PMID- 26381047
OWN - NLM
STAT- MEDLINE
DCOM- 20160614
LR  - 20231213
IS  - 1399-0039 (Electronic)
IS  - 0001-2815 (Print)
IS  - 0001-2815 (Linking)
VI  - 86
IP  - 4
DP  - 2015 Oct
TI  - The interaction of genetic determinants in the outcome of HCV infection: evidence 
      for discrete immunological pathways.
PG  - 267-75
LID - 10.1111/tan.12650 [doi]
AB  - 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)-lambda3/4, 
      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, chi(2) 
      test for trend, multivariate logistic regression, synergy and principal component 
      analysis (PCA). Although KIR2DL3:HLA-C1C1 (P = 0.027), IFN-lambda3/4 rs12979860 CC (P 
      = 0.027), tapasin G in individuals with aspartate at residue 114 of HLA-B 
      (TapG:HLA-B(114D) ) (P = 0.007) and HLA-DRB1*04:01 (P = 0.014) were associated 
      with SR with a strong additive influence (chi(2) test for trend P < 0.0001); 
      favorable polymorphisms did not interact synergistically, nor did patients 
      cluster by outcome. In the treatment cohort, IFN-lambda3/4 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.
CI  - (c) 2015 The Authors. Tissue Antigens published by John Wiley & Sons Ltd.
FAU - Hydes, T J
AU  - Hydes TJ
AD  - Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, 
      Southampton, UK.
FAU - Moesker, B
AU  - Moesker B
AD  - Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, 
      Southampton, UK.
FAU - Traherne, J A
AU  - Traherne JA
AD  - Department of Pathology, University of Cambridge, Cambridge, UK.
FAU - Ashraf, S
AU  - Ashraf S
AD  - Department of Pathology, University of Cambridge, Cambridge, UK.
FAU - Alexander, G J
AU  - Alexander GJ
AD  - Department of Medicine, University of Cambridge, Cambridge, UK.
FAU - Dimitrov, B D
AU  - Dimitrov BD
AD  - Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, 
      Southampton, UK.
AD  - Academic Unit of Primary Care and Population Sciences, Faculty of Medicine, 
      University of Southampton, Southampton, UK.
FAU - Woelk, C H
AU  - Woelk CH
AD  - Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, 
      Southampton, UK.
FAU - Trowsdale, J
AU  - Trowsdale J
AD  - Department of Pathology, University of Cambridge, Cambridge, UK.
FAU - Khakoo, S I
AU  - Khakoo SI
AD  - Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, 
      Southampton, UK.
LA  - eng
GR  - WT076991MA/WT_/Wellcome Trust/United Kingdom
GR  - G0901682/MRC_/Medical Research Council/United Kingdom
GR  - MR/M019829/1/MRC_/Medical Research Council/United Kingdom
GR  - MR/L016567/1/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 100140/WT_/Wellcome Trust/United Kingdom
GR  - G1001738/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (interferon-lambda, human)
RN  - 0 (IFNL4 protein, human)
RN  - 0 (Interleukins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Receptors, KIR)
RN  - 0 (tapasin)
RN  - 9008-11-1 (Interferons)
SB  - IM
MH  - Disease Progression
MH  - Epistasis, Genetic/*immunology
MH  - Gene Expression
MH  - Genetic Heterogeneity
MH  - Genotype
MH  - Hepacivirus/*immunology/pathogenicity
MH  - Hepatitis C, Chronic/diagnosis/*genetics/immunology/virology
MH  - Histocompatibility Antigens Class I/genetics/immunology
MH  - Histocompatibility Antigens Class II/genetics/immunology
MH  - Host-Pathogen Interactions/*genetics/immunology
MH  - Humans
MH  - Interferons
MH  - Interleukins/genetics/immunology
MH  - Liver Cirrhosis/diagnosis/*genetics/immunology/virology
MH  - Logistic Models
MH  - Membrane Transport Proteins/genetics/immunology
MH  - Multivariate Analysis
MH  - Prognosis
MH  - Receptors, KIR/genetics/immunology
MH  - Remission, Spontaneous
MH  - Retrospective Studies
PMC - PMC4858811
OTO - NOTNLM
OT  - IFN-lambda3/4
OT  - hepatitis C
OT  - immunogenetics
OT  - interferon
OT  - killer cell immunoglobulin receptors
OT  - tapasin
EDAT- 2015/09/19 06:00
MHDA- 2016/06/15 06:00
PMCR- 2016/05/06
CRDT- 2015/09/19 06:00
PHST- 2015/06/09 00:00 [received]
PHST- 2015/08/05 00:00 [revised]
PHST- 2015/08/10 00:00 [accepted]
PHST- 2015/09/19 06:00 [entrez]
PHST- 2015/09/19 06:00 [pubmed]
PHST- 2016/06/15 06:00 [medline]
PHST- 2016/05/06 00:00 [pmc-release]
AID - TAN12650 [pii]
AID - 10.1111/tan.12650 [doi]
PST - ppublish
SO  - Tissue Antigens. 2015 Oct;86(4):267-75. doi: 10.1111/tan.12650.