Two different cytochromes P450 are major hepatocellular autoantigen in Autoimmune Polyglandular Syndrome Type 1

BACKGROUND & AIMS: Liver disease has been described in 10%-15% of patients with autoimmune polyglandular syndrome type 1 (APS-1). After the discovery of cytochrome P450 1A2 (CYP1A2) as a hepatocellular autoantigen in liver-kidney microsomal autoantibody (LKM)-positive patients with APS-1, the investigation of antiliver antibodies was extended to 11 Sardinian patients with APS-1. METHODS: Indirect immunofluorescence and Western blotting analysis were performed to study the antiliver antibodies. RESULTS: Immunofluorescence revealed LKM antibodies in 3 patients with APS-1, 1 of whom died of fulminant hepatitis. Western blotting showed a liver microsomal protein band of approximately 51 kilodaltons in the LKM-positive sera of these 3 patients. Western blotting performed with recombinant cytochrome P450 enzymes allowed the identification of CYP2A6 as a specific target antigen. CONCLUSIONS: LKM antibodies in APS-1 sera are specifically directed against CYP1A2 or CYP2A6, but their diagnostic and prognostic significance for liver disease remain to be determined.