Immunity to heat shock proteins in rheumatoid arthritis

Heat shock proteins (hsp) or "stress proteins" are a group of highly conserved proteins which are important in the day to day function of all cells. Early studies by others have indicated that immunity to the 65 kDa hsp of mycobacteria is important in the development of arthritis in the adjuvant arthritis model in rats. In this paper, we review the evidence suggesting that, as for the rat model, immune reactivity to hsp is of importance in the human disease. Elevated levels of IgG antibodies to the 65 kDa hsp of mycobacteria are characteristic of rheumatoid arthritis (RA) patients. Much of this antibody cross-reacts with human 65 kDa hsp and is therefore autoreactive. The 65 kDa hsp is found in synovial fluid and is therefore a potential target for antibody. Antibodies to the 70 kDa hsp (both of mycobacterial and human origin) are elevated, but not specifically, in RA. Increased T cell responses to the 65 kDa hsp are also found in synovial fluid of RA patients. Although gamma delta T cells are present in the synovial joint of RA patients, they do not appear to be particularly increased in frequency although the subset distribution of these cells is clearly different from that seen in the circulation. In fact, the synovium looks like the "gut" with regard to these subsets!