PMID- 20077564
OWN - NLM
STAT- MEDLINE
DCOM- 20100421
LR  - 20211028
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 51
IP  - 4
DP  - 2010 Apr
TI  - Consistent beneficial effects of killer cell immunoglobulin-like receptor 2DL3 
      and group 1 human leukocyte antigen-C following exposure to hepatitis C virus.
PG  - 1168-75
LID - 10.1002/hep.23477 [doi]
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-Cw*03 was associated with 
      SVR (P = 0.004, OR = 3.4, 95% CI = 1.5-8.7) and KIR2DL3/KIR2DL3-HLA-Cw*03 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.
FAU - Knapp, Susanne
AU  - Knapp S
AD  - Department of Hepatology, Division of Medicine, Imperial College London, UK.
FAU - Warshow, Usama
AU  - Warshow U
FAU - Hegazy, Doha
AU  - Hegazy D
FAU - Brackenbury, Louise
AU  - Brackenbury L
FAU - Guha, I Neil
AU  - Guha IN
FAU - Fowell, Andrew
AU  - Fowell A
FAU - Little, Ann-Margaret
AU  - Little AM
FAU - Alexander, Graeme J
AU  - Alexander GJ
FAU - Rosenberg, William M C
AU  - Rosenberg WM
FAU - Cramp, Matthew E
AU  - Cramp ME
FAU - Khakoo, Salim I
AU  - Khakoo SI
LA  - eng
GR  - 076991/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (HLA-C Antigens)
RN  - 0 (KIR2DL3 protein, human)
RN  - 0 (Receptors, KIR2DL3)
SB  - IM
MH  - Adult
MH  - Female
MH  - HLA-C Antigens/genetics/*physiology
MH  - Hepatitis C/*immunology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Receptors, KIR2DL3/genetics/*physiology
PMC - PMC4202114
MID - EMS60551
OID - NLM: EMS60551
EDAT- 2010/01/16 06:00
MHDA- 2010/04/22 06:00
PMCR- 2014/10/20
CRDT- 2010/01/16 06:00
PHST- 2010/01/16 06:00 [entrez]
PHST- 2010/01/16 06:00 [pubmed]
PHST- 2010/04/22 06:00 [medline]
PHST- 2014/10/20 00:00 [pmc-release]
AID - 10.1002/hep.23477 [doi]
PST - ppublish
SO  - Hepatology. 2010 Apr;51(4):1168-75. doi: 10.1002/hep.23477.