{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T23:22:32Z","timestamp":1768000952174,"version":"3.49.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2012,4,20]],"date-time":"2012-04-20T00:00:00Z","timestamp":1334880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,4,20]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Although the hallmark of primary biliary cirrhosis (PBC) is the presence of anti-mitochondrial antibodies (AMA), a significant number of patients have anti-nuclear antibodies (ANA) directed primarily against two nuclear proteins, gp210 and sp100. In PBC, there are considerable data on the specificity of these anti-nuclear antibodies as well as suggestive evidence that antibodies to gp210 predict a poor outcome. However, a further understanding of the significance of these autoantibodies has been hampered by limitations in accessing human subjects in a preclinical or early asymptomatic stage. To overcome this limitation, we have taken advantage of transgenic mice with abrogated transforming growth factor-\u03b2 signalling in T cells (dnTGF-\u03b2RII) that develop histological features of PBC as well as the same AMA specificity. We studied these mice for serum ANA, including specific autoantibodies against gp210 and sp100. We further examined sera from dnTGF-\u03b2RII mice with concurrent deletions of the genes encoding interleukin (IL)-12p35, IL-12p40, IL-23p19, IL-17, IL-6, interferon (IFN)-\u03b3 or tumour necrosis factor (TNF)-\u03b1. Sera from all the dnTGF-\u03b2RII mouse lines contained antibodies against gp210 and sp100. Of significance, mice with germline deletions of the genes encoding IL-12p40, IL-23p19, IL-17, IL-6 and TNF-\u03b1 had significantly lower titres of anti-gp210 antibodies. These results provide a platform to dissect the mechanisms of gp210 and sp100 autoantibody production in dnTGF-\u03b2RII mice as well as to study the possible role of ANA in the pathophysiology of PBC.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2012.04577.x","type":"journal-article","created":{"date-parts":[[2012,2,20]],"date-time":"2012-02-20T23:47:06Z","timestamp":1329781626000},"page":"261-267","source":"Crossref","is-referenced-by-count":16,"title":["Epitope-specific anti-nuclear antibodies are expressed in a mouse model of primary biliary cirrhosis and are cytokine-dependent"],"prefix":"10.1093","volume":"168","author":[{"given":"C-Y","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P S C","family":"Leung","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G-X","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T P","family":"Kenny","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Coppel","sequence":"additional","affiliation":[{"name":"Department of Microbiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G L","family":"Norman","sequence":"additional","affiliation":[{"name":"INOVA Diagnostics, San Diego, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A A","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I R","family":"Mackay","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Monash University, Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H J","family":"Worman","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Pathology and Cell Biology, Columbia University, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M E","family":"Gershwin","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,4,20]]},"reference":[{"key":"2021122708381365000_b1","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1056\/NEJMra043898","article-title":"Primary biliary cirrhosis","volume":"353","author":"Kaplan","year":"2005","journal-title":"N Engl J Med"},{"key":"2021122708381365000_b2","volume-title":"The autoimmune diseases","author":"Rose","year":"2006","edition":"4th"},{"key":"2021122708381365000_b3","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S1568-9972(03)00013-2","article-title":"Antinuclear antibodies specific for primary biliary cirrhosis","volume":"2","author":"Worman","year":"2003","journal-title":"Autoimmun Rev"},{"key":"2021122708381365000_b4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0016-5085(90)91246-3","article-title":"Antinuclear antibodies directed to a 200-kilodalton polypeptide of the nuclear envelope in primary biliary cirrhosis. 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