HLA-DRB1∗03:01 and HLA-DRB1∗04:01 modify the presentation and outcome in autoimmune hepatitis type-1
Genes and Immunity , Volume 16 - Issue 4 p. 247- 252
The classical human leukocyte antigen (HLA)-DRB103:01 and HLA-DRB104:01 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-DRB103:01/HLA-DRB104:01 positive. HLA-DRB103:01/HLA-DRB104:01-positive patients had a higher median IAIHG score than HLA-DRB103:01/HLA-DRB104:01-negative patients (P<0.001). We did not observe associations between HLA alleles and alanine transaminase levels (HLA-DRB103:01: P=0.2; HLA-DRB104:01; P=0.5); however, HLA-DRB103:01 was independently associated with higher immunoglobulin G levels (P=0.04). The HLA-DRB104:01 allele was independently associated with presentation at older age (P=0.03) and a female predominance (P=0.04). HLA-DRB103:01-positive patients received immunosuppressive medication and liver transplantation. In conclusion, the HLA-DRB103:01 and HLA-DRB104:01 alleles are both independently associated with the aggregate diagnostic IAIHG score in type-1 AIH patients, but are not essential for AIH development. HLA-DRB103:01 is the strongest genetic modifier of disease severity in AIH.
|Genes and Immunity|
|Organisation||Department of Gastroenterology & Hepatology|
van Gerven, N.M.F, de Boer, Y.S, Zwiers, A, Verwer, B.J, Drenth, J.P.H, van Hoek, B, … Verhagen, M.A.M.T. (2015). HLA-DRB1∗03:01 and HLA-DRB1∗04:01 modify the presentation and outcome in autoimmune hepatitis type-1. Genes and Immunity, 16(4), 247–252. doi:10.1038/gene.2014.82