{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T09:34:21Z","timestamp":1717580061907},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,9,8]],"date-time":"2011-09-08T00:00:00Z","timestamp":1315440000000},"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":[[2012,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Recently, a non\u2010M2\u2010related mitochondrial 60\u00a0kDa protein found to be recognized by antimitochondrial antibody (<jats:styled-content style=\"fixed-case\">AMA<\/jats:styled-content>) negative sera from patients with primary biliary cirrhosis (<jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>) has been shown to contain parts of the five F<jats:sub>1<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase subunits \u03b1, \u03b2, \u03b3, \u03b4 and \u03b5. In this study, we examined whether this enzyme is, indeed, a target antigen in <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Analysed were 60 <jats:styled-content style=\"fixed-case\">AMA<\/jats:styled-content>\u2010positive\/anti\u2010M2\u2010negative and 103 anti\u2010M2\u2010positive <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content> patients, 46 patients with autoimmune hepatitis (<jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content>), 35 patients with primary sclerosing cholangitis (<jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content>), 110 patients with viral hepatitis, 40 patients with inflammatory bowel diseases (<jats:styled-content style=\"fixed-case\">IBD<\/jats:styled-content>), 33 patients with connective tissue diseases (systemic lupus erythematosus, mixed connective tissue disease, <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>j\u00f6gren disease, systemic sclerosis) and 25 blood donors. The F<jats:sub>1<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase\u2010subunits \u03b1\u2010\u03b4 were recombinantly expressed in <jats:styled-content style=\"fixed-case\"><jats:italic>E<\/jats:italic><\/jats:styled-content><jats:italic>scherichia\u00a0coli<\/jats:italic>, purified and applied to <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>estern blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In all, 40 of the 60 <jats:styled-content style=\"fixed-case\">AMA<\/jats:styled-content>\u2010positive\/anti\u2010M2\u2010negative (67%) and 44 (43%) of the 103 anti\u2010M2\u2010positive <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>\u2010sera reacted with at least one of the F<jats:sub>1<\/jats:sub>\u2010subunits \u03b1\u2010\u03b4. The \u03b2\u2010 and \u03b3\u2010subunits were preferentially recognized. However, also up to 57% of patients with <jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content> and 34% of patients with <jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content> had anti\u2010\u03b2\u2010 or \u03b3\u2010antibodies, while patients with viral hepatitis had these antibodies in up to 13%. Patients with <jats:styled-content style=\"fixed-case\">IBD<\/jats:styled-content> had anti\u2010\u03b2 and anti\u2010\u03b3\u2010antibodies in up to 20 and 5% respectively. None of the patients with connective tissue diseases had antibodies to the \u03b2\u2010 and only 6% to the \u03b3\u2010subunit. Sera from healthy blood donors were negative.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Antibodies to the \u03b2\u2010 and \u03b3\u2010subunits of F<jats:sub>1<\/jats:sub>\u2010<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase are further <jats:styled-content style=\"fixed-case\">AMA<\/jats:styled-content>s in <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content> but occur also in other autoimmune liver disorders; they may be, therefore, indicators for a general autoimmune process of the liver.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1478-3231.2011.02630.x","type":"journal-article","created":{"date-parts":[[2011,9,8]],"date-time":"2011-09-08T13:36:23Z","timestamp":1315488983000},"page":"249-257","source":"Crossref","is-referenced-by-count":6,"title":["Relevance of the inner mitochondrial membrane enzyme F<sub>1<\/sub>F<sub>0<\/sub>\u2010<scp>ATP<\/scp>ase as an autoantigen in autoimmune liver disorders"],"prefix":"10.1111","volume":"32","author":[{"given":"Beate","family":"Preu\u00df","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II University of T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Berg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University of T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rn","family":"Dengjel","sequence":"additional","affiliation":[{"name":"Department of Immunology Institute for Cell Biology University of T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Stevanovic","sequence":"additional","affiliation":[{"name":"Department of Immunology Institute for Cell Biology University of T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhild","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University of T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,9,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840080146"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0770365"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.4049\/jimmunol.138.10.3525","article-title":"Identification and specificity of a cDNA encoding the 70kD mitochondrial antigen recognized in primary biliary cirrhosis","volume":"138","author":"Gershwin ME","year":"1987","journal-title":"J Immunol"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840050510"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(88)91894-6"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.164335"},{"key":"e_1_2_7_8_1","first-page":"1000A","article-title":"Identification of the \u03b2\u2010 and \u03b3\u2010subunits of F1\u2010ATPase as target antigens in anti\u2010M2\/PDC\u2010E2 negative primary biliary cirrhosis","volume":"50","author":"Preu\u00df B","year":"2009","journal-title":"Hepatology"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0070213"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1040734"},{"key":"e_1_2_7_11_1","first-page":"68","article-title":"Heterogeneity of antimitochondrial antibodies: characterization and separation of the antigen associated with the pseudolupus erythematosus syndrome","volume":"37","author":"Sayers TJ","year":"1979","journal-title":"Clin Exp Immunol"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00743204"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.78.081307.104803"},{"key":"e_1_2_7_14_1","unstructured":"GoodsellDS.Molecule of the month.2005. 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