Faulds, Gary Bryan; (1995) Hsp 90 in lupus-prone mice. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The role of heat shock proteins in the development of autoimmune disease remains under close scrutiny. In humans Hsp90 is overexpressed in the peripheral blood mononuclear cells (PBMCs) of approximately 30[percent] of systemic lupus erythematosus (SLE) patients, and overexpression of this protein is associated with some types of active disease. This study was set up to investigate the role of hsps in the murine lupus-prone strain MRL/lpr. Comparable overexpression of the 90kD heat shock protein was detected in the spleens of these mice, and levels of this protein were significantly elevated compared with healthy controls (p[less-than] 0.005). In MRL/Ipr mice elevation of Hsp90 is associated with active disease and elevated levels of Hsp90 are detected around the time of disease onset. No other tissue appeared to overexpress Hsp90, although a general rise in the levels of Hsp72, the inducible member of the 70kD heat shock protein family, was noted in a number of tissues. Neither the constitutively expressed Hsp73 protein nor the Hsp60 chaperonin were overexpressed in MRL/ipr mice compared with healthy Balb/c controls. The immune response to Hsp90 was examined, and antibodies were found which recognised Hsp90, Hsp70 and Hsp60 in the autoimmune mice, at greater concentrations than antibodies detected in control animals. Levels of anti-Hsp90 antibodies rose with increasing age and appeared around the time of disease onset. Anti-Hsp90 antibodies were detected in approximately 60[percent] of MRL/lpr mice over the age of 12 weeks. Levels of antibodies to Hsp90 were not correlated with other serological manifestations of the disease, however, whereas antibodies to Hsp70 and Hsp60 also rose with age and were significantly correlated in MRL/lpr mice (p=0.002), and in the congenic strain MRL/++ (p=0.001). Levels of these antibodies and levels of anti-Hsp90 antibodies in MRL/lpr mice were not correlated. These findings parallel results from studies undertaken on patients with SLE.

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