The Unmysterious Roles of HSP90: Ovarian Pathology and Autoantibodies

The heat shock proteins (HSPs) are a group of evolutionarily conserved proteins with important physiological functions, whose synthesis is enhanced by elevated temperature or other stresses. HSPs show high sequence homology between different species, from bacteria to humans. Despite the significant degree of evolutionary conservation, HSPs are highly immunogenic. Of the several HSPs, HSP90 is an abundant, constitutively expressed chaperone constituting around 1-2% of total cellular protein under non-stress conditions. This protein from even the most distantly related eukaryotes has 50% amino acid identity, and all have more than 40% identity with the Escherichia coli protein. They are immunodominant antigens for many common microbes, and thus their epitopes are recognized by the immune system. As HSPs are overexpressed at sites of acute and chronic inflammation, individuals are likely to be sensitized during the course of a microbial infection encountered during life. This chapter considers the evidence of a role for HSP90 in autoimmune ovarian failure, where autoantibodies to it have been observed in patients, and has been correlated to infertility.