{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T10:26:30Z","timestamp":1772792790584,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,3,11]],"date-time":"2014-03-11T00:00:00Z","timestamp":1394496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["MOP86506"],"award-info":[{"award-number":["MOP86506"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000264","name":"Canadian Liver Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000264","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000010","name":"Canadian Association for the Study of the Liver","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000010","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001424","name":"American Liver foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001424","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Some patients with autoimmune hepatitis (<jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content>), despite appropriate treatment, progress towards cirrhosis and liver failure, requiring transplantation. New biological agents targeting immune cell subtypes have been developed, with better specificity and longer\u2010lasting effects than conventional wide\u2010spectrum immunosuppressive drugs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>The goal of this study was to evaluate the effectiveness of low dose of \u03b1<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>3 targeting therapy in a model of type 2 <jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This experimental model is based on xenoimmunization of C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice with <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> coding for human liver autoantigens. Mice with <jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content> were treated with five daily injections of low dose of \u03b1<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>3 monoclonal antibody, before disease onset (5.5\u00a0months post\u2010xenoimmunization) or during <jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content> (7\u00a0months post\u2010xenoimmunization). Along with serum aminotransferases, autoantibody levels and end\u2010point liver histology, spleen and liver\u2010infiltrating lymphocytes were phenotyped by flow cytometry and immune response measured by lymphoproliferative assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Before onset of <jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content>, treatment prevented the development of liver inflammation and tissue injury. During active <jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content>, low dose of \u03b1<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>3 antibody therapy resulted in a resorption of liver inflammatory infiltrates, normalization of serum aminotransferas levels, reduced autoantibody titres, increased regulatory T\u00a0cells and lowered proliferation of autoreactive liver lymphocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We report that low dose \u03b1<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>3 antibody administration is an effective treatment for <jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content> in an experimental model of type 2 <jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content>. These data suggest that \u03b1<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>3 antibody therapy could be tested in clinical trials as a rescue therapy for patients with uncontrolled <jats:styled-content style=\"fixed-case\">AIH<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12498","type":"journal-article","created":{"date-parts":[[2014,2,12]],"date-time":"2014-02-12T11:51:49Z","timestamp":1392205909000},"page":"275-284","source":"Crossref","is-referenced-by-count":15,"title":["Low\u2010dose anti\u2010<scp>CD<\/scp>3 antibody induces remission of active autoimmune hepatitis in xenoimmunized mice"],"prefix":"10.1111","volume":"35","author":[{"given":"Gabriel","family":"Marceau","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology &amp; Nutrition CHU Sainte\u2010Justine Montr\u00e9al QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology &amp; Nutrition CHU Sainte\u2010Justine Montr\u00e9al QC Canada"},{"name":"Department of Microbiology &amp; Immunology University of Montr\u00e9al Montr\u00e9al QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Lapierre","sequence":"additional","affiliation":[{"name":"INRS \u2013 Institut Armand\u2010Frappier Laval QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathie","family":"B\u00e9land","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology &amp; Nutrition CHU Sainte\u2010Justine Montr\u00e9al QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology &amp; Nutrition CHU Sainte\u2010Justine Montr\u00e9al QC Canada"},{"name":"Department of Microbiology &amp; Immunology University of Montr\u00e9al Montr\u00e9al QC Canada"},{"name":"Department of Pediatrics Faculty of Medicine University of Montr\u00e9al Montr\u00e9al QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,3,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23584"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2010.10.013"},{"key":"e_1_2_7_4_1","first-page":"429","volume-title":"Liver disease in childhood","author":"Alvarez F","year":"2001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050408"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1000"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.1.123"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.8.3434"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2006.09.004"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043980"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2009.04.007"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2011.08.004"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.04.053"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20109"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2005.11.001"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23536"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26023"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2005.01107.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.34944"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2011.07.009"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.2165\/11586290-000000000-00000"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.11.010"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-204875"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012864"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60931-8"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.6.1763"},{"key":"e_1_2_7_27_1","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1182\/blood.V89.4.1357","article-title":"Role of Fas ligand and receptor in the mechanism of T\u2010cell depletion in acquired immunodeficiency syndrome: effect on CD4+ lymphocyte depletion and human immunodeficiency virus replication","volume":"89","author":"Sloand EM","year":"1997","journal-title":"Blood"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.70.5.756"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2010.08.004"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.158.6.2947"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e318154af74"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.42.5.721"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm924"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.275"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2006.00428.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.933"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1644-9"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60886-6"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0904452"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12498","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12498","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.12498","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T14:27:42Z","timestamp":1695479262000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.12498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,11]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1111\/liv.12498"],"URL":"https:\/\/doi.org\/10.1111\/liv.12498","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,11]]}}}