Imperial College London
Professor Salim Khakoo

ProfessorSalimKhakoo

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 9024s.khakoo

 
 
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Location

 

HepatologySt Marys Multiple BuildingsSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Knapp:2010,
author = {Knapp, S and Warshow, U and Hegazy, D and Brackenbury, L and Guha, IN and Fowell, A and Little, AM and Alexander, GJ and WMC, R and Cramp, ME and Khakoo, SI},
journal = {Hepatology 2010 Apr 51(4)},
pages = {1168--1175},
title = {Consistent beneficial effects of killer cell immunoglobulin-like receptor 2DL3 and group 1 human leukocyte antigen-C following exposure to hepatitis C virus},
year = {2010}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Natural killer cells are a key component in the immune control of viral infections. Their functions are controlled by inhibitory receptors for major histocompatability complex (MHC) class I, including the killer cell immunoglobulin-like receptors (KIR). KIR2DL3 in combination with its cognate human leukocyte antigen (HLA)-C ligand has been shown to be associated with spontaneous resolution of viremia following hepatitis C virus (HCV) infection. In order to determine if this gene combination is advantageous across all potential outcomes following HCV exposure, we studied individuals with apparent resistance to HCV infection who remain seronegative and aviremic despite long-term injection drug use and also individuals chronically infected with HCV who successfully clear HCV with treatment. Homozygosity for KIR2DL3 in combination with group 1 HLA-C allotypes was more frequent in exposed seronegative aviremic individuals as compared to those with chronic HCV (25.0% versus 9.7%, P = 0.003, odds ratio [OR] = 3.1, 95% confidence interval [CI] = 1.3-7.1) in a model similar to that found for those spontaneously resolving HCV. In individuals undergoing treatment for HCV, those with KIR2DL3 and group 1 HLA-C were more likely to make a sustained virological response (SVR) (P = 0.013, OR = 2.3, 95% CI = 1.1-4.5). KIR and HLA-C protection in both treatment response and spontaneously resolving HCV was validated at the allelic level, in which KIR2DL3-HLA-Cw03 was associated with SVR (P = 0.004, OR = 3.4, 95% CI = 1.5-8.7) and KIR2DL3/KIR2DL3-HLA-Cw03 was associated with spontaneous resolution of HCV infection (P = 0.01, OR = 2.3, 95% CI = 1.2-4.4). Conclusion: KIR and HLA-C genes are consistently beneficial determinants in the outcome of HCV infection. This advantage extends to the allelic level for both gene families.
AU  - Knapp,S
AU  - Warshow,U
AU  - Hegazy,D
AU  - Brackenbury,L
AU  - Guha,IN
AU  - Fowell,A
AU  - Little,AM
AU  - Alexander,GJ
AU  - WMC,R
AU  - Cramp,ME
AU  - Khakoo,SI
EP  - 1175
PY  - 2010///
SP  - 1168
TI  - Consistent beneficial effects of killer cell immunoglobulin-like receptor 2DL3 and group 1 human leukocyte antigen-C following exposure to hepatitis C virus
T2  - Hepatology 2010 Apr 51(4)
ER  -
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