The regulation of heat shock proteins and their role in systemic lupus erythematosus.

OBJECTIVES

After a serendipitous suggestion, it was established that a significant subset of patients with systemic lupus erythematosus (SLE) overexpress the 90-kD heat shock protein (Hsp90). In this review, we have analyzed our own data and that of others, to explore the link between Hsp90 and SLE.

METHODS

We performed a detailed literature review focusing on the potential role of Hsp in the etiopathogenesis of SLE.

RESULTS

Data are discussed showing surface expression of this Hsp in patients with lupus, a similar overexpression in the splenocytes of MRL/Ipr mice before the onset of disease, the detection of antibodies to Hsp90 in a proportion of both lupus patients and lupus-prone mice, and most recently, an analysis of the transcription factors that regulate the production of this protein and the influence of key cytokines on these factors.

CONCLUSIONS

These observations provide a model to show how a protein with key physiological roles in healthy individuals may, on occasion, become the target of an autoimmune attack with clinical consequences recognized in both mouse and human. Given that up to now, other heat shock proteins are not targeted in a similar fashion, the specificity of these responses is remarkable.