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Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II

Zanger, U. M. and Hauri, H. P. and Loeper, J. and Homberg, J. C. and Meyer, U. A.. (1988) Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II. Proceedings of the National Academy of Sciences of the United States of America, Vol. 85, H. 21. S. 8256-8260.

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Official URL: http://edoc.unibas.ch/dok/A5257828

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Abstract

In a subgroup of children with chronic active hepatitis, circulating autoantibodies occur that bind to liver and kidney endoplasmic reticulum (anti-liver/kidney microsome antibody type I or anti-LKM1). Anti-LKM1 titers follow the severity of the disease and the presence of these antibodies serves as a diagnostic marker for this autoimmune hepatitis type II. We demonstrate that anti-LKM1 IgGs specifically inhibit the hydroxylation of bufuralol in human liver microsomes. Using two assay systems with different selectivity for the two cytochrome P-450 isozymes catalyzing bufuralol metabolism in human liver, we show that anti-LKM1 exclusively recognizes cytochrome P-450db1. Immunopurification of the LKM1 antigen from solubilized human liver microsomes resulted in an electrophoretically homogenous protein that had the same molecular mass (50 kDa) as purified P-450db1 and an identical N-terminal amino acid sequence. Recognition of both purified P-450db1 and the immunoisolated protein on western blots by several monoclonal antibodies confirmed the identity of the LKM1 antigen with cytochrome P-450db1. Cytochrome P-450db1 has been identified as the target of a common genetic polymorphism of drug oxidation. However, the relationship between the polymorphic cytochrome P-450db1 and the appearance of anti-LKM1 autoantibodies as well as their role in the pathogenesis of chronic active hepatitis remains speculative.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Pharmacology/Neurobiology (Hauri)
UniBasel Contributors:Hauri, Hans-Peter
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:National Academy of Sciences
ISSN:0027-8424
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:20
Deposited On:22 Mar 2012 13:19

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