Document Detail

Synergism of tapasin and human leukocyte antigens in resolving hepatitis C virus infection.
MedLine Citation:
PMID:  23532923     Owner:  NLM     Status:  MEDLINE    
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.
Shirin Ashraf; Katja Nitschke; Usama M Warshow; Collin R Brooks; Arthur Y Kim; Georg M Lauer; Theresa J Hydes; Matthew E Cramp; Graeme Alexander; Ann-Margaret Little; Robert Thimme; Christoph Neumann-Haefelin; Salim I Khakoo
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Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-07-29
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  58     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-09-02     Completed Date:  2014-02-13     Revised Date:  2014-07-04    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  881-9     Citation Subset:  IM    
Copyright Information:
© 2013 by the American Association for the Study of Liver Diseases.
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MeSH Terms
Antiviral Agents / therapeutic use
Cohort Studies
HLA Antigens / genetics,  physiology*
HLA-B Antigens / genetics,  physiology
Hepatitis C / drug therapy*,  physiopathology*
Logistic Models
Membrane Transport Proteins / genetics,  physiology*
Middle Aged
Polymorphism, Genetic / genetics
Treatment Outcome
Grant Support
G1001738//Medical Research Council; R01 DA033541/DA/NIDA NIH HHS; R01 DA033541/DA/NIDA NIH HHS; U19 AI0663445/AI/NIAID NIH HHS; U19 AI066345/AI/NIAID NIH HHS; U19 AI082630/AI/NIAID NIH HHS; U19 AI082630/AI/NIAID NIH HHS
Reg. No./Substance:
0/Antiviral Agents; 0/HLA Antigens; 0/HLA-B Antigens; 0/Membrane Transport Proteins; 0/tapasin

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