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

Autor: van Gerven NM; Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands., de Boer YS; Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands., Zwiers A; 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., Verwer BJ; Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands., Drenth JP; Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands., van Hoek B; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands., van Erpecum KJ; Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands., Beuers U; Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands., van Buuren HR; Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands., den Ouden JW; Department of Gastroenterology and Hepatology, Haga Hospital, The Hague, The Netherlands., Verdonk RC; 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., Koek GH; Department of Gastroenterology and Hepatology, University Medical Center Maastricht, Maastricht, The Netherlands., Brouwer JT; Department of Gastroenterology and Hepatology, Reinier de Graaf Hospital, Delft, The Netherlands., Guichelaar MM; Department of Gastroenterology and Hepatology, Medisch Spectrum Twente, Enschede, The Netherlands., Vrolijk JM; Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, The Netherlands., Coenraad MJ; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands., Kraal G; Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands., Mulder CJ; Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands., van Nieuwkerk CM; Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands., Bloemena E; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands., Verspaget HW; Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands., Kumar V; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands., Zhernakova A; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands., Wijmenga C; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands., Franke L; University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands., Bouma G; 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.
Jazyk: angličtina
Zdroj: Genes and immunity [Genes Immun] 2015 Jun; Vol. 16 (4), pp. 247-52. Date of Electronic Publication: 2015 Jan 22.
DOI: 10.1038/gene.2014.82
Abstrakt: 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.
Databáze: MEDLINE