{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T05:46:38Z","timestamp":1697175998871},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2006,6,26]],"date-time":"2006-06-26T00:00:00Z","timestamp":1151280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:p><jats:bold>Abstract: Background: <\/jats:bold> Primary biliary cirrhosis (PBC) is characterized by the presence of antimitochondrial antibodies (AMA). Autoantibodies specific for the mitochondrial M4 antigen can be detected by a complement fixation test (CFT) but not by immunoblotting. The aim of this study was to elucidate the identity of the M4 antigen.<\/jats:p><jats:p><jats:bold>Patients and methods: <\/jats:bold> M4 proteins were purified by affinity chromatography using IgG fractions of PBC marker sera being CFT positive (<jats:italic>n<\/jats:italic>=5) or negative (<jats:italic>n<\/jats:italic>=5) and identified by Western blotting, silver staining and sequence analysis. Further, a cohort of 57 PBC patients was tested for the reactivity to M4 and pyruvate dehydrogenase complex (PDC).<\/jats:p><jats:p><jats:bold>Results: <\/jats:bold> Two AMA patterns of the marker sera were visualized: CFT\u2010positive sera were defined as PDC\u2010E2<jats:sup>+<\/jats:sup>\/E1<jats:sup>+<\/jats:sup> and the CFT\u2010negative sera as PDC\u2010E2<jats:sup>+<\/jats:sup>\/E1<jats:sup>\u2212<\/jats:sup>. The major proteins in the M4 fraction could be related to the PDC\u2010E1 subunits. A clear\u2010cut association between anti\u2010M4 reactivity in the CFT and the reactivity to both PDC subunits could also be documented in the cohort of 57 PBC patients showing anti\u2010PDC\u2010E1\u03b1 and E1\u03b2 antibodies at a frequency of 74% and 67%.<\/jats:p><jats:p><jats:bold>Conclusions: <\/jats:bold> CFT reactivity against M4 antigens could be preferentially identified as a reaction against PDC\u2010E1. As PDC\u2010E1 subunits as compared with PDC\u2010E2 lack lipoyl\u2010binding sites, they probably have to be considered as an independent and important target.<\/jats:p>","DOI":"10.1111\/j.1478-3231.2006.01303.x","type":"journal-article","created":{"date-parts":[[2006,6,26]],"date-time":"2006-06-26T12:12:39Z","timestamp":1151323959000},"page":"846-855","source":"Crossref","is-referenced-by-count":7,"title":["Demonstration of PDC\u2010E1 subunits as major antigens in the complement\u2010fixing fraction M4 and re\u2010evaluation of PDC\u2010E1\u2010specific antibodies in PBC patients"],"prefix":"10.1111","volume":"26","author":[{"given":"Christoph P.","family":"Berg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerburg M.","family":"Stein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhild","family":"Klein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Pascu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Berg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winfried","family":"Kammer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Priemer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfred","family":"Nordheim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Schulze\u2010Osthoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Gregor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Wesselborg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Berg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,6,28]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197309272891306"},{"key":"e_1_2_7_3_2","first-page":"213","volume-title":"Molecular Analysis of Cytoplasmic Autoantigens in Liver Disease","author":"Gershwin E M.","year":"1992"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0770365"},{"key":"e_1_2_7_5_2","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.4049\/jimmunol.144.5.1671","article-title":"Primary biliary cirrhosis. 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