{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:47:53Z","timestamp":1792741673700,"version":"4.5.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1988,11]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1073\/pnas.85.21.8256","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T06:45:04Z","timestamp":1149057904000},"page":"8256-8260","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":165,"title":["Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II."],"prefix":"10.1073","volume":"85","author":[{"given":"U M","family":"Zanger","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H P","family":"Hauri","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Loeper","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J C","family":"Homberg","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U A","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Basel, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1988,11]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.85.21.8256","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T12:40:04Z","timestamp":1649853604000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.85.21.8256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1988,11]]},"references-count":0,"journal-issue":{"issue":"21","published-print":{"date-parts":[[1988,11]]}},"alternative-id":["10.1073\/pnas.85.21.8256"],"URL":"https:\/\/doi.org\/10.1073\/pnas.85.21.8256","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1988,11]]},"assertion":[{"value":"1988-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}