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dc.contributor.authorDoherty, Derek
dc.date.accessioned2022-02-23T07:36:13Z
dc.date.available2022-02-23T07:36:13Z
dc.date.issued2021
dc.date.submitted2021en
dc.identifier.citationMa Y, Su H, Yuksel M, Longhi MS, McPhail MJ, Wang P, Bansal S, Wong GW, Graham J, Yang L, J Thompson R, Doherty DG, Hadzic N, Zen Y, Quaglia A, Heneghan MA, Samyn M, Vergani D, Mieli-Vergani G, Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry, 2021, 74, 4, 2032-2046en
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/98158
dc.descriptionPUBLISHEDen
dc.description.abstractBackground and aims: Genetic predisposition to autoimmune hepatitis (AIH) in adults is associated with possession of human leukocyte antigen (HLA) class I (A*01, B*08) and class II (DRB1*03, -04, -07, or -13) alleles, depending on geographic region. Juvenile autoimmune liver disease (AILD) comprises AIH-1, AIH-2, 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. Approach and results: We studied 236 children of European ancestry (152 female [64%], median age 11.15 years, range 0.8-17), including 100 with AIH-1, 59 with AIH-2, and 77 with ASC. The follow-up period was from 1977 to June 2019 (median 14.5 years). Class I and II HLA genotyping was performed using PCR/sequence-specific primers. HLA B*08, -DRB1*03, and the A1-B8-DR3 haplotype impart predisposition to all three forms of AILD. Homozygosity for DRB1*03 represented the strongest risk factor (8.8). HLA DRB1*04, which independently confers susceptibility to AIH in adults, was infrequent in AIH-1 and ASC, suggesting protection; and DRB1*15 (DR15) was protective against all forms of AILD. Distinct HLA class II alleles predispose to the different subgroups of juvenile AILD: DRB1*03 to AIH-1, DRB1*13 to ASC, and DRB1*07 to AIH-2. Possession of homozygous DRB1*03 or of DRB1*13 is associated with fibrosis at disease onset, and possession of these two genes in addition to DRB1*07 is associated with a more severe disease in all three subgroups. Conclusions: Unique HLA profiles are seen in each subgroup of juvenile AILD. HLA genotype might be useful in predicting responsiveness to immunosuppressive treatment and course.en
dc.format.extent2032-2046en
dc.language.isoenen
dc.relation.ispartofseries74;
dc.relation.ispartofseries4;
dc.rightsYen
dc.titleHuman Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestryen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/dohertde
dc.identifier.rssinternalid238581
dc.identifier.doi10.1002/hep.31893en
dc.rights.ecaccessrightsopenAccess
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.identifier.orcid_id0000-0002-4394-658X


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