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

被引：59

作者：

Duong, Francois H. T. ^{[1
]}

Trincucci, Gaia ^{[1
]}

Boldanova, Tujana ^{[1
,2
]}

Calabrese, Diego ^{[1
]}

Campana, Benedetta ^{[1
,2
]}

Krol, Ilona ^{[1
]}

Durand, Sarah C. ^{[3
,4
]}

Heydmann, Laura ^{[3
,4
]}

Zeisel, Mirjam B. ^{[3
,4
]}

Baumert, Thomas F. ^{[3
,4
,5
]}

Heim, Markus H. ^{[1
]}

机构：

[1] Univ Basel, Dept Biomed, CH-4031 Basel, Switzerland

[2] Univ Basel, Univ Basel Hosp, Div Gastroenterol & Hepatol, CH-4031 Basel, Switzerland

[3] INSERM, U1110, F-67000 Strasbourg, France

[4] Univ Strasbourg, F-67081 Strasbourg, France

[5] Hop Univ Strasbourg, Pole Hepatodigestif, F-67091 Strasbourg, France

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2014年 / 211卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

GENOME-WIDE ASSOCIATION; INTERFERON-LAMBDA; VIRUS-INFECTION; GENETIC-VARIATION; SIGNAL-TRANSDUCTION; HUMAN HEPATOCYTES; STIMULATED GENES; IL28B; CLEARANCE; RIBAVIRIN;

D O I：

10.1084/jem.20131557

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

The molecular mechanisms that link IFN-lambda 3 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 receptor chain (IFN-lambda R1) in 122 liver biopsies of patients with CHC and 53 control samples. The IFN-lambda 3 genotype was not associated with differential expression of IFN-lambda, but rather IFN-lambda R1. In a series of 30 primary human hepatocyte (PHH) samples, IFN-lambda R1 expression was low but could be induced with IFN-alpha. IFN-alpha-induced IFN-lambda R1 expression was significantly stronger in PHHs carrying the minor IFN-lambda 3 allele. The analysis of liver biopsies of patients with CHC revealed a strong association of high IFN-lambda R1 expression with elevated ISG expression, with IFN-lambda 3 minor alleles, and with nonresponse to pegylated IFN-alpha and ribavirin. The findings provide a missing link between the IFN-lambda 3 genotype and the associated phenotype of treatment nonresponse.

引用

页码：857 / 868

页数：12

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