IDENTIFICATION OF THE MAIN GONADAL AUTOANTIGENS IN PATIENTS WITH ADRENAL INSUFFICIENCY AND ASSOCIATED OVARIAN FAILURE

Autoimmune adrenal insufficiency is associated with premature ovarian failure at frequencies of 10-20%. In these patients a reactivity again st an unknown steroid cell antigen in both the adrenal glands and gona ds has been described. We have recently identified the cytochrome P450 enzyme 21-hydroxylase and the side-chain cleavage enzyme (SCC) as the major adrenal autoantigens in Addison's disease and the rare autoimmu ne polyendocrine syndrome type I (APS-I), respectively. In an attempt to identify the steroid cell antigen, sera from patients with Addison' s disease (n = 13) and APS-I (n = 7) that reacted with Leydig cells we re selected. Preparations of isolated human granulosa cells, isolated rat Leydig cells, and fractions of human placenta were used in Western blots. All sera were also tested against bacterially expressed 21-hyd roxylase, SCC, and 17 alpha-hydroxylase. The SCC was recognized by ser a from patients with Addison's disease and those with APS-I. In additi on, a majority of the sera (n = 12) reacted with a novel 51-kilodalton autoantigen present in granulosa cells and placenta. The results show that the steroid cell autoantigen consists mainly of the SCC and a no vel protein of unknown function.