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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 P M van der Linden1,
  8. Benedicte Lie2,
  9. Tom W J Huizinga1,
  10. Désirée M F M van der Heijde1,2,
  11. Annette H M van der Helm-van Mil1,
  12. Tore K Kvien2,
  13. René E M Toes1
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands
  2. 2Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway

Abstract

Objectives HLA shared epitope (SE) alleles are associated with joint destruction, the presence of anticitrullinated protein antibodies (ACPA) and are known to shape the ACPA fine-specificity repertoire in rheumatoid arthritis (RA). A large variation in the extent of joint destruction is seen within the ACPA-positive patient population, and it is conceivable that certain ACPA reactivities contribute most to radiological damage. Here, we 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 by ELISA 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 long-term 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 the extent of radiographic joint damage. Most relevant, 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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