IFN-lambda receptor 1 expression is induced in chronic hepatitis C and correlates with the IFN-lambda3 genotype and with nonresponsiveness to IFN-alpha therapies.
Fiche publication
Date publication
mai 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas
Tous les auteurs :
Duong FH, Trincucci G, Boldanova T, Calabrese D, Campana B, Krol I, Durand SC, Heydmann L, Zeisel MB, Baumert TF, Heim MH
Lien Pubmed
Résumé
The molecular mechanisms that link IFN-lambda3 genotypes to differential induction of interferon (IFN)-stimulated genes (ISGs) in the liver of patients with chronic hepatitis C (CHC) are not known. We measured the expression of IFN-lambda and of the specific IFN-lambda receptor chain (IFN-lambdaR1) in 122 liver biopsies of patients with CHC and 53 control samples. The IFN-lambda3 genotype was not associated with differential expression of IFN-lambda, but rather IFN-lambdaR1. In a series of 30 primary human hepatocyte (PHH) samples, IFN-lambdaR1 expression was low but could be induced with IFN-alpha. IFN-alpha-induced IFN-lambdaR1 expression was significantly stronger in PHHs carrying the minor IFN-lambda3 allele. The analysis of liver biopsies of patients with CHC revealed a strong association of high IFN-lambdaR1 expression with elevated ISG expression, with IFN-lambda3 minor alleles, and with nonresponse to pegylated IFN-alpha and ribavirin. The findings provide a missing link between the IFN-lambda3 genotype and the associated phenotype of treatment nonresponse.
Référence
J Exp Med. 2014 May 5;211(5):857-68