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 antibodies. In autoimmune hepatitis (AIH) type 2, liver and/or kidney microsomal (LKM) type 1 autoantibodies are detected and are directed against CYP2D6. About 10% of AIH-2 sera further contain LKM-3 autoantibodies directed against family 1 UGTs. Chronic infections by hepatitis C virus and hepatitis delta virus may induce several autoimmune phenomena, and multiple autoantibodies are detected. Anti-CYP2D6 autoantibodies are detected in up to 4% of patients with chronic hepatitis C, and anti-CYP2A6 autoantibodies are detected in about 2% of these patients. In contrast, 14% of patients with chronic hepatitis delta virus infections generate anti-UGT autoantibodies. In a small minority of patients, certain drugs are known to induce immune-mediated, idiosyncratic drug reactions, also known as 'druginduced 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-CYP1A2, halothane hepatitis with anti-CYP2E1 and anticonvulsant hepatitis with anti-CYP3A. Recent data suggest that alcoholic liver disease may be induced by mechanisms similar to those that are active in drug-induced hepatitis. Autoantibodies directed against several CYPs are further detected in sera from patients with the autoimmune polyglandular syndrome type 1. Patients with autoimmune polyglandular syndrome type 1 with hepatitis often develop anti-CYP1A2; patients with adrenal failure develop anti-CYP21, anti- CYP11A1 or CYP17; and patients with gonadal failure develop anti-CYP11A1 or CYP17. In idiopathic Addison disease, CYP21 is the major autoantigen.
Obermayer-Straub
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Medizinische Hochschule Hannover, Hannover, Germany.
Strassburg
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Manns
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D001323:Autoantibodies / Q000502:physiology*; D015551:Autoimmunity; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology; D019389:Cytochrome P-450 CYP2D6 / Q000276:immunology; D019392:Cytochrome P-450 CYP2E1 / Q000276:immunology; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology*; D004078:Dihydralazine / Q000009:adverse effects; D014453:Glucuronosyltransferase / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000276:immunology; D006801:Humans; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology
D001323:Autoantibodies; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D019389:Cytochrome P-450 CYP2D6; D014453:Glucuronosyltransferase; D004078:Dihydralazine