ArticleJournal of gastroenterology2014
Ex vivo induction of IFN-λ3 by a TLR7 agonist determines response to Peg-IFN/ribavirin therapy in chronic hepatitis C patients.
Article in Journal of gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Functional genetic variants of the IFN-λ3 (IL28B) gene and transcription factor interactions on its promoter.Cytokine · 2021Article
- IFN-λ3, not IFN-λ4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis.Nature genetics · 2017Article
- Interferon-λs and Plasmacytoid Dendritic Cells: A Close Relationship.Frontiers in immunology · 2017Review
- Immunopathogenesis of Hepatitis C Virus Infection.Gastroenterology clinics of North America · 2015Review
- IFNL3 mRNA structure is remodeled by a functional non-coding polymorphism associated with hepatitis C virus clearance.Scientific reports · 2015Article
- Is the use of IL28B genotype justified in the era of interferon-free treatments for hepatitis C?World journal of virology · 2015Article
- Vitamin D and chronic hepatitis C: effects on success rate and prevention of side effects associated with pegylated interferon-α and ribavirin.International journal of clinical and experimental medicine · 2015Review
- Activins and Follistatin in Chronic Hepatitis C and Its Treatment with Pegylated-Interferon-α Based Therapy.Mediators of inflammation · 2015Review
- Dendritic cells in hepatitis C virus infection: key players in the IFNL3-genotype response.World journal of gastroenterology · 2014Review
- Genetic variants at the IFNL3 locus and their association with hepatitis C virus infections reveal novel insights into host-virus interactions.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2014Review
- Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenetic variation around interleukin-28B (IL28B), encoding IFN-λ3, predict non-responders to pegylated interferon-α/ribavirin (Peg-IFN/RBV) therapy in chronic hepatitis C (CHC). However, it remains unclear the expression and the role of IL28B itself. The aim of this study is to develop easy and useful methods for the prediction of treatment outcomes.
methodsThe mRNA and protein levels of IFN-λ3 induced by ex vivo stimulation of peripheral blood mononuclear cells (PBMC) or magnetically selected dendritic cells (DCs) with toll-like receptor agonists (TLR3; poly I:C, TLR7; R-837) were measured by the quantitative real-time polymerase chain reaction and our newly developed chemiluminescence enzyme immunoassays, respectively, and compared with the clinical data.
resultsWe found that BDCA-4(+) plasmacytoid and BDCA-3(+) myeloid DCs were the main producers of IFN-λs when stimulated with R-837 and poly I:C, respectively. Detectable levels of IFN-λs were inducible even in a small amount of PBMC, and IFN-λ3 was more robustly up-regulated by R-837 in PBMC of CHC patients with favorable genotype for the response to Peg-IFN/RBV (TT in rs8099917) than those with TG/GG. Importantly, the protein levels of IFN-λ3 induced by R-837 clearly differentiated the response to Peg-IFN/RBV treatment (p = 1.0 × 10(-10)), including cases that IL28B genotyping failed to predict the treatment response. The measurement of IFN-λ3 protein more accurately predicted treatment efficacies (95.7 %) than that of IL28B genotyping (65.2 %).
conclusionsGenetic variations around IL28B basically affect IFN-λ3 production, but different amounts of IFN-λ3 protein determines the outcomes of Peg-IFN/RBV treatment. This study, for the first time, presents compelling evidence that IL28B confer a functional phenotype.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.