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Interferon- ? -Induced Changes to Natural Killer Cells Are Associated with the Treatment Outcomes in Patients with HCV Infections.

ABSTRACT: Aim. We analyzed the pretreatment natural killer (NK) cell functions with the aim of predicting the sustained virological response (SVR) or the interleukin (IL) 28B polymorphism that is strongly associated with the treatment response. Methods. The peripheral NK cells from chronic hepatitis patients with HCV genotype 1 and high virus titers were activated using a Toll-like receptor (TLR) 4 ligand and IFN- ? . The cell surface markers were evaluated using a flow cytometric analysis, and IFN- ? production was evaluated using an enzyme-linked immunosorbent assay (ELISA). The genotyping of the polymorphisms in the IL28B gene region (rs8099917) on chromosome 19 was performed on the DNA collected from each patient. Results. The production of IFN- ? was significantly higher in the SVR patients compared with the no-response (NR) patients, whereas the cell surface markers were similar between the SVR and the NR patients. There were no significant differences found in the IL28B genotype distribution associated with the production of IFN- ? . Conclusion. Differences in the NK cell functions were observed between the SVR patients and the NR patients, suggesting that NK cells play a potential role in the treatment response independent of the IL28B genotype.

SUBMITTER: Shimoda S

PROVIDER: S-EPMC3755421 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Interferon- α -Induced Changes to Natural Killer Cells Are Associated with the Treatment Outcomes in Patients with HCV Infections.

Shimoda Shinji S Sumida Kosuke K Iwasaka Sho S Hisamoto Satomi S Tanimoto Hironori H Nomura Hideyuki H Dohmen Kazufumi K Takahashi Kazuhiro K Kawano Akira A Ogawa Eiichi E Furusyo Norihiro N Akashi Koichi K Hayashi Jun J

Hepatitis research and treatment 20130813

Aim. We analyzed the pretreatment natural killer (NK) cell functions with the aim of predicting the sustained virological response (SVR) or the interleukin (IL) 28B polymorphism that is strongly associated with the treatment response. Methods. The peripheral NK cells from chronic hepatitis patients with HCV genotype 1 and high virus titers were activated using a Toll-like receptor (TLR) 4 ligand and IFN- α . The cell surface markers were evaluated using a flow cytometric analysis, and IFN- γ pro ...[more]

PMID: 23997950

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Project description:BackgroundTo investigate the changes of natural killer (NK) cell phenotype in the interferon alpha (IFN-α) treatment of chronic hepatitis B (CHB) and its relationship with clinical indicators.MethodsThe CHB patients who did not receive any antiviral treatment were set as initial treatment group and used pegylated interferon alpha (PEG-IFN α). Peripheral blood samples were collected at baseline, 4 weeks, and 12-24 weeks. For IFN-treated patients who entered the plateau were set as plateau group, and PEG-IFN α was discontinued and resumed after an interval of 12-24 weeks. Besides, we also enrolled some patients who had received oral drug for more than 6 months as oral drug group without follow up. Peripheral blood was collected during the plateau period, which was set as baseline, and after 12-24 weeks of intermittent treatment, and after 12-24 weeks of additional treatment with PEG-IFN α. The aim of the collection was to detect hepatitis B virus (HBV) virology, serology and biochemical indicators, and the NK cell related phenotype was detected by flow cytometry.ResultsIn the plateau group, subgroup of CD69+CD56dim was higher with statistical significance when comparing with the initial treatment group and oral drug group [10.49 (5.27, 19.07) vs 5.03 (3.67, 8.58), Z = -3.11, P = 0.002; 10.49 (5.27, 19.07) vs 4.04 (1.90, 7.26), Z = -5.30, P < 0.001)]. CD57+CD56dim was significantly lower than that in initial treatment group and oral drug group respectively [68.42±10.37 vs 55.85±12.87, t = 5.84, P < 0.001; 76.38±9.49 vs 55.85±12.87, t = -9.65, P < 0.001]. The CD56brightCD16- subgroup in the plateau group was higher with statistical significance compared with initial treatment group and oral drug group respectively [11.64 (6.05, 19.61) vs 3.58 (1.94, 5.60), Z = -6.35, P < 0.001; 11.64 (6.05, 19.61) vs 2.37 (1.70, 4.30), Z = -7.74, P < 0.001)]. CD57+CD56dim in the plateau group had a significant higher percentage than that at baseline after IFN discontinuation for 12-24 weeks (55.85±12.87 vs 65.95±12.94, t = -2.78, P = 0.011).ConclusionDuring the long-term treatment of IFN, the killer subgroup of NK cells is continuously depleted, leading to the differentiation of the regulatory subgroup into the killer subgroup. In the killing subgroup, although the number is continuously depleted, the activity of the subgroup is continuously increased. In the plateau phase, after stopping IFN for a period of time, the number of NK cell subsets would gradually recover, but was still lower than that in the initial treatment group.

Dataset Information

Interferon- ? -Induced Changes to Natural Killer Cells Are Associated with the Treatment Outcomes in Patients with HCV Infections.

Publications

Interferon- α -Induced Changes to Natural Killer Cells Are Associated with the Treatment Outcomes in Patients with HCV Infections.

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