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HLA-DRB1*0404 is strongly associated with anticalpastatin antibodies in rheumatoid arthritis
  1. Isabelle Auger,
  2. Chantal Roudier,
  3. Sandrine Guis,
  4. Nathalie Balandraud,
  5. Jean Roudier
  1. INSERM UMR 639, Université de la Méditerranée and Rheumatology, APHM, La Conception, Marseille, France
  1. Isabelle Auger, INSERM UMR 639, Faculté de Médecine, 27 BD Jean Moulin, 13005 Marseille, France; isabelle.auger{at}


Objective: To test whether HLA-DR alleles influence the production of particular autoantibodies in rheumatoid arthritis (RA) patients, we screened synovial proteins with sera of RA patients homozygous for different HLA-DR alleles by using 2D blots. We found that sera of RA patients homozygous for HLA-DRB1*0404 recognised a 100-kDa synovial protein identified as calpastatin. We studied B and T cell epitopes on calpastatin and their association with HLA-DRB1*0404.

Methods: The frequency of positive sera in patients expressing different RA-associated HLA-DR allele combinations was calculated by inhouse ELISA using purified synovial calpastatin or calpastatin peptides encompassing the entire calpastatin protein as immunosorbent. Interaction between calpastatin peptides and HLA-DR alleles was tested by a direct binding assay. T cell responses to calpastatin were measured in RA patients and controls.

Results: We found that RA-associated HLA-DR alleles are associated with presence of autoantibodies to synovial calpastatin in RA patients’ sera. HLA-DRB1*0404 is strongly associated with antisynovial calpastatin in RA sera. One linear B cell epitope is preferentially associated with HLA-DRB1*0404. Multiple peptides from calpastatin bind every tested HLA-DR allele associated or not with RA. Peptides from domain 1 and 4 of calpastatin are the best HLA-DR allele binders. The T cell response to calpastatin is frequent in RA patients and independent of the HLA-DR background.

Conclusions: HLA-DRB1*0404 is strongly associated with anticalpastatin antibodies in rheumatoid arthritis.

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  • Competing interests: None declared.

  • Abbreviations:
    optical density
    rheumatoid arthritis
    shared epitope

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