{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:28:47Z","timestamp":1781101727337,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"22","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>Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the presence of antimitochondrial antibodies in the serum. It is possible that the PBC-specific immunoreactive trypsin-sensitive antigens on the inner mitochondrial membrane, termed M2, are important in the pathogenesis of this autoimmune disease. We have previously shown that a major M2\"a\" antigen is the E2 component of the pyruvate dehydrogenase multienzyme complex located within mitochondria. Analysis of the primary structure of the E2 components of all three 2-oxo acid dehydrogenase complexes reveals a high degree of homology with a similar highly segmented structure including lipoyl domains, E3-binding domains, C-terminal catalytic domains, and interdomain linker sequences. Immunoblotting of PBC patients' sera against purified E2 protein from 2-oxoglutarate dehydrogenase complex and branched-chain 2-oxo acid dehydrogenase complex reveals that these polypeptides are also autoantigens in this disease. Sera from 29 of 40 (72.5%) PBC patients gave a positive response against bovine 2-oxoglutarate dehydrogenase complex E2 and from 25 of 40 (62.5%) PBC patients gave a positive response against bovine branched-chain 2-oxo acid dehydrogenase complex E2. All 40 PBC patients (100%) have autoantibodies directed against at least one of the E2 components of the family of 2-oxo acid dehydrogenase complexes. Identification of these M2 mitochondrial autoantigens and detailed knowledge of their structure will allow important questions concerning this autoimmune disease to be addressed.<\/jats:p>","DOI":"10.1073\/pnas.85.22.8654","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T06:46:49Z","timestamp":1149058009000},"page":"8654-8658","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":198,"title":["Identification and analysis of the major M2 autoantigens in primary biliary cirrhosis."],"prefix":"10.1073","volume":"85","author":[{"given":"S P","family":"Fussey","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Medical School, University of Newcastle upon Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J R","family":"Guest","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical School, University of Newcastle upon Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O F","family":"James","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical School, University of Newcastle upon Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M F","family":"Bassendine","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical School, University of Newcastle upon Tyne, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S J","family":"Yeaman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical School, University of Newcastle upon Tyne, United Kingdom."}],"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.85.22.8654","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T12:45:00Z","timestamp":1649853900000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.85.22.8654"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1988,11]]},"references-count":0,"journal-issue":{"issue":"22","published-print":{"date-parts":[[1988,11]]}},"alternative-id":["10.1073\/pnas.85.22.8654"],"URL":"https:\/\/doi.org\/10.1073\/pnas.85.22.8654","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"}}]}}