CYTOCHROME P450IA2 AND AROMATIC L-AMINO-ACID DECARBOXYLASE ARE HEPATIC AUTOANTIGENS IN AUTOIMMUNE POLYENDOCRINE SYNDROME TYPE-I

Autoimmune chronic active hepatitis (AI-CAH) is a feared component of autoimmune polyendocrine syndrome type I (APS I), In this study, immun oreactivity was assessed in sera from eight APS I patients, of whom th ree had;U-CAH, in an attempt to identify hepatic autoantigens. We perf ormed indirect immunofluorescence staining of human and rat liver sect ions, Western blots on subcellular fractions of human and rat liver, i mmunoprecipitations of labelled aromatic L-amino acid decarboxylase (A ADC) and cytochrome P450IA2 (CYP IA2) expressed by an in vitro transcr iption and translation system and studies of enzymatic activity, Autoa ntibodies against AADC were present in sera from all eight APS I patie nts, while immunoreactivity against CYP LA2 was only found in sera fro m the three APS I patients with AI-CAH. Enzymatic activity of CYP LA2 was inhibited by sera from APS I patients with AI-CAH but not by contr ol sera, Our results show that CYP IA2 and AADC constitute hepatic aut oantigens in patients with APS I and that immunoreactivity against CYP IA2 is associated with the presence of AI-CAH. (C) 1997 Federation of European Biochemical Societies.