title: Distinct ACPA fine specificities, formed under the influence of HLA shared epitope alleles, have no effect on radiographic joint damage in rheumatoid arthritis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hans Ulrich
authors.initials: HU
authors.lastname: Scherer
authors.forename: Diane
authors.initials: D
authors.lastname: van der Woude
authors.forename: Annemiek
authors.initials: A
authors.lastname: Willemze
authors.forename: Leendert A
authors.initials: LA
authors.lastname: Trouw
authors.forename: Rachel
authors.initials: R
authors.lastname: Knevel
authors.forename: Silje W
authors.initials: SW
authors.lastname: Syversen
authors.forename: Michael P M
authors.initials: MP
authors.lastname: van der Linden
authors.forename: Benedicte
authors.initials: B
authors.lastname: Lie
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Désirée M F M
authors.initials: DM
authors.lastname: van der Heijde
authors.forename: Annette H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
authors.forename: Tore K
authors.initials: TK
authors.lastname: Kvien
authors.forename: René E M
authors.initials: RE
authors.lastname: Toes
mesh_terms: D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D018450:Disease Progression; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D010456:Peptides, Cyclic / Q000276:immunology*; D011379:Prognosis; D011859:Radiography
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide