Rheumatoid Arthritis Research Today is a free monthly online journal that collates and summarizes the latest research about Rheumatoid Arthritis, including details on treatment, symptoms, causes, medication.

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

Auger I, Roudier C, Guis S, Balandraud N, Roudier J

INSERM UMR 639, Faculté de Médecine, 27 BD Jean Moulin, 13005 Marseille, France. isabelle.auger@medecine.univ-mrs.fr

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.

Published 13 November 2007 in Ann Rheum Dis, 66(12): 1588-93.
Full-text of this article is available online (may require subscription).

© 2004-2008 Rheumatoid Arthritis Research Today. All Rights Reserved.