PMID- 23532923
OWN - NLM
STAT- MEDLINE
DCOM- 20140213
LR  - 20211021
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 58
IP  - 3
DP  - 2013 Sep
TI  - Synergism of tapasin and human leukocyte antigens in resolving hepatitis C virus 
      infection.
PG  - 881-9
LID - 10.1002/hep.26415 [doi]
AB  - CD8+ T-cell responses to hepatitis C virus (HCV) are important in generating a 
      successful immune response and spontaneously clearing infection. Human leukocyte 
      antigen (HLA) class I presents viral peptides to CD8+ T cells to permit detection 
      of infected cells, and tapasin is an important component of the peptide loading 
      complex for HLA class I. We sought to determine if tapasin polymorphisms affected 
      the outcome of HCV infection. Patients with resolved or chronic HCV infection 
      were genotyped for the known G/C coding polymorphism in exon 4 of the tapasin 
      gene. In a European, but not a US, Caucasian population, the tapasin G allele was 
      significantly associated with the outcome of HCV infection, being found in 82.5% 
      of resolvers versus 71.3% of persistently infected individuals (P = 0.02, odds 
      ratio [OR] = 1.90 95% confidence interval [CI] = 1.11-3.23). This was more marked 
      at the HLA-B locus at which heterozygosity of both tapasin and HLA-B was 
      protective (P < 0.03). Individuals with an HLA-B allele with an aspartate at 
      residue 114 and the tapasin G allele were more likely to spontaneously resolve 
      HCV infection (P < 0.00003, OR = 3.2 95% CI = 1.6-6.6). Additionally, individuals 
      with chronic HCV and the combination of an HLA-B allele with an aspartate at 
      residue 114 and the tapasin G allele also had stronger CD8+ T-cell responses 
      (P = 0.02, OR = 2.58, 95% CI-1.05-6.5). CONCLUSION: Tapasin alleles contribute to 
      the outcome of HCV infection by synergizing with polymorphisms at HLA-B in a 
      population-specific manner. This polymorphism may be relevant for peptide 
      vaccination strategies against HCV infection.
CI  - (c) 2013 by the American Association for the Study of Liver Diseases.
FAU - Ashraf, Shirin
AU  - Ashraf S
AD  - Clinical and Experimental Sciences, Faculty of Medicine, University of 
      Southampton, UK.
FAU - Nitschke, Katja
AU  - Nitschke K
FAU - Warshow, Usama M
AU  - Warshow UM
FAU - Brooks, Collin R
AU  - Brooks CR
FAU - Kim, Arthur Y
AU  - Kim AY
FAU - Lauer, Georg M
AU  - Lauer GM
FAU - Hydes, Theresa J
AU  - Hydes TJ
FAU - Cramp, Matthew E
AU  - Cramp ME
FAU - Alexander, Graeme
AU  - Alexander G
FAU - Little, Ann-Margaret
AU  - Little AM
FAU - Thimme, Robert
AU  - Thimme R
FAU - Neumann-Haefelin, Christoph
AU  - Neumann-Haefelin C
FAU - Khakoo, Salim I
AU  - Khakoo SI
LA  - eng
GR  - R01 DA033541/DA/NIDA NIH HHS/United States
GR  - U19 AI0663445/AI/NIAID NIH HHS/United States
GR  - U19 AI082630/AI/NIAID NIH HHS/United States
GR  - U19 AI066345/AI/NIAID NIH HHS/United States
GR  - G1001738/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130729
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Antiviral Agents)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (tapasin)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Antiviral Agents/therapeutic use
MH  - Cohort Studies
MH  - Female
MH  - HLA Antigens/genetics/*physiology
MH  - HLA-B Antigens/genetics/physiology
MH  - *Hepacivirus
MH  - Hepatitis C/*drug therapy/*physiopathology
MH  - Humans
MH  - Logistic Models
MH  - Male
MH  - Membrane Transport Proteins/genetics/*physiology
MH  - Middle Aged
MH  - Polymorphism, Genetic/genetics
MH  - Prognosis
MH  - Treatment Outcome
PMC - PMC3759612
MID - NIHMS460774
EDAT- 2013/03/28 06:00
MHDA- 2014/02/14 06:00
PMCR- 2014/09/01
CRDT- 2013/03/28 06:00
PHST- 2012/08/30 00:00 [received]
PHST- 2013/03/21 00:00 [accepted]
PHST- 2013/03/28 06:00 [entrez]
PHST- 2013/03/28 06:00 [pubmed]
PHST- 2014/02/14 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - 10.1002/hep.26415 [doi]
PST - ppublish
SO  - Hepatology. 2013 Sep;58(3):881-9. doi: 10.1002/hep.26415. Epub 2013 Jul 29.