{"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":1791846010344,"version":"4.3.4"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The strongest genetic association with autoimmunity is within chromosome 6p21, where the human leukocyte antigen (HLA) complex resides. This review will focus on the HLA associations within pediatric autoimmune hepatitis, autoimmune sclerosing cholangitis and primary sclerosing cholangitis. In general, there is considerable overlap in HLA genotypes conferring susceptibility to pediatric autoimmune liver diseases, however unique HLA associations and protective HLA genotypes exist. There are numerous areas for future research initiatives in pediatric autoimmune liver diseases and HLA associations with clinical outcomes, autoantigen discovery and novel therapeutics targeting the HLA- autoantigen- T cell pathway will be highlighted.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1019339","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T10:08:04Z","timestamp":1664446084000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["HLA Associations in pediatric autoimmune liver diseases: Current state and future research initiatives"],"prefix":"10.3389","volume":"13","author":[{"given":"Cara L.","family":"Mack","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00707-2","article-title":"A guide to antigen processing and presentation","author":"Pishesha","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.932086","article-title":"From disease and patient heterogeneity to precision medicine in type 1 diabetes","volume":"9","author":"den Hollander","year":"2022","journal-title":"Front Med (Lausanne)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/bs.ircmb.2020.09.009","article-title":"The HLA complex and coeliac disease","volume":"358","author":"Espino","year":"2021","journal-title":"Int Rev Cell Mol Biol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.jaut.2018.10.007","article-title":"Juvenile autoimmune hepatitis: A comprehensive review","volume":"95","author":"Sokollik","year":"2018","journal-title":"J Autoimmun"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2021.104214","article-title":"Genetic aspects of adult and pediatric autoimmune hepatitis: A concise review","volume":"64","author":"Engel","year":"2021","journal-title":"Eur J Med Genet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00768-8","article-title":"Autoimmmune hepatitis","volume":"19","author":"Terziroli Beretta-Piccoli","year":"2022","journal-title":"Cell Mol Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31893","article-title":"Human leukocyte antigen profile predicts severity of autoimmune liver disease in children of European ancestry","volume":"74","author":"Ma","year":"2021","journal-title":"Hepatology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1002\/lt.22244","article-title":"Outcomes in children who underwent transplantation for autoimmune hepatitis","volume":"17","author":"Martin","year":"2011","journal-title":"Liver Transpl"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-015-2662-x","article-title":"Human leucocyte antigens and pediatric autoimmune liver disease: Diagnosis and prognosis","volume":"175","author":"Junge","year":"2016","journal-title":"Eur J Pediatr"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1590\/S0004-2803.201900000-29","article-title":"HLA-DRB1 gene polymorphisms in pediatric patients with type 1 autoimmune hepatitis and type 1 autoimmune hepatitis overlap syndrome with autoimmune cholangitis","volume":"56","author":"Nunes","year":"2019","journal-title":"Arq Gastroenterol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300611","article-title":"Pediatric and adult forms of type I autoimmune hepatitis in Argentina: Evidence for differential genetic predisposition","volume":"30","author":"Pando","year":"1999","journal-title":"Hepatology"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.07.022","article-title":"Primary sclerosing cholangitis - a comprehensive review","volume":"67","author":"Karlsen","year":"2017","journal-title":"J Hepatol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e114486","DOI":"10.1371\/journal.pone.0114486","article-title":"Refinement of the MHC risk map in a scandinavian primary sclerosing cholangitis population","volume":"9","author":"N\u00e6ss","year":"2014","journal-title":"PLoS One"},{"key":"B14","article-title":"Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis","volume":"22","author":"Wilschanski","year":"1995","journal-title":"Hepatology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/gut.51.4.609","article-title":"Susceptibility to primary sclerosing cholangitis in Brazil is associated with HLA-DRB1*13 but not with tumour necrosis factor alpha -308 promoter polymorphism","volume":"51","author":"Bittencourt","year":"2002","journal-title":"Gut"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/apa.13641","article-title":"Human leucocyte antigens B*08, DRB1*03 and DRB1*13 are significantly associated with autoimmune liver and biliary diseases in Finnish children","volume":"106","author":"Ylinen","year":"2017","journal-title":"Acta Paediatr"},{"key":"B17","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1136\/gut.2003.031732","article-title":"Genetics of liver disease: Immunogenetics and disease pathogenesis","volume":"53","author":"Donaldson","year":"2004","journal-title":"Gut"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-35705","article-title":"Genetics in autoimmune hepatitis","volume":"22","author":"Donaldson","year":"2002","journal-title":"Semin Liver Dis"},{"key":"B19","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1053\/j.gastro.2014.04.022","article-title":"Genome-wide association study identifies variants associated with autoimmune hepatitis type 1","volume":"147","author":"de Boer","year":"2014","journal-title":"Gastroenterology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1002\/cld.830","article-title":"Autoimmune hepatitis in special populations: In pediatrics and across different Ethnicities\/Races","volume":"14","author":"Kerkar","year":"2019","journal-title":"Clin Liver Dis (Hoboken)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.12.020","article-title":"Polyclonal T-cell responses to cytochrome P450IID6 are associated with disease activity in autoimmune hepatitis type 2","volume":"130","author":"Ma","year":"2006","journal-title":"Gastroenterology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21658","article-title":"Cytochrome P450IID6-specific CD8 T cell immune responses mirror disease activity in autoimmune hepatitis type 2","volume":"46","author":"Longhi","year":"2007","journal-title":"Hepatology"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2003.09.009","article-title":"Characterization of the antigenicity of the formiminotransferase-cyclodeaminase in type 2 autoimmune hepatitis","volume":"292","author":"Renous","year":"2004","journal-title":"Exp Cell Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.ajpath.2021.10.006","article-title":"Development of a new murine model of type 2 autoimmune hepatitis using a human liver protein","volume":"192","author":"Thomas-Dupont","year":"2022","journal-title":"Am J Pathol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbac076","article-title":"HLA3D: An integrated structure-based computational toolkit for immunotherapy","volume":"23","author":"Li","year":"2022","journal-title":"Brief Bioinform"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.1038\/s41467-019-09893-5","article-title":"Suppression of a broad spectrum of liver autoimmune pathologies by single peptide-MHC-based nanomedicines","volume":"10","author":"Umeshappa","year":"2019","journal-title":"Nat Commun"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-022-00940-w","article-title":"Challenges and opportunities in achieving effective regulatory T cell therapy in autoimmune liver disease","volume":"44","author":"Richardson","year":"2022","journal-title":"Semin Immunopathol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1019339\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T13:36:48Z","timestamp":1665668208000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1019339\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,29]]},"references-count":27,"alternative-id":["10.3389\/fimmu.2022.1019339"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1019339","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,29]]},"article-number":"1019339"}}