Duong, Francois H. T. and Trincucci, Gaia and Boldanova, Tujana and Calabrese, Diego and Campana, Benedetta and Krol, Ilona and Durand, Sarah C. and Heydmann, Laura and Zeisel, Mirjam B. and Baumert, Thomas F. and Heim, Markus H.. (2014) 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. Journal of Experimental Medicine, 211 (5). pp. 857-868.
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Official URL: https://edoc.unibas.ch/61772/
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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.
Faculties and Departments: | 03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Hepatology Laboratory (Heim) |
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UniBasel Contributors: | Calabrese, Diego and Heim, Markus H. |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | Rockefeller University Press |
ISSN: | 0022-1007 |
e-ISSN: | 1540-9538 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
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Identification Number: |
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Last Modified: | 23 Jul 2020 12:12 |
Deposited On: | 23 Jul 2020 12:12 |
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