2 DIFFERENT CYTOCHROME-P450 ENZYMES ARE THE ADRENAL ANTIGENS IN AUTOIMMUNE POLYENDOCRINE SYNDROME TYPE-I AND ADDISONS-DISEASE

Autoimmune polyendocrine syndrome type I (APS I) and idiopathic Addiso n's disease are both disorders with adrenal insufficiency but with dif ferences in genetic background, clinical presentation, and extent of e xtraadrenal manifestations. In this study the major adrenal autoantige n identified with sera from patients with APS I was characterized by a nalyses using indirect immunofluorescence, Western blots of adrenal su bcellular fractions and of recombinant proteins, immunoprecipitations of [S-35]methionine-labeled lysates of a human steroid-producing cell line, and studies of enzymatic activity. Sera from patients with APS I , identifying cells in adrenal glands and testes involved in steroid s ynthesis, reacted in Western blots with a 53-kD antigen, which comigra ted with the cytochrome P450 cholesterol side chain cleavage enzyme (S CC). The sera also immunoprecipitated this protein from lysates of rad iolabeled adrenal cells. The enzymatic activity of SCC was inhibited b y the APS I sera but not by control sera. Sera from patients with idio pathic Addison's disease did not react with the SCC. The results show that the autoimmune responses towards adrenal tissue in patients suffe ring from APS I and Addison's disease are remarkably selective and sug gest that a determination of the antigen involved in a patient with au toimmune adrenal insufficiency will have diagnostic as well as prognos tic implications.