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HLA-DRB1*0404 is strongly associated with anti- calpastatin antibodies in rheumatoid arthritis
  1. Isabelle Auger (isabelle.auger{at}medecine.univ-mrs.fr)
  1. INSERM UMR 639, France
    1. Chantal Roudier (chantal.roudier{at}medecine.univ-mrs.fr)
    1. INSERM UMR 639, France
      1. Sandrine Guis (sandrine.guis{at}medecine.univ-mrs.fr)
      1. INSERM UMR 639, France
        1. Nathalie Balandraud (nathalie.balandraud{at}medecine.univ-mrs.fr)
        1. INSERM UMR 639, France
          1. Jean Roudier (jean.roudier{at}medecine.univ-mrs.fr)
          1. INSERM UMR 639, France

            Abstract

            Objective: To test whether HLA-DR alleles influence the production of particular autoantibodies in 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 recognized a 100 kD 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 in-house 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 anti synovial 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 alleles binders. 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 anti calpastatin antibodies in rheumatoid arthritis.

            • Autoantibodies
            • Calpastatin
            • HLA-DRB1*0404
            • Rheumatoid arthritis

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