Influence of ethnicity in the outcome of hepatitis C virus infection and cellular immune response

Authors

  • Kazushi Sugimoto,

    1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA
    2. Philadelphia Veterans Administration Medical Center, Philadelphia, PA
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  • Jason Stadanlick,

    1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA
    2. Philadelphia Veterans Administration Medical Center, Philadelphia, PA
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  • Fusao Ikeda,

    1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA
    2. Philadelphia Veterans Administration Medical Center, Philadelphia, PA
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  • Colleen Brensinger,

    1. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA
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  • Emma E. Furth,

    1. Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA
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  • Harvey J. Alter,

    1. Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD
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  • Kyong-Mi Chang University and Woodland Ave.

    Corresponding author
    1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA
    2. Philadelphia Veterans Administration Medical Center, Philadelphia, PA
    • Philadelphia, PA 19104; fax: 215-823-4394
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Abstract

This study was performed to examine the immunologic basis for the apparent ethnic difference in clinical outcome of hepatitis C virus (HCV) infection between African Americans (AA) and Caucasian Americans (CA). To this end, we recruited 99 chronically HCV-infected and 31 spontaneously HCV-cleared subjects for clinical, virologic, and immunologic analysis. In particular, CD4-proliferative T-cell response to genotype 1–derived HCV antigens (core, NS3-NS5) was examined in 82 patients chronically infected with genotype 1 (54 AA, 28 CA) and in all HCV-cleared subjects (14 AA, 17 CA). HCV-specific Th1 response also was examined in 52 chronic and 13 recovered subjects. Our results showed that HCV clearance was associated with a vigorous HCV-specific Th1 response irrespective of ethnic origin. Although the HCV-specific CD4 T-cell response clearly was weaker during chronic infection, AA ethnicity in this setting was associated with a significantly greater CD4-proliferative T-cell response to HCV, particularly to the nonstructural antigens (22% AA vs. 0% CA, P = .007) as well as better clinical parameters of liver disease. Interestingly, most HCV-specific CD4 T-cell proliferative responses in AA patients were unaccompanied by concurrent interferon γ (IFN-γ) production, suggesting a dysregulated virus-specific, CD4 T-cell effector function during chronic HCV infection. In conclusion, our results suggest that host ethnicity does influence the clinical outcome and antiviral T-cell response during HCV infection. AA ethnicity is associated with a more robust antiviral CD4 T-cell response than CA ethnicity, although these T cells are limited in direct virus or disease control due to their dysfunctional nature.

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