title: IL28B genetic variation and hepatitis C virus-specific CD4(+)  T-cell responses in anti-HCV-positive blood donors.
abstract: Epidemiological, viral and host factors are associated with the outcome of hepatitis C virus (HCV) infection, and strong host immune responses against HCV favour viral clearance. Recently, genome-wide association studies have shown a strong correlation between single-nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene and spontaneous or treatment-induced HCV clearance. We have investigated whether protective IL28B genetic variants are associated with HCV-specific T-cell responses among Spanish blood donors. The rs12979860 IL28B haplotype was determined in 69 anti-HCV-positive blood donors (21 HCV RNA negative and 48 HCV RNA positive) and 30 seronegative donors. In all cases, HCV-specific CD4(+) T-cell responses to HCV recombinant proteins (core, NS3 and NS3 helicase) were assessed by ex vivo interferon-γ ELISpot assay. The rs12979860-CC genotype was highly overrepresented in donors with spontaneous HCV clearance when compared to those with chronic infection (76.2%vs 29.2%, P < 0.001; odds ratio, 7.77; 95% confidence interval, 2.4-25.3, P < 0.001). HCV-specific CD4(+) T-cell responses were detected in 16 (76.2%) spontaneous resolvers especially towards nonstructural proteins, but with no correlation with IL28B genotype. Chronic individuals had a significantly lower overall T-cell response again irrespective of IL28B genotype. When spontaneous resolvers and chronic individuals were stratified according to their IL28B genotype, significantly stronger T-cell responses were only observed among those with non-CC haplotypes. Although the protective rs12979860 IL28B CC genotype is associated with spontaneous HCV clearance, stronger CD4(+) T-cell responses towards NS3 were only evident among those with non-CC haplotypes.
authors.affiliation: Transfusion Safety Laboratory, Banc de Sang i Teixits, Servei Català de la Salut, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Bes
authors.forename: S
authors.initials: S
authors.lastname: Sauleda
authors.forename: I
authors.initials: I
authors.lastname: Campos-Varela
authors.forename: F
authors.initials: F
authors.lastname: Rodriguez-Frias
authors.forename: N
authors.initials: N
authors.lastname: Casamitjana
authors.forename: M
authors.initials: M
authors.lastname: Homs
authors.forename: M
authors.initials: M
authors.lastname: Piron
authors.forename: J
authors.initials: J
authors.lastname: Quer
authors.forename: D
authors.initials: D
authors.lastname: Tabernero
authors.forename: J
authors.initials: J
authors.lastname: Guardia
authors.forename: L
authors.initials: L
authors.lastname: Puig
authors.forename: J I
authors.initials: JI
authors.lastname: Esteban
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D001782:Blood Donors; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013030:Spain; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000956:Antigens, Viral; D007371:Interferon-gamma; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda