The Involvement of Heat-Shock Proteins in the Pathogenesis of Autoimmune Arthritis: A Critical Appraisal

Objectives: To review the literature on the role of heat-shock proteins (HSPs) in the pathogenesis of autoimmune arthritis in animal models and patients with rheumatoid arthritis (RA). Methods: The published literature in Medline (PubMed), including our published work on the cell-mediated as well as humoral immune response to various HSPs, was reviewed. Studies in the preclinical animal models of arthritis as well as RA were examined critically and the data are presented. Results: In experimental arthritis, disease induction by different arthritogenic stimuli, including an adjuvant, led to immune response to mycobacterial HSP65 (BHSP65). However, attempts to induce arthritis by a purified HSP have not met with success. There are several reports of a significant immune response to HSP65 in RA patients. However, the issue of cause and effect is difficult to address. Nevertheless, several studies in animal models and a couple of clinical trials in RA patients have shown the beneficial effect of HSPs against autoimmune arthritis. Conclusions: There is a clear association between immune response to HSPs, particularly HSP65, and the initiation and propagation of autoimmune arthritis in experimental models. The correlation is relatively less convincing in RA patients. In both cases, the ability of HSPs to modulate arthritis offers support, albeit an indirect one, for the involvement of these antigens in the disease process. (C) 2010 Published by Elsevier Inc. Semin Arthritis Rheum 40:164-175