Target Proteins in Human Autoimmunity: Cytochromes P450 and Udp-Glycoronosyltransferases
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...
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| Format: | Article |
| Language: | English |
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Wiley
2000-01-01
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| Series: | Canadian Journal of Gastroenterology |
| Online Access: | http://dx.doi.org/10.1155/2000/910107 |
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| author | Petra Obermayer-Straub Christian Peer Strassburg Michael Peter Manns |
| author_facet | Petra Obermayer-Straub Christian Peer Strassburg Michael Peter Manns |
| author_sort | Petra Obermayer-Straub |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-89b725110ba8431893141ab4f0e94470 |
| institution | Kabale University |
| issn | 0835-7900 |
| language | English |
| publishDate | 2000-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Canadian Journal of Gastroenterology |
| spelling | doaj-art-89b725110ba8431893141ab4f0e944702025-02-03T05:59:08ZengWileyCanadian Journal of Gastroenterology0835-79002000-01-0114542943910.1155/2000/910107Target Proteins in Human Autoimmunity: Cytochromes P450 and Udp-GlycoronosyltransferasesPetra Obermayer-Straub0Christian Peer Strassburg1Michael Peter Manns2Department of Gastroenterology and Hepatology, Hannover Medical School, GermanyDepartment of Gastroenterology and Hepatology, Hannover Medical School, GermanyDepartment of Gastroenterology and Hepatology, Hannover Medical School, GermanyCytochromes 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.http://dx.doi.org/10.1155/2000/910107 |
| spellingShingle | Petra Obermayer-Straub Christian Peer Strassburg Michael Peter Manns Target Proteins in Human Autoimmunity: Cytochromes P450 and Udp-Glycoronosyltransferases Canadian Journal of Gastroenterology |
| title | Target Proteins in Human Autoimmunity: Cytochromes P450 and Udp-Glycoronosyltransferases |
| title_full | Target Proteins in Human Autoimmunity: Cytochromes P450 and Udp-Glycoronosyltransferases |
| title_fullStr | Target Proteins in Human Autoimmunity: Cytochromes P450 and Udp-Glycoronosyltransferases |
| title_full_unstemmed | Target Proteins in Human Autoimmunity: Cytochromes P450 and Udp-Glycoronosyltransferases |
| title_short | Target Proteins in Human Autoimmunity: Cytochromes P450 and Udp-Glycoronosyltransferases |
| title_sort | target proteins in human autoimmunity cytochromes p450 and udp glycoronosyltransferases |
| url | http://dx.doi.org/10.1155/2000/910107 |
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