 months.
  
  
  RESULTS
  The anti-CCP(2) antibody test demonstrated a specificity of 91% and sensitivity of 81% for RA when compared with controls. In RF-negative patients, specificity was 92% and sensitivity 60%. Baseline demographics of the RA cohort showed mean age 57 yr, mean symptom duration 7 months, 63% RF-positive patients, 72% SE-positive, 81% CCP-positive and 21% erosive. The only predictor of change in Larsen score from 0 to 24 months in the cohort was the presence of the shared epitope (P<0.05) and in the RF-negative subgroup it was CCP(2) antibody titre >100 (P<0.05). Baseline HAQ was the only significant predictor of HAQ at 24 months, but in the RF-negative subgroup CCP(2) antibody titre >100 predicted a poor functional response at 24 months (P<0.05).
  
  
  CONCLUSIONS
  This study confirms the diagnostic utility of anti-CCP(2) antibodies in early RA, particularly in seronegative patients, in whom anti-CCP(2) positivity also conferred prognostic utility for radiographic and functional outcomes.
authors.affiliation: Academic Unit of Musculoskeletal Disease, Department of Rheumatology, Chapel Allerton Hospital, Chapeltown Road, Leeds LS74SA, UK. Mark.Quinn@York.nhs.uk
authors.forename: M A
authors.initials: MA
authors.lastname: Quinn
authors.forename: A K S
authors.initials: AK
authors.lastname: Gough
authors.forename: M J
authors.initials: MJ
authors.lastname: Green
authors.forename: J
authors.initials: J
authors.lastname: Devlin
authors.forename: E M A
authors.initials: EM
authors.lastname: Hensor
authors.forename: A
authors.initials: A
authors.lastname: Greenstein
authors.forename: A
authors.initials: A
authors.lastname: Fraser
authors.forename: P
authors.initials: P
authors.lastname: Emery
mesh_terms: D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis*; D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D004185:Disability Evaluation; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011379:Prognosis; D011859:Radiography; D012217:Rheumatoid Factor / Q000276:immunology; D012680:Sensitivity and Specificity; D013585:Synovitis / Q000175:diagnosis / Q000209:etiology / Q000276:immunology
chemical_list: D001323:Autoantibodies; D006684:HLA-DR Antigens; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002097:C-Reactive Protein; D012217:Rheumatoid Factor