title: The ACPA isotype profile reflects long-term radiographic progression in rheumatoid arthritis.
abstract: BACKGROUND
  The presence of anti-citrullinated protein antibodies (ACPA) is a powerful predictive factor for the development and progression of rheumatoid arthritis (RA). The ACPA response has been shown to consist of various isotypes, but the consequences of differences in isotype distribution have not been extensively investigated.
  
  
  OBJECTIVE
  To investigate the relationship between ACPA isotypes, disease progression and radiological outcome.
  
  
  METHODS
  ACPA isotypes were determined in sera of anti-cyclic citrullinated peptide 2-positive patients by enzyme-linked immunosorbent assay (ELISA). To investigate whether the ACPA response continues to evolve during disease development, the ACPA isotype profile during progression of undifferentiated arthritis (UA) to RA was studied. The association of disease progression with ACPA isotype use was assessed using long-term radiographic follow-up data from patients with RA in two independent cohorts.
  
  
  RESULTS
  The ACPA isotype distribution did not expand during disease progression from UA to RA, but was relatively stable over time. In both RA cohorts, the baseline ACPA isotype profile was a significant predictor of disease severity, with more isotypes indicating a higher risk of radiographic damage (odds ratio for every additional isotype: 1.4 (95% CI 1.1 to 1.9) p<0.001). ACPA isotypes supplied additional prognostic information to ACPA status alone, even after correction for other predictive factors.
  
  
  CONCLUSIONS
  The magnitude of the ACPA isotype profile at baseline reflects the risk of future radiographic damage. These results indicate that the presence and the constitution of the ACPA response are relevant to the disease course of RA.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. dvanderwoude@lumc.nl
authors.forename: Diane
authors.initials: D
authors.lastname: van der Woude
authors.forename: Silje W
authors.initials: SW
authors.lastname: Syversen
authors.forename: Ellen I H
authors.initials: EI
authors.lastname: van der Voort
authors.forename: Kirsten N
authors.initials: KN
authors.lastname: Verpoort
authors.forename: Guro L
authors.initials: GL
authors.lastname: Goll
authors.forename: Michael P M
authors.initials: MP
authors.lastname: van der Linden
authors.forename: Annette H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
authors.forename: Désirée M F M
authors.initials: DM
authors.lastname: van der Heijde
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Tore K
authors.initials: TK
authors.lastname: Kvien
authors.forename: René E M
authors.initials: RE
authors.lastname: Toes
mesh_terms: D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood*; D010456:Peptides, Cyclic / Q000276:immunology*; D011379:Prognosis; D011859:Radiography
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007132:Immunoglobulin Isotypes; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide