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

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Duong, F | Trincucci, G | Boldanova, T | Calabrese, D | Campana, B | Krol, I | Durand, S | Heydmann, Laura | Zeisel, Mirjam | Baumert, Thomas | Heim, M

Edité par CCSD ; Rockefeller University Press -

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.

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