IL28B genetic variation and hepatitis C virus-specific CD4(+) T-cell responses in anti-HCV-positive blood donors.
| Autor: | Bes M; Transfusion Safety Laboratory, Banc de Sang i Teixits, Servei Català de la Salut, Barcelona, Spain., Sauleda S, Campos-Varela I, Rodriguez-Frias F, Casamitjana N, Homs M, Piron M, Quer J, Tabernero D, Guardia J, Puig L, Esteban JI |
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| Jazyk: | angličtina |
| Zdroj: | Journal of viral hepatitis [J Viral Hepat] 2012 Dec; Vol. 19 (12), pp. 867-71. Date of Electronic Publication: 2012 Jul 04. |
| DOI: | 10.1111/j.1365-2893.2012.01631.x |
| Abstrakt: | 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. (© 2012 Blackwell Publishing Ltd.) |
| Databáze: | MEDLINE |
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