Target proteins in human autoimmunity: Cytochromes p450 and UDP-glucuronosyltransferases

Cytochromes P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) are targets of autoantibodies in several hepatic and extrahepatic autoimmune diseases. Autoantibodies directed against hepatic CYPs and UGTs were first detected by indirect immunofluorescence as antiliver and/or kidney microsomal antibo dies. In autoimmune hepatitis (AIH) type 2, liver and/or kidney microsomal (LKM) type 1 autoantibodies are detected and are directed against CYP2D6. A bout 10% of AIH-2 sera further contain LKM-3 autoantibodies directed agains t family 1 UGTs. Chronic infections by hepatitis C virus and hepatitis delt a virus may induce several autoimmune phenomena, and multiple autoantibodie s are detected. Anti-CYP2D6 autoantibodies are detected in up to 4% of pati ents with chronic hepatitis C, and anti-CYP2A6 autoantibodies are detected in about 2% of these patients. In contrast, 14% of patients with chronic he patitis delta virus infections generate anti-UGT autoantibodies. In a small mi nority of patients, certain drugs are known to induce immune mediated, idiosyncratic drug reactions, also known as 'drug-induced hepatitis'. Drug- induced hepatitis is often associated with autoantibodies directed against hepatic CYPs or other hepatic proteins. Typical examples are tienilic acid induced hepatitis with anti-CYP2C9, dihydralazine hepatitis with anti CYP1A 2, halothane hepatitis with anti-CYP2E1 and anticonvulsant hepatitis with a nti-CYP3A. Recent data suggest that alcoholic liver disease may be induced by mechanisms similar to those that are active in drug-induced hepatitis. A utoantibodies directed against several CYPs are further detected in sera fr om patients with the autoimmune polyglandular syndrome type 1. Patients wit h autoimmune polyglandular syndrome type 1 with hepatitis often develop ant i- CYP1A2; patients with adrenal failure develop anti-CYP21, anti-CYP11A1 o r CYP17; and patients with gonadal failure develop anti-CYP11A1 or CYP17. T n idiopathic Addison disease, CYP21 is the major autoantigen.