{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:32:32Z","timestamp":1791271952727,"version":"4.1.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Norwegian PSC Research Center"},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research (NIHR)","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008538","name":"PSC Partners Seeking a Cure","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008538","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p>Hepatic T\u2010cell infiltrates and a strong genetic human leukocyte antigen association represent characteristic features of various immune\u2010mediated liver diseases. Conceptually the presence of disease\u2010associated antigens is predicted to be reflected in T\u2010cell receptor (TCR) repertoires. Here, we aimed to determine if disease\u2010associated TCRs could be identified in the nonviral chronic liver diseases primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and alcoholic liver disease (ALD). We performed high\u2010throughput sequencing of the TCR\u03b2 chain complementarity\u2010determining region 3 of liver\u2010infiltrating T cells from PSC (n\u2009=\u200920), PBC (n\u2009=\u200910), and ALD (n\u2009=\u200910) patients, alongside genomic human leukocyte antigen typing. The frequency of TCR\u03b2 nucleotide sequences was significantly higher in PSC samples (2.53\u2009\u00b1\u20090.80, mean\u2009\u00b1\u2009standard error of the mean) compared to PBC samples (1.13\u2009\u00b1\u20090.17, <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.0001) and ALD samples (0.62\u2009\u00b1\u20090.10, <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.0001). An average clonotype overlap of 0.85% was detected among PSC samples, significantly higher compared to the average overlap of 0.77% seen within the PBC (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.024) and ALD groups (0.40%, <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.0001). From eight to 42 clonotypes were uniquely detected in each of the three disease groups (\u226530% of the respective patient samples). Multiple, unique sequences using different variable family genes encoded the same amino acid clonotypes, providing additional support for antigen\u2010driven selection. In PSC and PBC, disease\u2010associated clonotypes were detected among patients with human leukocyte antigen susceptibility alleles. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: We demonstrate liver\u2010infiltrating disease\u2013associated clonotypes in all three diseases evaluated, and evidence for antigen\u2010driven clonal expansions. Our findings indicate that differential TCR signatures, as determined by high\u2010throughput sequencing, may represent an imprint of distinctive antigenic repertoires present in the different chronic liver diseases; this thereby opens up the prospect of studying disease\u2010relevant T cells in order to better understand and treat liver disease. (H<jats:sc>epatology<\/jats:sc> 2016;63:1608\u20101619)<\/jats:p>","DOI":"10.1002\/hep.28116","type":"journal-article","created":{"date-parts":[[2015,8,7]],"date-time":"2015-08-07T23:53:25Z","timestamp":1438991605000},"page":"1608-1619","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":75,"title":["High\u2010throughput T\u2010cell receptor sequencing across chronic liver diseases reveals distinct disease\u2010associated repertoires"],"prefix":"10.1097","volume":"63","author":[{"given":"Evaggelia","family":"Liaskou","sequence":"first","affiliation":[{"name":"Centre for Liver Research,National Institute for Health Research Birmingham Liver Biomedical Research Unit, University of Birmingham,Birmingham,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Kristine Klemsdal","family":"Henriksen","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery, and Transplantation,Oslo University Hospital Rikshospitalet,Oslo,Norway"},{"name":"Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery, and Transplantation, Oslo University Hospital, Rikshospitalet,Oslo,Norway"},{"name":"K.G. Jebsen Inflammation Research Centre,Institute of Clinical Medicine, University of Oslo,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Holm","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery, and Transplantation,Oslo University Hospital Rikshospitalet,Oslo,Norway"},{"name":"Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery, and Transplantation, Oslo University Hospital, Rikshospitalet,Oslo,Norway"},{"name":"K.G. Jebsen Inflammation Research Centre,Institute of Clinical Medicine, University of Oslo,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Kaveh","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics,Oslo University Hospital,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hamm","sequence":"additional","affiliation":[{"name":"Adaptive Biotechnologies Corp.,Seattle,WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Fear","sequence":"additional","affiliation":[{"name":"Centre for Liver Research,National Institute for Health Research Birmingham Liver Biomedical Research Unit, University of Birmingham,Birmingham,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marte K.","family":"Viken","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Oslo University Hospital Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes Roksund","family":"Hov","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery, and Transplantation,Oslo University Hospital Rikshospitalet,Oslo,Norway"},{"name":"Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery, and Transplantation, Oslo University Hospital, Rikshospitalet,Oslo,Norway"},{"name":"K.G. Jebsen Inflammation Research Centre,Institute of Clinical Medicine, University of Oslo,Oslo,Norway"},{"name":"Section of Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery, and Transplantation,Oslo University Hospital, Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Espen","family":"Melum","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery, and Transplantation,Oslo University Hospital Rikshospitalet,Oslo,Norway"},{"name":"Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery, and Transplantation, Oslo University Hospital, Rikshospitalet,Oslo,Norway"},{"name":"K.G. Jebsen Inflammation Research Centre,Institute of Clinical Medicine, University of Oslo,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harlan","family":"Robins","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center,Seattle,WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Olweus","sequence":"additional","affiliation":[{"name":"K.G. Jebsen Inflammation Research Centre,Institute of Clinical Medicine, University of Oslo,Oslo,Norway"},{"name":"Department of Immunology,Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet,Oslo,Norway"},{"name":"K.G. Jebsen Center for Cancer Immunotherapy,Institute of Clinical Medicine, University of Oslo,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom H.","family":"Karlsen","sequence":"additional","affiliation":[{"name":"Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery, and Transplantation,Oslo University Hospital Rikshospitalet,Oslo,Norway"},{"name":"Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery, and Transplantation, Oslo University Hospital, Rikshospitalet,Oslo,Norway"},{"name":"K.G. Jebsen Inflammation Research Centre,Institute of Clinical Medicine, University of Oslo,Oslo,Norway"},{"name":"Section of Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery, and Transplantation,Oslo University Hospital, Rikshospitalet,Oslo,Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon M.","family":"Hirschfield","sequence":"additional","affiliation":[{"name":"Centre for Liver Research,National Institute for Health Research Birmingham Liver Biomedical Research Unit, University of Birmingham,Birmingham,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,9,30]]},"reference":[{"key":"hep28116-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1002\/hep.1840010612","article-title":"Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative 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J"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.28116","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201605000-00027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:38Z","timestamp":1729209638000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201605000-00027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,30]]},"references-count":26,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.28116","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,30]]},"assertion":[{"value":"2015-03-31","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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