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.
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.
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DOI：
10.1084/jem.20131557
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发表时间：
2014-05-05
期刊：
影响因子：
--
通讯作者：
Heim MH
中科院分区：
文献类型：
--
作者：
Duong FH;Trincucci G;Boldanova T;Calabrese D;Campana B;Krol I;Durand SC;Heydmann L;Zeisel MB;Baumert TF;Heim MH
Liver biopsies from patients with chronic hepatitis C reveal high IFN-λR1 expression, which can be induced with IFN-α and is associated with elevated ISG expression, the IFN-λ3 minor alleles, and nonresponsiveness to peg-IFN-α and ribavirin therapy. 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.
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影响因子：
13.5
作者：
Ghany, Marc G.;Nelson, David R.;Strader, Doris B.;Thomas, David L.;Seeff, Leonard B.
通讯作者：
Seeff, Leonard B.
影响因子：
11.4
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Hartmann, Rune
影响因子：
29.4
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Duong, FHT;Filipowicz, M;Heim, MH
通讯作者：
Heim, MH
影响因子：
13.5
作者：
Krieger, Sophie E.;Zeisel, Mirjam B.;Baumert, Thomas F.
通讯作者：
Baumert, Thomas F.
影响因子：
3.7
作者：
François-Newton V;Magno de Freitas Almeida G;Payelle-Brogard B;Monneron D;Pichard-Garcia L;Piehler J;Pellegrini S;Uzé G
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Uzé G