Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry
| العنوان: | Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry |
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| المؤلفون: | Maria Serena Longhi, Marianne Samyn, Guan-Wee Wong, Nedim Hadzic, Yoh Zen, Li Yang, Mark J. W. McPhail, Diego Vergani, Giorgina Mieli-Vergani, Muhammed Yuksel, Jonathon Graham, Derek G. Doherty, Sanjay Bansal, Michael A. Heneghan, Richard J. Thompson, Haibin Su, Pengyun Wang, Alberto Quaglia, Yun Ma |
| المساهمون: | Yüksel, Muhammed, Ma, Yun, Su, Haibin, Longhi, Maria Serena, McPhail, Mark J., Wang, Pengyun, Bansal, Sanjay, Wong, Guan-Wee, Graham, Jonathon, Yang, Li, Thompson, Richard J., Doherty, Derek G., Hadzic, Nedim, Zen, Yoh, Quaglia, Alberto, Heneghan, Michael A., Samyn, Marianne, Vergani, Diego, Mieli-Vergani, Giorgina, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM) |
| المصدر: | Hepatology |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, musculoskeletal diseases, 0301 basic medicine, Adolescent, Gastroenterology and hepatology, Class II region, HLA-DRB1 alleles, Overlap syndrome, Hepatitis, HLA, Susceptibility, Protection, Diagnosis, Immunogenetics, Cholangitis, Sclerosing, Human leukocyte antigen, Autoimmune hepatitis, medicine.disease_cause, Severity of Illness Index, White People, Article, HLA-B8 Antigen, Autoimmunity, 03 medical and health sciences, HLA-DR3 Antigen, 0302 clinical medicine, HLA Antigens, immune system diseases, Genetic predisposition, Humans, Medicine, Genetic Predisposition to Disease, Allele, Risk factor, Child, HLA-A1 Antigen, Hepatology, business.industry, Infant, medicine.disease, Hepatitis, Autoimmune, 030104 developmental biology, Child, Preschool, Immunology, Female, 030211 gastroenterology & hepatology, business, HLA-DRB1 Chains |
| الوصف: | Background 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. Fifth Medical Center of PLA General Hospital; Roger Dobson Funds; King's College Hospital Charity; Medical Research Council Clinician Scientist Fellowship; Medical Research Council PhD Studentship; Alex Mowat PhD Studentship; King's College Hospital Charity; National Institute for Health Research University College London Hospital/University College London Biomedical Research Centre |
| وصف الملف: | |
| تدمد: | 1527-3350 0270-9139 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8b9f7f048035297834b884494f867404Test https://doi.org/10.1002/hep.31893Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8b9f7f048035297834b884494f867404 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15273350 02709139 |
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