Antibody levels to mycobacteria in relation to HLA type: evidence for non-HLA-linked high levels of antibody to the 65 kD heat shock protein of M. bovis in rheumatoid arthritis.

We previously reported DR2 and DR7-associated regulation of antibody binding to mycobacteria in rheumatoid arthritis sera (RA), but not in tuberculosis (Tb). An extensive analysis of antibody to mycobacteria in matched normal sera, in relation to both HLA class I and class II has revealed no class II correlations, confirming that the original findings were due to RA. There was however a very strong association between IgM binding to M. tuberculosis and Cw1 (P = 0.0004). RA patients have strikingly raised levels of IgG (but not of IgA or IgM) binding to the 65 kD heat shock protein of M. tuberculosis, recently implicated in the pathogenesis of adjuvant arthritis in the rat. Remarkably, levels in RA were significantly higher even than in tuberculosis. Levels of this antibody showed no HLA associations. Thus the 65 kD antigen does not account for the DR7, and DR2 associations of IgM and IgA binding to mycobacteria reported previously, but does suggest a role for cross-reactive autoimmunity in RA.