Target Proteins in Human Autoimmunity: Cytochromes P450 and Udp-GlycoronosyltransferasesReport as inadecuate




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Canadian Journal of Gastroenterology - Volume 14 2000, Issue 5, Pages 429-439

Mini-Review Department of Gastroenterology and Hepatology, Hannover Medical School, Germany

Received 7 December 1998; Revised 11 December 1998

Copyright © 2000 Hindawi Publishing Corporation. This open-access article is distributed under the terms of the Creative Commons Attribution Non-Commercial License CC BY-NC http:-creativecommons.org-licenses-by-nc-4.0-, which permits reuse, distribution and reproduction of the article, provided that the original work is properly cited and the reuse is restricted to noncommercial purposes.

Abstract

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 ’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-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.





Author: Petra Obermayer-Straub, Christian Peer Strassburg, and Michael Peter Manns

Source: https://www.hindawi.com/



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