Heat shock proteins as potential targets in the therapy of inflammatory arthritis.
Whether heat shock proteins (hsp) will be therapeutic targets in arthritis depends on their role in pathogenesis. In this article, three possibilities are considered. Firstly, an excessive immune response to bacterial hsp could be arthritogenic - as may occur in reactive arthritis. In these circumstances therapy would be directed to down-regulating this immune response, or altering the nature of the immune response e.g. by changing cytokine production from interferon-g to IL-4. However this approach depends on the immune response to bacterial hsp not being critical for control of the bacterial infection. Secondly, an immune response to bacterial hsp may induce autoimmunity by cross-reactivity, e.g. with the homologous human. This could also be modulated in the same way with a lower likelihood of interfering with control of the infectious agent, since only a component of the immune response against the bacterial hsp will be cross-reactive with self. Thirdly, recent experiments raise the possibility that joint inflammation might be controlled by T cells which recognizes self hsp, particularly hsp60. Therapies might enhance this response; protection from experimental arthritis by prior immunization with hsp60 is well established. Whether similar approaches will be viable after arthritis is established remains to be seen.
Gaston
J S
JS
University of Cambridge, School of Clinical Medicine, Dept. of Medicine, UK.
D000818:Animals; D000942:Antigens, Bacterial; D001168:Arthritis / Q000209:etiology / Q000276:immunology* / Q000628:therapy*; D016918:Arthritis, Reactive / Q000209:etiology / Q000276:immunology / Q000628:therapy; D001324:Autoantigens; D015551:Autoimmunity; D001426:Bacterial Proteins / Q000276:immunology; D003429:Cross Reactions; D004195:Disease Models, Animal; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial; D001324:Autoantigens; D001426:Bacterial Proteins; D006360:Heat-Shock Proteins