Consistent beneficial effects of killer cell immunoglobulin‐like receptor 2DL3 and group 1 human leukocyte antigen‐C following exposure to hepatitis C virus

Knapp, S.; Warshow, Usama; Hegazy, Doha; Brackenbury, Louise S.; Guha, Indra Neil; Fowell, Andrew; Little, Ann‐Margaret; Alexander, Graeme; Rosenberg, William; Cramp, Matthew; Khakoo, Salim I.

doi:10.1002/hep.23477

Cited by 142 publications

(164 citation statements)

References 39 publications

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“…These include HLA‐I, HLA‐II, KIR, tapasin and IFN‐λ3/4 as described previously 9, 12, 14. Broadly speaking these represent a cellular innate immune response (IFN‐λ3/4), cytotoxic T‐lymphocytic response (HLA‐I and tapasin), T helper responses (HLA‐II) and NK cells (KIR), all of which have been implicated in the outcome of HCV infection.…”

Section: Resultsmentioning

confidence: 92%

“…The killer cell immunoglobulin (KIR) and human leukocyte antigen (HLA) combinations are also important for HCV outcomes in spontaneously resolving infection, IFN‐treatment‐associated resolution and in European‐exposed seronegative individuals 8, 14. In these studies, the combination of KIR2DL3 and its HLA‐C group 1 ligands (HLA‐C1) was protective in all groups tested in our UK population.…”

Section: Introductionmentioning

confidence: 85%

“…SR was defined as the absence of HCV RNA, 6 months following a positive antibody test. HCV genotyping was performed using quantitative polymerase chain reaction (PCR) (iQur, Southampton, UK) 9, 12, 14.…”

Section: Methodsmentioning

confidence: 99%

“…Genotyping had previously been performed for KIR, IFN‐λ3/4 rs12979860, HLA and tapasin 9, 12, 14. Additional high resolution KIR genotyping was later performed on the patients with chronic HCV infection to accurately determine KIR copy number and impute KIR haplotype 25.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2015

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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.

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Section: Resultsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

et al. 2015

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“…HLA-C molecules present ligands for KIR2DL receptors, with a functionally relevant dimorphism determining KIR specificity: for example, HLA-C group 1 (HLAC1) alleles, identified by Ser77/Asp80 of the HLA-C alpha 1 domain, are ligands for the inhibitory receptors KIR2DL2 and KIR2DL3 and the activating receptor KIR2DS2 [99,100]. KIR2DL3 and its ligand, HLA-C1, have been associated with an increased likelihood of spontaneous [101][102][103] and treatment-induced HCV clearance [102,103]. This association is attributed to differential natural killer (NK) cell activation and function in the context of this KIR/HLA interaction [104].…”

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

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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.

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The Immune Response to HCV in Acute and Chronic Infection

Thimme

Khakoo

2013

Viral Hepatitis

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Consistent beneficial effects of killer cell immunoglobulin‐like receptor 2DL3 and group 1 human leukocyte antigen‐C following exposure to hepatitis C virus

Abstract: Abbreviations: HCV, hepatitis C virus; HLA, human leukocyte antigen; IFN, interferon; KIR, MHC, major histocompatability complex; SVR, sustained virological response. From the

Cited by 142 publications

References 39 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

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

The Immune Response to HCV in Acute and Chronic Infection

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