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恩替卡韦治疗慢性乙型肝炎患者时调节性T细胞和Th17细胞比率变化及与e抗原消失的关系
宋春辉,杨斌,陈黎明,张纪元*
0
(解放军302医院肝病生物治疗研究中心,北京 100039)
摘要:
目的研究恩替卡韦(ETV)治疗慢性乙型肝炎患者过程中调节性T细胞(Treg)与Th17细胞的比率(Treg/Th17)与血清中乙肝病毒e抗原(HBeAg)消失的关系。方法在应用ETV治疗的不同时间点抽取HBV感染患者及健康对照者静脉血,分离血清及外周血单个核细胞(PMBC),检测血清中乙型肝炎病毒表面标志物(HBV-M)、乙型肝炎病毒核酸定量(HBV-DNA)、丙氨酸转氨酶(ALT)、血清特异白细胞介素17(IL-17)水平以及外周血中的Treg细胞与 Th17细胞的频数。结果与HBV-DNA及Treg细胞频数的下降相对应,所有患者表现为Th17细胞频数的快速增加,以及HBcAg特异性刺激条件下IL17分泌的下降。治疗引起的HBV复制抑制能够导致Treg/Th17比率的明显下降。第4周时的Treg/Th17比率下降和其后血清HBeAg的消失关系密切。 结论病毒复制的抑制不仅减轻Th17细胞的活动而且能够快速降低Treg/Th17比率。第4周时的Treg/Th17比率有望成为预测ETV治疗慢性HBV感染患者有效性的标志。
关键词:  乙型肝炎  恩替卡韦  乙型肝炎e抗原  调节性T淋巴细胞  Th17细胞
DOI:10.3724/SP.J.1008.2011.00
投稿时间:2010-07-15修订日期:2010-12-23
基金项目:国家科技重大专项课题 (2008ZX10002-007).
Relationship of circulating Th17/Treg ratio with hepatitis B e-antigen loss in chronic HBV infection patients receiving enticarvir(ETV) antiviral treatment
SONG Chun-hui,YANG Bin,CHEN Li-ming,ZHANG Ji-yuan*
(Biological Therapy and Research Center of Liver Disease, No. 302 Hospital of PLA, Beijing 100039, China)
Abstract:
ObjectiveTo investigate the relation of Treg/Th17 ratio with HBeAg loss in chronic HBV infection patients during enticarvir antiviral treatment. MethodsThe sera and peripheral blood mononuclear cells (PBMCs) were obtained from the enrolled chronic HBV infection patients and healthy controls at different time points of enticarvir antiviral treatment. The HBV markers, HBVDNA, serum alanine transaminase(ALT), the HBVspecific IL17 levels, and the frequencies of Th17, Treg cells in PBMCs were determined. ResultsHBVDNA and Treg cell frequencies were decreased and the frequency of Th17 cells was rapidly increased in all patients; the secretion of IL17 decreased upon specific stimulation with HBcAg . Therapy induced inhibition of HBV replication led to great decrease of Treg/Th17. The decrease of Treg/Th17 ratio was closely related to loss of serum HBeAg at the fourth week. ConclusionInhibition of viral replication can not only reduce the activity of Th17 cells, but also quickly decrease the Treg/Th17 ratio. The Treg/Th17 ratio at the fourth week can serve as a marker for the effect of entacavir treatment for chronic hepatitis B.
Key words:  hepatitis B  enticarvir  hepatitis B e-antigen  regulatory T-lymphocytes  Th17 cells