2 CYTOCHROMES P450 ARE MAJOR HEPATOCELLULAR AUTOANTIGENS IN AUTOIMMUNE POLYGLANDULAR SYNDROME TYPE-1

Background & Aims: Liver disease has been described in 10%-15% of pati ents with autoimmune polyglandular syndrome type 1 (APS-1), After the discovery of cytochrome P450 1A2 (CYP1A2) as a hepatocellular autoanti gen in liver-kidney microsomal autoantibody (LKM)-positive patients wi th APS-1, the investigation of antiliver antibodies was extended to 11 Sardinian patients with APS-1, Methods: Indirect immunofluorescence a nd Western blotting analysis were performed to study the antiliver ant ibodies, Results: Immunofluorescence revealed LKM antibodies in 3 pati ents with APS-1, 1 of whom died of fulminant hepatitis, Western blotti ng showed a liver microsomal protein band of approximately 51 kilodalt ons in the LKM-positive sera of these 3 patients, Western blotting per formed with recombinant cytochrome P450 enzymes allowed the identifica tion of CYP2A6 as a specific target antigen, Conclusions: LKM antibodi es in APS-1 sera are specifically directed against CYP1A2 or CYP2A6, b ut their diagnostic and prognostic significance for liver disease rema in to be determined.