title: Influence of ethnicity in the outcome of hepatitis C virus infection and cellular immune response.
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 gamma (IFN-gamma) 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.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Jason
authors.initials: J
authors.lastname: Stadanlick
authors.forename: Fusao
authors.initials: F
authors.lastname: Ikeda
authors.forename: Colleen
authors.initials: C
authors.lastname: Brensinger
authors.forename: Emma E
authors.initials: EE
authors.lastname: Furth
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Alter
authors.forename: Kyong-Mi
authors.initials: KM
authors.lastname: Chang
mesh_terms: D044383:Black People; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D018936:Hepatitis C Antigens / Q000235:genetics / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000208:ethnology* / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D008099:Liver / Q000503:physiopathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology; D044465:White People; D001741:Black or African American
chemical_list: D018936:Hepatitis C Antigens; D007371:Interferon-gamma