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Distinct ACPA fine specificities, formed under the influence of HLA shared epitope alleles, have no effect on radiographic joint damage in rheumatoid arthritis
  1. Hans Ulrich Scherer1,
  2. Diane van der Woude1,
  3. Annemiek Willemze1,
  4. Leendert A Trouw1,
  5. Rachel Knevel1,
  6. Silje W Syversen2,
  7. Michael PM van der Linden1,
  8. Benedicte Lie2,
  9. Tom WJ Huizinga1,
  10. Désirée MFM van der Heijde1,2,
  11. Annette HM van der Helm-van Mil1,
  12. Tore K Kvien2,
  13. René EM Toes1
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  1. Correspondence to René EM Toes, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands; r.e.m.toes{at}


Objectives Human leucocyte antigen shared epitope (SE) alleles are associated with joint destruction, the presence of anticitrullinated protein antibodies (ACPA) and the ACPA fine specificity repertoire in rheumatoid arthritis (RA). A large variation in joint destruction is seen within the ACPA-positive patient population, and it is conceivable that certain ACPA reactivities contribute to radiological damage. The authors investigated whether ACPA fine specificities, which are formed under the influence of SE alleles, associate with the extent of radiographic joint damage.

Methods Antibodies recognising six citrullinated epitopes were determined in sera of 330 ACPA-positive RA patients genotyped for SE alleles. The association between SE alleles, ACPA fine specificity and radiographic joint damage was assessed using radiographic follow-up data. A second cohort of 154 RA patients with 5 and 10-year radiographic follow-up was used for replication.

Results SE alleles predisposed to the recognition of certain citrullinated epitopes. However, none of the ACPA fine specificities studied influenced radiographic joint damage. Importantly, although SE alleles associated with radiographic damage in the total RA population, this association was no longer detectable after stratification for the presence of ACPA.

Conclusions SE alleles are instrumental in shaping the ACPA repertoire. However, ACPA fine specificities formed under the influence of SE alleles do not seem to affect joint destruction.

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  • Funding This study was supported by grants from the Kassenaarfonds, the Centre for Medical Systems Biology and the National Proteomics Center within the framework of The Netherlands Genomics Initiative (NGI); the European Union (Sixth Framework Program integrated project Autocure and Seventh Framework Program integrated project Masterswitch); NWO ZonMW AGIKO, VENI and VICI grants from The Netherlands Organization for Scientific Research and from The Netherlands Organization of Health Research.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Leiden University Medical Center.

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

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