title: IFN-λ receptor 1 expression is induced in chronic hepatitis C and correlates with the IFN-λ3 genotype and with nonresponsiveness to IFN-α therapies.
abstract: The molecular mechanisms that link IFN-λ3 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-λ and of the specific IFN-λ receptor chain (IFN-λR1) in 122 liver biopsies of patients with CHC and 53 control samples. The IFN-λ3 genotype was not associated with differential expression of IFN-λ, but rather IFN-λR1. In a series of 30 primary human hepatocyte (PHH) samples, IFN-λR1 expression was low but could be induced with IFN-α. IFN-α-induced IFN-λR1 expression was significantly stronger in PHHs carrying the minor IFN-λ3 allele. The analysis of liver biopsies of patients with CHC revealed a strong association of high IFN-λR1 expression with elevated ISG expression, with IFN-λ3 minor alleles, and with nonresponse to pegylated IFN-α and ribavirin. The findings provide a missing link between the IFN-λ3 genotype and the associated phenotype of treatment nonresponse.
authors.affiliation: Department of Biomedicine; and 2 Division of Gastroenterology and Hepatology, University Hospital Basel; University of Basel, 4031 Basel, Switzerland.
authors.forename: Francois H T
authors.initials: FH
authors.lastname: Duong
authors.forename: Gaia
authors.initials: G
authors.lastname: Trincucci
authors.forename: Tujana
authors.initials: T
authors.lastname: Boldanova
authors.forename: Diego
authors.initials: D
authors.lastname: Calabrese
authors.forename: Benedetta
authors.initials: B
authors.lastname: Campana
authors.forename: Ilona
authors.initials: I
authors.lastname: Krol
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Durand
authors.forename: Laura
authors.initials: L
authors.lastname: Heydmann
authors.forename: Mirjam B
authors.initials: MB
authors.lastname: Zeisel
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
authors.forename: Markus H
authors.initials: MH
authors.lastname: Heim
mesh_terms: D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D018613:Microscopy, Confocal; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017471:Receptors, Interferon / Q000378:metabolism*; D013557:Switzerland
chemical_list: D017931:DNA Primers; D016898:Interferon-alpha; D017471:Receptors, Interferon; D007372:Interferons
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