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Genes Immun. 2015 Jun;16(4):247-52. doi: 10.1038/gene.2014.82. Epub 2015 Jan 22.

HLA-DRB1*03:01 and HLA-DRB1*04:01 modify the presentation and outcome in autoimmune hepatitis type-1.

Author information

1
Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
2
1] Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands [2] Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
3
Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
4
Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
5
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
6
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
7
Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
8
Department of Gastroenterology and Hepatology, Haga Hospital, The Hague, The Netherlands.
9
1] University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, The Netherlands [2] Department of Gastroenterology and Hepatology, St Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands.
10
Department of Gastroenterology and Hepatology, University Medical Center Maastricht, Maastricht, The Netherlands.
11
Department of Gastroenterology and Hepatology, Reinier de Graaf Hospital, Delft, The Netherlands.
12
Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, Enschede, The Netherlands.
13
Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, The Netherlands.
14
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
15
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
16
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.

Abstract

The classical human leukocyte antigen (HLA)-DRB1*03:01 and HLA-DRB1*04:01 alleles are established autoimmune hepatitis (AIH) risk alleles. To study the immune-modifying effect of these alleles, we imputed the genotypes from genome-wide association data in 649 Dutch AIH type-1 patients. We therefore compared the international AIH group (IAIHG) diagnostic scores as well as the underlying clinical characteristics between patients positive and negative for these HLA alleles. Seventy-five percent of the AIH patients were HLA-DRB1*03:01/HLA-DRB1*04:01 positive. HLA-DRB1*03:01/HLA-DRB1*04:01-positive patients had a higher median IAIHG score than HLA-DRB1*03:01/HLA-DRB1*04:01-negative patients (P<0.001). We did not observe associations between HLA alleles and alanine transaminase levels (HLA-DRB1*03:01: P=0.2; HLA-DRB1*04:01; P=0.5); however, HLA-DRB1*03:01 was independently associated with higher immunoglobulin G levels (P=0.04). The HLA-DRB1*04:01 allele was independently associated with presentation at older age (P=0.03) and a female predominance (P=0.04). HLA-DRB1*03:01-positive patients received immunosuppressive medication and liver transplantation. In conclusion, the HLA-DRB1*03:01 and HLA-DRB1*04:01 alleles are both independently associated with the aggregate diagnostic IAIHG score in type-1 AIH patients, but are not essential for AIH development. HLA-DRB1*03:01 is the strongest genetic modifier of disease severity in AIH.

PMID:
25611558
DOI:
10.1038/gene.2014.82
[Indexed for MEDLINE]

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