AUTOANTIBODIES TO CYTOCHROME-P450 ENZYMES P450SCC, P450C17, AND P450C21 IN AUTOIMMUNE POLYGLANDULAR DISEASE TYPE-I AND TYPE-II AND IN ISOLATED ADDISONS-DISEASE

Patients with idiopathic Addison's disease have autoantibodies reactin g with adrenal cortex. If Addison's disease is associated with other e ndocrine immune diseases like autoimmune polyglandular diseases (APD) type I and type II, antibodies may recognize all steroid-producing cel ls. We showed previously that one antigen recognized by APD-I sera is the cytochrome P450c17 hydroxylase. We have now looked for antibodies to P450c17 and to two other key enzymes in the steroid biosynthetic pa thway, the P450scc and P450c21, in a series of patients with isolated Addison's disease (8 patients) or with APD-I or APD-II (50 and 9 patie nts, respectively). The result of antienzyme antibodies were further c orrelated with the immunofluorescence pattern against adrenal gland, t estis, ovary, and placenta, and with the clinical findings presented. In APD-I patients with Addison's disease and in APD-II patients, antib odies to at least one of the P450 enzymes were frequently found (posit ive findings in 81% and 78%, respectively). Such antibodies were less frequent in APD-I patients without Addison's disease (21%) and in the isolated Addison cases (25%). In APD-I, antibodies recognized as frequ ently P450c17 and P450scc, specific for all steroid-producing cells as the adrenal specific enzyme P450c21. In contrast, patients with APD-I I or with the isolated Addison's disease reacted almost exclusively wi th P450c21. Immunofluorescence studies showed good correlation with th e known fact that the tons glomerulosa of the adrenal cortex is devoid of the P450c17, that the Leydig cells of the testis and the theca int erna cells of the ovary express P450c17 and P450scc, and that the plac ental trophoblasts express only P450scc. The presence of antibodies to P450scc or to at least one of the tested P450 enzymes correlated sign ificantly to gonadal failure in the females but not in the males.