Introduction to the genetics and biology of interleukin-28B

Charlton, Michael; Goldstein, David B.

doi:10.1002/hep.25794

Cited by 22 publications

(22 citation statements)

References 52 publications

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“…Three interferon (IFN)-λ genes, IFNL1 , IFNL2 (formerly IL29 and IL28A , respectively) and IFNL3 reside downstream of the rs12979860 SNP [3]. IFN-λ genes encode the type III IFNs.…”

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of rs12979860 SNP of the IFNL3 Gene in Children with Hepatitis C and Ethnic Matched Controls Using 1000 Genomes Project Data

et al. 2014

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The rs12979860 single nucleotide polymorphism located on chromosome 19q13.13 near the interferon L3 gene (formerly and commonly known as interleukin 28B gene) has been associated in adults with both spontaneous and treatment induced clearance of hepatitis C virus. Although the exact mechanism of these associations remains unclear, it suggests that variation in genes involved in the immune response against the virus favours viral clearance. Limited and preliminary data are available on this issue in children. The aim of the present study was to evaluate, in a representative cohort of children with perinatal infection, the potential association between rs12979860 single nucleotide polymorphism and the outcome of hepatitis C virus infection. Alleles and genotypes frequencies were evaluated in 30 children who spontaneously cleared the virus and in 147 children with persistent infection and were compared with a population sample of ethnically matched controls with unknown hepatitis C status obtained using the 1000 Genomes Project data. The C allele and the C/C genotype showed greater frequencies in the clearance group (76.7% and 56.7%, respectively) when compared with both children with viral persistence (C allele 56.5%, p = 0.004; C/C genotype 32.7%, p = 0.02) and with the ethnically matched individuals (C allele 59.7%, p = 0.02; C/C genotype 34.7%, p = 0.03). Children with the C/C genotype were 2 times more likely to clear hepatitis C virus relative to children with the C/T and T/T genotypes combined (odds ratio: 2.7; 90% confidence intervals: 1.3–5.8). The present study provides the evidence that the rs12979860 single nucleotide polymorphism influences the natural history of hepatitis C virus in children.

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“…Three interferon (IFN)-λ genes, IFNL1 , IFNL2 (formerly IL29 and IL28A , respectively) and IFNL3 reside downstream of the rs12979860 SNP [3]. IFN-λ genes encode the type III IFNs.…”

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of rs12979860 SNP of the IFNL3 Gene in Children with Hepatitis C and Ethnic Matched Controls Using 1000 Genomes Project Data

et al. 2014

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“…Our results suggest that agents providing viral suppression leading to RVR and EVR including n-IFN-beta, DAAs and newly developed agents are preferable for the initial early induction therapy. IFNs show the first line of defense against viruses and act directly on viral replication and indirectly via the activation of immune responses [10]. IFN-beta was previously shown to have different signaling and biological activities from those of IFN-alpha, and achieved a higher rate of viral clearance than IFN-alpha [18][19][20][21][22][23].…”

Section: Discussionmentioning

confidence: 99%

“…The nonstructural proteins of HCV, particularly NS3-4A, have been found to interfere with type I IFN induction pathways. IFNs show the first line of defense against viruses and act directly on viral replication and indirectly via the activation of immune responses [10]. The HCV clearance may lead to restoration of innate and adaptive immune responses [11][12][13].…”

Section: Case Reportmentioning

confidence: 99%

Treatment of Chronic Hepatitis C with Viral-Suppression linked to Restoration of Innate-Immune Responses with Induction-Therapy with n-IFN-beta followed by Simeprevir

Kishida¹

2015

MOJI

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Complications associated with hepatitis C virus (HCV) infection may be prevented by viral eradication. Response rates with direct-acting antivirals regimens are generally lower in chronic hepatitis C (CHC) patients who have failed to respond to previous interferon (IFN) treatments. HCV persistence in the host results from in efficient innate and adaptive immune responses. The resolution of a HCV infection may restore impairments in innate and adaptive immunities. Our previous study suggested that induction treatment with natural (n)-IFN-beta followed by maintenance treatment with n-IFN-alpha restored innate immune responses, as indicated by the significant increase of IL-12, and IL-15 and significant decrease of CXCL-8. Persistent virologic clearance and the restoration of innate immune responses with Simeprevir plus Pegylated (Peg) -IFN-alpha/ribavirin (RBV) were more likely to result in a sustained virologic response (SVR). On the basis of these findings, we conducted to treat a CHC patient with genotype 1b, a high viral load, a prior null response to IFN treatments and chronic active hepatitis with advanced fibrosis using induction therapy with n-IFN-beta followed by Simeprevir plus Peg-IFN-alpha-2b/RBV. This is the first case of difficult-to-treat CHC with genotype 1b, a high viral load, null response to previous IFN treatment and advanced hepatic fibrosis that was successfully treated with induction therapy using n-IFN-beta, which induced the viral clearance of serum HCV RNA, followed by Simeprevir plus Peg-IFN-alpha-2b/RBV. Persistent viral clearance linked to restoration of innate immune responses and SVR were achieved 12 weeks after cessation of the treatment without virologic breakthrough or relapse and sustained biochemical response. Anemia and thrombocytopenia were managed without discontinuation of the treatment. Induction therapy with n-IFN-beta followed by Simeprevir plus Peg-IFN-alpha-2b/RBV was tolerated well and only mild adverse effects were noted. It also effectively eradicated HCV infection in a difficult-to-treat CHC patient with advanced fibrosis.

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“…Sequencing reactions were performed with the BigDye Terminator Cycle Sequencing kit and submitted on an ABI Prism 3100 Genetic Analyser (Applied Biosystems, CA, USA). The rs12979860 was genotyped using the ABI TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA, USA) [15]. …”

Section: Methodsmentioning

confidence: 99%

A Fast and Cost-Effective Method for Identifying a Polymorphism of Interleukin 28B Related to Hepatitis C

et al. 2013

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Approximately 170 million people are chronic carriers of hepatitis C virus (HCV). Patients with chronic hepatitis C are currently treated with pegylated interferon and ribavirin (PEG-IFN/RBV). A genome-wide association with PEG-IFN/RBV treatment response and a single nucleotide polymorphism (rs12979860) has been identified near the interleukin 28B gene that encodes interferon-λ-3. In this paper, we describe an innovative, fast, and low-cost multiplex polymerase chain reaction with confronting two-pair primers that detects the rs12979860 polymorphism. The assay is internally controlled and does not require the use of restriction endonucleases or special equipment. Moreover, the assay decreases costs, being about 40% cheaper than direct sequencing methods.

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Introduction to the genetics and biology of interleukin-28B

Cited by 22 publications

References 52 publications

Comparative Analysis of rs12979860 SNP of the IFNL3 Gene in Children with Hepatitis C and Ethnic Matched Controls Using 1000 Genomes Project Data

Comparative Analysis of rs12979860 SNP of the IFNL3 Gene in Children with Hepatitis C and Ethnic Matched Controls Using 1000 Genomes Project Data

Treatment of Chronic Hepatitis C with Viral-Suppression linked to Restoration of Innate-Immune Responses with Induction-Therapy with n-IFN-beta followed by Simeprevir

A Fast and Cost-Effective Method for Identifying a Polymorphism of Interleukin 28B Related to Hepatitis C

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