Conroy, Susan Esther; (1995) Antibodies to heat shock proteins in patients with systemic lupus erythematosus and in patients with breast cancer. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Elevated levels of heat shock protein 90 (hsp90) have been detected in the peripheral blood mononuclear cells (PBMCs) of approximately 25% of patients with systemic lupus erythematosus (SLE) compared to healthy controls. In contrast there is no increase in the expression of the constitutive hsp73, hsp60 or in the rate of transcription of the ubiquitin gene in SLE patients. Hence, among lupus patients, elevation of hsp90 is restricted to a subset of patients and is not a general response to cellular stress. Although not normally expressed on the cell surface, hsp90 has been found on the surface of PBMCs in approximately 20% of patients with SLE. Thus the increased levels of hsp90 in some of the SLE patients may result in a proportion of the protein, or some component of it, becoming localised to the cell surface. The hsp90 on the cell surface could thus become the target of the immune system leading to the production of autoantibodies to hsp90. To investigate this hypothesis a suitable method for detecting these antibodies in sera was devised. Previous methodology used a complex Western blot system and resulted in conflicting data. An ELISA was established to detect antibodies to native hsp90 in the sera from patients with SLE, other autoimmune diseases and healthy controls. IgM and IgG anti- hsp90 antibodies were found in 35% and 26% of SLE patients respectively. An ELISA was established to investigate whether these antibodies were part of a generalised anti-hsp response or specific to hsp90. In contrast less than 10% of patients had elevated levels of antibodies of either isotype to hsp70. This observation was extended to investigate antibodies to hsps to children with SLE, chronic arthritis, dermatomyositis and non-autoimmune controls. Increased hsp expression has been observed in patients with malignant cancers with variable prognostic associations. Elevated hsp90 has been shown to correlate with poor prognosis in patients with breast cancer. Sera from 126 patients with breast cancer were tested for antibodies to hsp90 using the ELISA described above. Elevated levels of anti-hsp90 antibodies were detected in 38% of patients with malignant but not benign breast cancer and correlations with clinical parameters were investigated.

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