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interferon lambda

Robert Flisiak, Mitchell Shiffman, Juan Arenas, Hugo Cheinquer, Igor Nikitin, Yuping Dong, Khurram Rana, Subasree Srinivasan
BACKGROUND: A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection. METHODS: Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks...
2016: PloS One
Maryam Keshvari, Seyed Moayed Alavian, Bita Behnava, Ali Pouryasin, Johanna C Craig, Heidar Sharafi
BACKGROUND: The aim of this study was to determine whether two polymorphisms of the human interferon lambda 4 (IFNL4) gene (rs12979860 and rs8099917) can predict sustained virologic response (SVR) following antiviral therapy in patients with inherited bleeding disorder and chronic hepatitis C (CHC). METHODS: This retrospective study was conducted on 294 patients with congenital bleeding disorder and CHC who were treated with Peg-Interferon-α (PegIFN) and Ribavirin (RBV)...
October 13, 2016: Journal of Clinical Laboratory Analysis
Sujin Kim, Min-Ji Kim, Chang-Hoon Kim, Ju Wan Kang, Ha Kyung Shin, Dong-Young Kim, Tae-Bin Won, Doo Hee Han, Chae Seo Rhee, Joo-Heon Yoon, Hyun Jik Kim
RATIONALE AND OBJECTIVES: Here we studied the interferon (IFN)-regulated innate immune response against influenza A virus (IAV) infection in the mouse lung and the therapeutic effect of IFN-λ2/3 in acute IAV lung infection. . METHODS: For viral infections, IAV (WS/33, H1N1, PR8 H1N1, H5N1) were inoculated into WT mice by intranasal delivery and IAV mRNA level and viral titer were measured. To compare the antiviral effect of IFNs in vivo lung, neutralizing antibodies and recombinant IFNs were used...
September 15, 2016: American Journal of Respiratory Cell and Molecular Biology
Aoife Kelly, Mark W Robinson, Gerard Roche, Christine A Biron, Cliona O'Farrelly, Elizabeth J Ryan
The interferon lambda (IFN-λ) cytokines have well-known antiviral properties, yet their contribution to immune regulation is not well understood. Epithelial cells represent the major target cell of IFN-λ; peripheral blood mononuclear cells are generally considered nonresponsive, with the exception of plasmacytoid dendritic cells (pDCs). In this study we aimed to define the potential for discrete subpopulations of cells to directly respond to IFN-λ. Analysis of peripheral blood leukocytes reveals that, while pDCs uniformly express the highest levels of IFN-λ receptor, a small proportion of B cells and monocytes also express the receptor...
September 12, 2016: Journal of Interferon & Cytokine Research
Graham R Foster, Kazuaki Chayama, Wan-Long Chuang, Hugo Fainboim, Martti Farkkila, Adrian Gadano, Giovanni B Gaeta, Christophe Hézode, Yukiko Inada, Jeong Heo, Hiromitsu Kumada, Sheng-Nan Lu, Patrick Marcellin, Christophe Moreno, Stuart K Roberts, Simone I Strasser, Alexander J Thompson, Joji Toyota, Seung Woon Paik, John M Vierling, Anna L Zignego, David Cohen, Fiona McPhee, Megan Wind-Rotolo, Subasree Srinivasan, Matthew Hruska, Heather Myler, Simon D Portsmouth
BACKGROUND AND PURPOSE: Peginterferon Lambda was being developed as an alternative to alfa interferon for the treatment of chronic hepatitis C virus (HCV) infection. We compared peginterferon Lambda-1a plus ribavirin (Lambda/RBV) and Lambda/RBV plus daclatasvir (DCV; pangenotypic NS5A inhibitor) with peginterferon alfa-2a plus RBV (alfa/RBV) in treatment-naive patients with HCV genotype 2 or 3 infection. METHODS: In this multicenter, double-blind, phase 3 randomized controlled trial, patients were assigned 2:2:1 to receive 24 weeks of Lambda/RBV, 12 weeks of Lambda/RBV + DCV, or 24 weeks of alfa/RBV...
2016: SpringerPlus
Camila Fernanda da Silveira Alves, Camila Schultz Grott, Vagner Ricardo Lunge, Jorge Umberto Béria, Daniela Cardoso Tietzmann, Airton Tetelbom Stein, Daniel Simon
Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1) are co-infected with hepatitis C virus (HCV). Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815), which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism...
July 2016: Genetics and Molecular Biology
Camila Fernanda da Silveira Alves, Camila Schultz Grott, Vagner Ricardo Lunge, Jorge Umberto Béria, Daniela Cardoso Tietzmann, Airton Tetelbom Stein, Daniel Simon
Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1) are co-infected with hepatitis C virus (HCV). Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815), which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism...
July 25, 2016: Genetics and Molecular Biology
Yu-Lin Hsu, Mei-Yi Wang, Ling-Jun Ho, Jenn-Haung Lai
A marked increase in the rate of dengue virus (DENV) infection has resulted in more than 212 deaths in Taiwan since the beginning of 2015, mostly from fatal outcomes such as dengue hemorrhagic fever and dengue shock syndrome. The pathogenic mechanisms of these fatal manifestations are poorly understood. Cytokines induce an overwhelming immune reaction and thus have crucial roles. Interferon-lambda (IFN-λ), a newly identified IFN subtype, has antiviral effects, but its immunologic effects in DENV infection have not been investigated...
2016: Scientific Reports
Ahmed Lasfar, Helen Gogas, Andrew Zloza, Howard L Kaufman, John M Kirkwood
Interferon-lambda (IFN-λ) is a new IFN type, related to IFN-α, that is commonly used in the clinic. However, significant side effects accompanying IFN-α treatment limit enthusiasm for IFN-α. In this review, we discuss the current landscape of IFN-α use in oncology and describe the biologic characteristics of IFN-λ. IFN-λ offers unique advantages, including a more tumor cell selective targeting, lower off-target binding and an ability to generate both innate and adaptive immune responses. IFN-λ has also demonstrated therapeutic benefit in murine cancer models...
July 2016: Immunotherapy
Zaigham Abbas, Javed Yakoob, Muhammad A Umer, Ali A Azeem, Saeed S Hamid, Wasim Jafri
OBJECTIVE: To assess the role of single nucleotide polymorphisms (SNPs) near the interferon lambda-3 (IFNλ3) (formal IL-28B) gene rs12979860 in predicting sustained virologic response (SVR) in hepatitis-C virus genotype-3 (HCV-3). STUDY DESIGN: Descriptive, analytical study. PLACE AND DURATION OF STUDY: Department of Medicine, The Aga Khan University Hospital, Karachi, from July 2012 to June 2014. METHODOLOGY: Patients with HCV-3 were classified as sustained virologic response (SVR), relapsers and non-responders...
June 2016: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
E Santagostino, S Pol, A Olveira, H W Reesink, K van Erpecum, P Bogomolov, D Xu, L Critelli, S Srinivasan, E Cooney
AIM: This study explores the potential role of a novel interferon-containing regimen for treatment of patients with chronic hepatitis C (CHC) and underlying haemophilia. METHODS: This trial (NCT01741545) was an open-label, non-randomized phase 3 study, which included adult haemophiliacs with hepatitis C virus (HCV). Patients with HCV genotypes (GT)-2 or -3 were treated with Lambda-IFN/ribavirin (RBV)/daclatasvir (DCV) for 12 weeks (cohort A). Patients with HCV GT-1b or -4 were treated with Lambda-IFN/RBV/DCV for 12 weeks, followed by Lambda-IFN/RBV for an additional 12 weeks (cohort B)...
September 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
K S O'Connor, S A Read, M Wang, S Schibeci, M Eslam, A Ong, M D Weltman, M W Douglas, A Mazzola, A Craxì, S Petta, G J Stewart, C Liddle, J George, G Ahlenstiel, D R Booth
Single-nucleotide polymorphisms near the interferon lambda 3 (IFNL3) gene predict outcomes to infection and anti-viral treatment in hepatitis C virus (HCV) infection. To identify IFNL3 genotype effects on peripheral blood, we collected phenotype data on 400 patients with genotype 1 chronic hepatitis C (CHC). The IFNL3 responder genotype predicted significantly lower white blood cells (WBCs), as well as lower absolute numbers of monocytes, neutrophils and lymphocytes for both rs8099917 and rs12979860. We sought to define the WBC subsets driving this association using flow cytometry of 67 untreated CHC individuals...
September 2016: Genes and Immunity
Weiguo Fan, Shiqi Xie, Xinhao Zhao, Nan Li, Chong Chang, Li Li, Ge Yu, Xiumei Chi, Yu Pan, Junqi Niu, Jin Zhong, Bing Sun
The recently discovered interferon lambda 4 (IFN-λ4) is a new member of the human type III interferons which could induce a strong antiviral effect through the JAK-STAT cascade. However, hepatitis C virus (HCV) patients who are capable of expressing IFN-λ4 usually have poor response to IFN-α treatment, and the mechanism behind this paradox remains unknown. Here, we reported that IFN-λ4 desensitized IFN-α-stimulated JAK-STAT signalling. Microarray analysis revealed that IFN-λ4 could induce ubiquitin specific peptidase 18 (USP18), a known inhibitor of the type I IFN signalling pathway, in a more sustained pattern compared with type I interferon induction...
September 2016: Journal of General Virology
S Chinnaswamy
Interferon (IFN) lambda (IFN-λ or type III IFN) gene polymorphisms were discovered in the year 2009 to have a strong association with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection in human hosts. This landmark discovery also brought renewed interest in type III IFN biology. After more than half a decade since this discovery, we now have reports that show that genetic association of IFNL gene polymorphisms in humans is not limited only to HCV infections but extends beyond, to include varied diseases such as non-alcoholic fatty liver disease, allergy and several other viral diseases including that caused by the human immunodeficiency virus...
July 2016: Genes and Immunity
Zahra Heidari, Bita Moudi, Hamidreza Mahmoudzadeh-Sagheb, Mohammad Hashemi
BACKGROUND: Cytokines are proteins that mediate innate and adaptive immunity responses. It is hypothesized that interferon lambda 3 (IFNL3) levels can influence the outcome of chronic hepatitis B virus (HBV) infection. Polymorphisms in IFN genes have been associated with response to infection. OBJECTIVES: This study was carried-out to investigate the association of IFNL3 gene polymorphisms (rs12979860 and rs8099917) with HBV susceptibility, in chronic HBV-infected patients...
March 2016: Hepatitis Monthly
David A Sheridan, Behzad Hajarizadeh, Fiona I Fenwick, Gail V Matthews, Tanya Applegate, Mark Douglas, Dermot Neely, Bev Askew, Gregory J Dore, Andrew R Lloyd, Jacob George, Margaret F Bassendine, Jason Grebely
BACKGROUND & AIMS: Hepatitis C virus (HCV) is bound to plasma lipoproteins and circulates as an infectious lipoviral particle (LVP). Experimental evidence indicates that LVPs have decreased susceptibility to antibody mediated neutralisation and higher infectivity. This study tested the hypothesis that LVPs are required to establish persistent infection, and conversely, low levels of LVP in recent HCV infection increase the probability of spontaneous HCV clearance. METHODS: LVP in non-fasting plasma was measured using the concentration of HCV RNA bound to large >100 nM sized lipoproteins after ex vivo addition of a lipid emulsion, that represented the maximum concentration of LVP (maxi-LVP)...
May 25, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Janett Fischer, Alexander N R Weber, Stephan Böhm, Sabine Dickhöfer, Souhayla El Maadidi, Danilo Deichsel, Viola Knop, Hartwig Klinker, Bernd Möller, Jens Rasenack, Lisa Wang, Manu Sharma, Holger Hinrichsen, Ulrich Spengler, Peter Buggisch, Christoph Sarrazin, Michael Pawlita, Tim Waterboer, Manfred Wiese, Elsbeth Probst-Müller, Raffaele Malinverni, Pierre-Yves Bochud, Clair Gardiner, Cliona O'Farrelly, Thomas Berg
OBJECTIVE: As pathogen sensors, Toll-like receptors (TLR) play a role in the first defence line during HCV infection. However, the impact of the DNA sensor TLR9 on the natural course of HCV infection is unknown. To address this, TLR9 promoter polymorphisms (single nucleotide polymorphisms (SNPs)) rs187084 and rs5743836 were investigated for their effect on disease progression. DESIGN: Therefore, the TLR9 SNPs and the interferon lambda 4 (IFNL4) rs12979860 were genotyped in chronically HCV type 1 infected (n=333), in patients who spontaneously cleared the infection (n=161), in the Swiss HCV cohort (n=1057) and the well-characterised German (n=305) and Irish (n=198) 'anti-D' cohorts...
April 21, 2016: Gut
Anna Wróblewska, Agnieszka Bernat, Anna Woziwodzka, Joanna Markiewicz, Tomasz Romanowski, Krzysztof P Bielawski, Tomasz Smiatacz, Katarzyna Sikorska
Single nucleotide polymorphisms (SNPs) within DNA region containing interferon lambda 3 (IFNL3) and IFNL4 genes are prognostic factors of treatment response in chronic hepatitis C (CHC). Iron overload, frequently diagnosed in CHC, is associated with unfavorable disease course and a risk of carcinogenesis. Its etiology and relationship with the immune response in CHC are not fully explained. Our aim was to determine whether IFNL polymorphisms in CHC patients associate with body iron indices, and whether they are linked with hepatic expression of genes involved in iron homeostasis and IFN signaling...
April 28, 2016: Clinical and Experimental Medicine
Maho Suzukawa, Shunsuke Akashi, Hideaki Nagai, Hiroyuki Nagase, Hiroyuki Nakamura, Hirotoshi Matsui, Akira Hebisawa, Ken Ohta
The QuantiFERON®-TB Gold In-Tube test (QFT), an interferon-γ release assay, is used to diagnose Mycobacterium tuberculosis, but its inaccuracy in distinguishing active tuberculosis from latent infection is a major concern. There is thus a need for an easy and accurate tool for achieving that goal in daily clinical settings. This study aimed to identify candidate cytokines for specifically differentiating active tuberculosis from latent infection. Our study population consisted of 31 active TB (tuberculosis) patients, 29 LTBI (latent tuberculosis infection) patients and 10 healthy control subjects...
2016: PloS One
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