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

Ma, Yun, Su, Haibin, Yuksel, Muhammed, 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 and Mieli-Vergani, Giorgina 2021. Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry. Hepatology. 74 (4), pp. 2032-2046. https://doi.org/10.1002/hep.31893

TitleHuman Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry
TypeJournal article
AuthorsMa, Yun, Su, Haibin, Yuksel, Muhammed, 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 and Mieli-Vergani, Giorgina
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.

JournalHepatology
Journal citation74 (4), pp. 2032-2046
ISSN0270-9139
1527-3350
Year2021
PublisherAmerican Association for the Study of Liver Diseases
Wiley
Publisher's version
License
CC BY 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1002/hep.31893
Publication dates
PublishedOct 2021

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