Logo der Universität Basel

Research Database / FORSCHUNGSDATENBANK 
PRINTDOC
 
Publication 153425 | Verified
 

Data Entry: Please note that the research database will be replaced by UNIverse by the end of October 2023. Please enter your data into the system https://universe-intern.unibas.ch. Thanks

Login for users with Unibas email account...

Login for registered users without Unibas email account...

 
Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 153425
Author(s) Zanger, U M; Hauri, H P; Loeper, J; Homberg, J C; Meyer, U A
Author(s) at UniBasel Hauri, Hans-Peter
Year 1988
Title Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II
Journal Proceedings of the National Academy of Sciences of the United States of America
Volume 85
Number 21
Pages / Article-Number 8256-60
Keywords Antibodies; Monoclonal; Autoantibodies/analysis; Chromatography; Affinity; Cytochrome P-450 Enzyme System/*immunology; Electrophoresis; Polyacrylamide Gel; Endoplasmic Reticulum/immunology; Ethanolamines/pharmacology; Hepatitis; Chronic/*enzymology/immunology; Humans; Isoenzymes/*immunology; Kidney/immunology; Liver/immunology
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.
Publisher National Academy of Sciences
ISSN/ISBN 0027-8424
edoc-URL http://edoc.unibas.ch/dok/A5257828
Full Text on edoc No
Digital Object Identifier DOI 10.1073/pnas.85.21.8256
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/3186722
ISI-Number WOS:A1988Q834100091
Document type (ISI) Journal Article
 
   

MCSS v5.8 PRO. 0.325 sec, queries - 0.000 sec ©Universität Basel  |  Impressum   |    
12/05/2024