title: The ACPA recognition profile and subgrouping of ACPA-positive RA patients.
abstract: OBJECTIVE
  Anticitrullinated protein antibodies (ACPA) are the most predictive factor for the development of rheumatoid arthritis (RA). Epitope spreading towards more citrullinated epitopes occurs before the onset of RA. Here, the authors investigated whether specific epitope recognition allows the identification of specific RA subgroups and whether it is associated with clinical features of RA.
  
  
  METHODS
  The reactivity of 661 patients with RA from the Leiden Early Arthritis Clinic against several citrullinated antigens was determined by ELISA. Cluster analyses were performed to identify subgroups of patients on the basis of their ACPA recognition profile. The association of the specific reactivities with clinical characteristics was studied.
  
  
  RESULTS
  ACPA-positive patients displayed a heterogeneous ACPA recognition profile. After performing cluster analyses, no apparent clustering of patients was found, and on the basis of the reactivities analysed, 64 different subgroups could already be identified. The extent of epitope recognition was associated with anticyclic citrullinated peptide-2 levels. The recognition of specific citrullinated epitopes was not associated with baseline characteristics. Likewise, patients with an extended fine specificity repertoire did not display differences in baseline characteristics or joint damage after 7 years of follow-up using cyclic citrullinated peptide-2 levels as a proxy, compared to ACPA-positive patients recognising fewer peptides.
  
  
  CONCLUSIONS
  These data show that the ACPA response is highly diverse with respect to recognition of specific citrullinated epitopes. Furthermore, the authors' data indicate that clinical correlates in established ACPA-positive RA are independent from the specific (group of) citrullinated peptides recognised.
authors: Department of Rheumatology, Leiden University Medical Center, The Netherlands. a.willemze@lumc.nl
authors: Annemiek
authors: A
authors: Willemze
authors: Stefan
authors: S
authors: Böhringer
authors: Rachel
authors: R
authors: Knevel
authors: E W Nivine
authors: EW
authors: Levarht
authors: Gerrie
authors: G
authors: Stoeken-Rijsbergen
authors: Jeanine J
authors: JJ
authors: Houwing-Duistermaat
authors: Annette H M
authors: AH
authors: van der Helm-van Mil
authors: Tom W J
authors: TW
authors: Huizinga
authors: René E M
authors: RE
authors: Toes
authors: Leendert A
authors: LA
authors: Trouw
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000145:classification / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016000:Cluster Analysis; D018450:Disease Progression; D000939:Epitopes / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D000939:Epitopes; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002097:C-Reactive Protein