{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:00:10Z","timestamp":1791846010788,"version":"4.3.4"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Genetic predisposition to autoimmune hepatitis (AIH) in adults is associated\u00a0with possession of human leukocyte antigen (HLA) class I (<jats:italic toggle=\"yes\">A*01<\/jats:italic>,\u00a0<jats:italic toggle=\"yes\">B*08<\/jats:italic>) and class II (<jats:italic toggle=\"yes\">DRB1*03<\/jats:italic>,\u00a0<jats:italic toggle=\"yes\">\u201004<\/jats:italic>, \u2010<jats:italic toggle=\"yes\">07<\/jats:italic>, or\u00a0<jats:italic toggle=\"yes\">\u201013<\/jats:italic>) alleles,\u00a0depending on geographic region. Juvenile autoimmune liver disease (AILD) comprises AIH\u20101, AIH\u20102, and autoimmune sclerosing cholangitis (ASC), which are phenotypically different from their adult counterparts. We aimed to define the relationship between HLA profile and disease course, severity, and outcome in juvenile AILD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We studied 236 children of European ancestry (152 female [64%], median age 11.15 years, range 0.8\u201017), including 100 with AIH\u20101, 59 with AIH\u20102, and 77 with ASC. The follow\u2010up period was from 1977 to June 2019 (median 14.5 years). Class I and II HLA genotyping was performed using PCR\/sequence\u2010specific primers.\u00a0HLA\u00a0<jats:italic toggle=\"yes\">B*08<\/jats:italic>, \u2010<jats:italic toggle=\"yes\">DRB1*03<\/jats:italic>, and the\u00a0<jats:italic toggle=\"yes\">A1\u2010B8\u2010DR3<\/jats:italic>\u00a0haplotype impart predisposition to all three forms of AILD. Homozygosity for\u00a0<jats:italic toggle=\"yes\">DRB1*03<\/jats:italic>\u00a0represented the strongest risk factor (8.8). HLA\u00a0<jats:italic toggle=\"yes\">DRB1*04<\/jats:italic>,\u00a0which independently confers susceptibility to AIH in adults, was infrequent in AIH\u20101 and ASC, suggesting protection; and <jats:italic toggle=\"yes\">DRB1*15<\/jats:italic> (DR15)\u00a0was protective against all forms of AILD. Distinct HLA class II alleles predispose to the different subgroups of juvenile AILD:\u00a0<jats:italic toggle=\"yes\">DRB1*03<\/jats:italic>\u00a0to AIH\u20101,\u00a0<jats:italic toggle=\"yes\">DRB1*13<\/jats:italic>\u00a0to ASC, and\u00a0<jats:italic toggle=\"yes\">DRB1*07<\/jats:italic>\u00a0to AIH\u20102. Possession of homozygous\u00a0<jats:italic toggle=\"yes\">DRB1*03<\/jats:italic> or of <jats:italic toggle=\"yes\">DRB1*13<\/jats:italic> is\u00a0associated with fibrosis at disease onset, and possession of these two genes in addition to\u00a0<jats:italic toggle=\"yes\">DRB1*07<\/jats:italic>\u00a0is associated with a more severe disease in all three subgroups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Unique HLA profiles are seen in each subgroup of juvenile AILD. HLA genotype might be useful in predicting\u00a0responsiveness to immunosuppressive treatment and course.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31893","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T15:09:51Z","timestamp":1620659391000},"page":"2032-2046","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":47,"title":["Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry"],"prefix":"10.1097","volume":"74","author":[{"given":"Yun","family":"Ma","sequence":"first","affiliation":[{"name":"Institute of Liver Studies,MowatLabs,Department of Inflammation Biology,School of Immunology & Microbial Sciences,Faculty of Life Sciences and Medicine,King\u2019s College London,London,United 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Serena","family":"Longhi","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,MowatLabs,Department of Inflammation Biology,School of Immunology & Microbial Sciences,Faculty of Life Sciences and Medicine,King\u2019s College London,London,United Kingdom"},{"name":"Department of Anesthesia,Beth Israel Deaconess Medical Center,Harvard Medical School,Boston,MA,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"McPhail","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,MowatLabs,Department of Inflammation Biology,School of Immunology & Microbial Sciences,Faculty of Life Sciences and Medicine,King\u2019s College London,London,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,MowatLabs,Department of Inflammation Biology,School of Immunology & Microbial Sciences,Faculty of Life 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Inflammation Biology,School of Immunology & Microbial Sciences,Faculty of Life Sciences and Medicine,King\u2019s College London,London,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3821-9342","authenticated-orcid":false,"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology,West China Hospital,Sichuan University,Chengdu,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"J Thompson","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,MowatLabs,Department of Inflammation Biology,School of Immunology & Microbial Sciences,Faculty of Life Sciences and Medicine,King\u2019s College London,London,United Kingdom"},{"name":"Paediatric Liver, GI and Nutrition Centre,King\u2019s College Hospital,London,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek G.","family":"Doherty","sequence":"additional","affiliation":[{"name":"Discipline of Immunology,School of Medicine,Trinity College Dublin,Dublin,Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nedim","family":"Hadzic","sequence":"additional","affiliation":[{"name":"Paediatric Liver, GI and Nutrition Centre,King\u2019s College Hospital,London,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoh","family":"Zen","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,MowatLabs,Department of Inflammation Biology,School of Immunology & Microbial Sciences,Faculty of Life Sciences and Medicine,King\u2019s College London,London,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Quaglia","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,MowatLabs,Department of Inflammation Biology,School of Immunology & Microbial Sciences,Faculty of Life Sciences 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