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RISS 인기검색어
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- 저자 : ( Tatsuji Kimura ) (검색결과 1 건)
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( Kazumoto Murata ),( Masaya Sugiyama ),( Tatsuji Kimura ),( Sachiyo Yoshio ),( Tatsuya Kanto ),( Mai Asano ),( Yoshihiko Aoki ),( Tsutomu Takeda ),( Masaaki Korenaga ),( Masatoshi Imamura ),( Naohiko 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: Genetic variation of interleukin-28B (IL28B), encoding IFN-l3, predict non-responders to pegylated interferon-α/ ribavirin (Peg-IFN/RBV) therapy in chronic hepatitis C (CHC). However, it remains unknown whether IL28B is a functional phenotype, and why it failed to predict treatment responses at 20%. Methods: Message and protein levels of IFN-l3 induced by ex vivo stimulation of peripheral blood mononuclear cells (PBMC) with toll-like receptor agonists (TLR3; poly I: C, TLR7; R-837) were measured by quantitative real-time PCR and our newly developed chemiluminescence enzyme immunoassays, and compared with the clinical data. BDCA-3 or -4+dendritic cells (DC) was negatively or positively selected by Magnet-Associated Cell Sorting. Results: We firstly found that BDCA-4+DCs were the main producers of IFN-ls when stimulated with R-837 whereas BDCA-3+DCs were main producers of IFN-ls when stimulated with poly I: C, using PBMC from healthy volunteers. We also found that detectable levels of IFN-ls were inducible using small amount of PBMC by R-837, not poly I: C. When stimulated with R-837, IFN-l3 was more robustly up-regulated in the PBMC from CHC patients with favorable genotype (TT in rs8099917, n = 59) for the response to Peg-IFN/RBV than non-TT (n = 41) whereas no differences was observed in IFN-l1 or IFNl2, which may support our GWAS data. Importantly, protein levels of IFN-l3 induced by R-837 clearly differentiated the response to Peg-IFN/RBV treatment (p = 1.0×10-10), including discrepant cases such as VR in patients with TG/GG or NVR in TT genotype. Our method more accurately predicted treatment efficacies (95.7%) than IL28B genotyping (65.2%) did. Conclusions: Genetic variations in IL28B basically affect IFNl3 production, but different amount of IFN-l3 production determines the outcomes of Peg-IFN/RBV treatment. This study, for the first time, presents compelling evidence that genetic variations in IL28B confer a functional phenotype. Our method may provide more accurate prediction for the efficacy of Peg-IFN/RBV.
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