Autoimmunity to endoplasmic reticulum chaperone GRP94 in myasthenia gravis

Abstract

Immune responses to ER stress have been closely related to the pathogenesis of autoimmune diseases. Using an immunoprecipitation assay, 24 (7.1%) of 336 MG serum samples immunoprecipitated a 90-kDa protein from the muscle cellular extracts, but none of the disease or healthy control sera. The 90-kDa protein was affinity-purified and found to match to ER chaperon GRP94 by matrix-assisted laser desorption/ionization-time of flight mass spectroscopy analysis. The frequency of associated autoimmune diseases was much higher in the anti-GRP94-positive than the -negative patients (71% versus 11%, p < 0.001). Autoimmunity to ER chaperone GRP94 is associated with a subset of MG patients who have additional autoimmune diseases.