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Ma Y, Su H, Yuksel M, et al. Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry. Hepatology. 2021;74(4):2032-2046doi: 10.1002/hep.31893.
Ma, Y., Su, H., Yuksel, M., Longhi, M. S., McPhail, M. J., Wang, P., Bansal, S., Wong, G. W., Graham, J., Yang, L., J Thompson, R., Doherty, D. G., Hadzic, N., Zen, Y., Quaglia, A., Heneghan, M. A., Samyn, M., Vergani, D., & Mieli-Vergani, G. (2021). Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry. Hepatology (Baltimore, Md.), 74(4), 2032-2046. https://doi.org/10.1002/hep.31893
Ma, Yun, et al. "Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry." Hepatology (Baltimore, Md.) vol. 74,4 (2021): 2032-2046. doi: https://doi.org/10.1002/hep.31893
Ma 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. Hepatology. 2021 Oct;74(4):2032-2046. doi: 10.1002/hep.31893. Epub 2021 Jun 21. PMID: 33971035; PMCID: PMC8463472.
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Hepatology. 2021 Oct;74(4):2032-2046. doi: 10.1002/hep.31893. Epub 2021 Jun 21.

Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry.

Hepatology (Baltimore, Md.)

Yun Ma, Haibin Su, Muhammed Yuksel, Maria Serena Longhi, Mark J McPhail, Pengyun Wang, Sanjay Bansal, Guan-Wee Wong, Jonathon Graham, Li Yang, Richard J Thompson, Derek G Doherty, Nedim Hadzic, Yoh Zen, Alberto Quaglia, Michael A Heneghan, Marianne Samyn, Diego Vergani, Giorgina Mieli-Vergani

Affiliations

  1. Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
  2. Department of Liver Disease of Chinese PLA General Hospital, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  3. Koc University Research Centre for Translational Medicine, Istanbul, Turkey.
  4. Department of Anesthesia, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  5. Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, United Kingdom.
  6. Department of Medicine, Ng Teng Fong General Hospital, Singapore.
  7. Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, China.
  8. Discipline of Immunology, School of Medicine, Trinity College Dublin, Dublin, Ireland.
  9. Department of Cellular Pathology, Royal Free London NHS Foundation Trust, UCL Cancer Institute, Research Department of Pathology, London, United Kingdom.

PMID: 33971035 PMCID: PMC8463472 DOI: 10.1002/hep.31893

Abstract

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.

© 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.

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