title: Anticarbamylated protein antibodies are associated with long-term disability and increased disease activity in patients with early inflammatory arthritis: results from the Norfolk Arthritis Register.
abstract: Anticarbamylated protein (anti-CarP) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis. The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years' follow-up in a cohort of patients with inflammatory polyarthritis (IP).
  
  
  
  Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009. At baseline, Health Assessment Questionnaire (HAQ) and 28 joint disease activity scores (DAS28) were obtained, and C reactive protein, rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA) and anti-CarP antibodies were measured. Further HAQ scores and DAS28 were obtained at regular intervals over 20 years. Generalised estimating equations were used to test the association between anti-CarP antibody status and longitudinal HAQ and DAS28 scores; adjusting for age, gender, smoking status, year of inclusion and ACPA status. Analyses were repeated in subgroups stratified by ACPA status. The relative association of RF, ACPA and anti-CarP antibodies with HAQ and DAS28 scores was investigated using a random effects model.
  
  
  
  1995 patients were included; 1310 (66%) were female. Anti-CarP antibodies were significantly associated with more disability and higher disease activity, HAQ multivariate β-coefficient (95% CI) 0.12 (0.02 to 0.21), and these associations remained significant in the ACPA-negative subgroups. The associations of RF, ACPA and anti-CarP antibodies were found to be additive in the random effects model.
  
  
  
  Anti-CarP antibodies are associated with increased disability and higher disease activity in patients with IP. Our results suggest that measurement of anti-CarP antibodies may be useful in identifying ACPA-negative patients with worse long-term outcomes. Further, anti-CarP antibody status provided additional information about RF and ACPA.
authors.affiliation: Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, UK.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Humphreys
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marije K
authors.initials: MK
authors.lastname: Verheul
authors.affiliation: Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
authors.affiliation: Arthritis Research UK Centre for Genetics and Genomics, University of Manchester, Manchester, UK.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: MacGregor
authors.affiliation: Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Lunt
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rene Em
authors.initials: RE
authors.lastname: Toes
authors.affiliation: Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, UK NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Deborah Pm
authors.initials: DP
authors.lastname: Symmons
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Leendert A
authors.initials: LA
authors.lastname: Trouw
authors.affiliation: Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, UK.
authors.forename: Suzanne Mm
authors.initials: SM
authors.lastname: Verstappen
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002219:Carbamates / Q000276:immunology*; D004185:Disability Evaluation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D011379:Prognosis; D012042:Registries; D012217:Rheumatoid Factor / Q000097:blood; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D002219:Carbamates; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor
keywords: Autoantibodies; Disease Activity; Early Rheumatoid Arthritis; Epidemiology; Rheumatoid Arthritis