IL28B, HLA-C, and KIR Variants Additively Predict Response to Therapy in Chronic Hepatitis C Virus Infection in a European Cohort: A Cross-Sectional Study

Suppiah, Vijayaprakash; Gaudieri, Silvana; Armstrong, Nicola J.; O'Connor, K.; Berg, Thomas; Weltman, Martin; Abate, Maria Lorena; Spengler, Ulrich; Bassendine, Margaret F.; Dore, Gregory J.; Irving, William L.; Powell, Elizabeth E.; Hellard, Margaret; Riordan, Stephen M.; Matthews, Gail V.; Sheridan, David; Nattermann, Jacob; Smedile, Antonina; Müller, Tobias; Hammond, E.; Dunn, David S.; Negro, Francesco; Bochud, Pierre–Yves; Mallal, S.; Ahlenstiel, Golo; Stewart, Graeme J.; George, Jacob; Booth, David R.

doi:10.1371/journal.pmed.1001092

Cited by 111 publications

(90 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, susceptibility factors appear to increase susceptibility. This was found in an Irish cohort, but not a larger international study 20, 21. Similarly, considering viral genotype and the response to IFN‐based therapy, IFN‐λ3/4 and centromeric A KIR haplotypes are important for treatment‐induced resolution of patients infected with HCV G1, whereas the KIR2DL3 and HLA‐class I combination, but not IFN‐λ3/4, plays a dominant role in resolving HCV G2 and G3 infection.…”

Section: Discussionmentioning

confidence: 83%

“…In these studies it has been shown that for the SNPs associated with worse outcomes, KIR2DS3, HLA‐C2C2 and IFN‐λ3/4 (rs8099917 G allele and rs12979860 T allele), there appeared to be an interaction, as individuals with two susceptibility factors had significantly worse outcomes than those with only one 20, 21. Conversely no predictive benefit was found on combining the favorable IFN‐λ3/4 polymorphism with KIR2DL3:HLA‐C1 homozygosity for protection against viremia in seronegative exposed groups 12.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The interaction of genetic determinants in the outcome of HCV infection: evidence for discrete immunological pathways

et al. 2015

View full text Add to dashboard Cite

Diversity within the innate and adaptive immune response to hepatitis C is important in determining spontaneous resolution (SR) and treatment response. The aim of this study was to analyze how these variables interact in combination; furthering our understanding of the mechanisms that drive successful immunological clearance. Multivariate analysis was performed on retrospectively collected data for 357 patients previously genotyped for interferon (IFN)‐λ3/4, killer cell immunoglobulin (KIR), human leukocyte antigen (HLA) class I and II and tapasin. High resolution KIR genotyping was performed for individuals with chronic infection and haplotypes determined. Outcomes for SR, IFN response and cirrhosis were examined. Statistical analysis included univariate methods, χ2 test for trend, multivariate logistic regression, synergy and principal component analysis (PCA). Although KIR2DL3:HLA‐C1C1 (P = 0.027), IFN‐λ3/4 rs12979860 CC (P = 0.027), tapasin G in individuals with aspartate at residue 114 of HLA‐B (TapG:HLA‐B114D) (P = 0.007) and HLA‐DRB1*04:01 (P = 0.014) were associated with SR with a strong additive influence (χ2 test for trend P < 0.0001); favorable polymorphisms did not interact synergistically, nor did patients cluster by outcome. In the treatment cohort, IFN‐λ3/4 rs12979860 CC was protective in hepatitis C virus (HCV) G1 infection and KIR2DL3:HLA‐C1 in HCV G2/3. In common with SR, variables did not interact synergistically. Polymorphisms predictive of viral clearance did not predict disease progression. In summary, different individuals resolve HCV infection using discrete and non‐interacting immunological pathways. These pathways are influenced by viral genotype. This work provides novel insights into the complexity of the interaction between host and viral factors in determining the outcome of HCV infection.

show abstract

Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

The interaction of genetic determinants in the outcome of HCV infection: evidence for discrete immunological pathways

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In a later Irish study, the authors found that CCR5-∆32 was significantly associated with increased spontaneous CCR5-∆32 and IL28B polymorphisms in treatment of HCV infection 14 . Importantly, this effect seemed to be due to an interaction of CCR5-∆32 with the recently described IL28B rs12979860 polymorphism, which has also been shown to influence spontaneous recovery from HCV infection 15,16 . As IL28B polymorphisms are currently the strongest host genetic markers to predict treatmentinduced clearance of HCV infection [17][18][19][20] , we designed this study to examine for a possible interaction between the CCR5-∆32 mutation and the two most predictive IL28B polymorphisms, rs8099917 and rs12979860, with respect to treatment-induced clearance of HCV infection.…”

Section: Introductionmentioning

confidence: 93%

“…Written informed consent was obtained from all participants. Characteristics of the study cohorts have been described elsewhere 16 . Briefly, all treated patients were Caucasian and infected with genotype 1, the majority of these patients received pegylated interferon and ribavirin and had virological response determined 6 months after completion of therapy.…”

Section: Ethical Approval Was Obtained From the Human Research Ethicsmentioning

confidence: 99%

CCR5-Δ32 genotype does not improve predictive value of IL28B polymorphisms for treatment response in chronic HCV infection

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…This association is attributed to differential natural killer (NK) cell activation and function in the context of this KIR/HLA interaction [104]. In a recent cross-sectional study, Suppiah et al concluded that IL28-B, HLA-C, and KIR variants additively predict response to therapy in CHC European patients [105].…”

Section: Molecular Epidemiology Of Hcv-relatedmentioning

confidence: 99%

Evolving Trends in the Hepatitis C Virus Molecular Epidemiology Studies: From the Viral Sequences to the Human Genome

Trinks

Gadano

Argibay

2012

Epidemiology Research International

View full text Add to dashboard Cite

Hepatitis C virus (HCV) represents a major worldwide public health problem. The search for the key molecular biomarkers that may provide insight on the basis of the differences in disease progression, severity, and response to therapy is crucial for understanding the natural history of HCV, for estimating the burden of infection and for developing preventive interventions. Initially, molecular epidemiology studies have focused on studying the viral genetic diversity (genotypes, genetic variants, specific nucleotide and amino acid substitutions). However, the clinical heterogeneities of HCV infection and the imperfect predictability of the response to treatment have suggested the need to search for host genetic biomarkers. This led to the discovery of genetic polymorphisms playing a major role in the evolution of infection, as well as in treatment response and adverse effects, such asIL-28B,ITPA, andIP-10. As a consequence, nowadays the focus of molecular epidemiology studies has turned from the viral to the human genome. This paper will cover recent reports on the subject describing the most relevant viral as well as host genetic risk factors analyzed by past and current HCV molecular epidemiology studies.

show abstract

IL28B, HLA-C, and KIR Variants Additively Predict Response to Therapy in Chronic Hepatitis C Virus Infection in a European Cohort: A Cross-Sectional Study

Abstract: Vijayaprakash Suppiah and colleagues show that genotyping hepatitis C patients for the IL28B, HLA-C, and KIR genes improves the ability to predict whether or not patients will respond to antiviral treatment.

Cited by 111 publications

References 35 publications

The interaction of genetic determinants in the outcome of HCV infection: evidence for discrete immunological pathways

The interaction of genetic determinants in the outcome of HCV infection: evidence for discrete immunological pathways

CCR5-Δ32 genotype does not improve predictive value of IL28B polymorphisms for treatment response in chronic HCV infection

Evolving Trends in the Hepatitis C Virus Molecular Epidemiology Studies: From the Viral Sequences to the Human Genome

Contact Info

Product

Resources

About