Article Text

Download PDFPDF
Extended report
The ACPA recognition profile and subgrouping of ACPA-positive RA patients
  1. Annemiek Willemze1,
  2. Stefan Böhringer2,
  3. Rachel Knevel1,
  4. EW Nivine Levarht1,
  5. Gerrie Stoeken-Rijsbergen1,
  6. Jeanine J Houwing-Duistermaat2,
  7. Annette HM van der Helm-van Mil1,
  8. Tom WJ Huizinga1,
  9. René EM Toes1,
  10. Leendert A Trouw1
  1. 1Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
  2. 2Department of Medical Statistics and Bioinformatics, Leiden University Medical Center (LUMC), Leiden, The Netherlands
  1. Correspondence to Annemiek Willemze, Department of Rheumatology, Leiden University Medical Center, P.O.Box 9600, 2300 RC Leiden, The Netherlands; a.willemze{at}


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.

Conclusion 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.

View Full Text

Statistics from


  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval METC LUMC.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.