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[抗病毒治疗对慢性乙型肝炎患者病毒特异性T细胞反应性的影响]

[The impact of antiviral therapy on virus-specific T-cell reactivity in patients with chronic hepatitis B].

作者信息

Feng Xia, Yan Hui-ping, Liao Hui-yu, Liu Yan-min, Huang Yun-li, Zhang Guo-yuan, Lin Fang, Zhang Xin, Zhao Yan, Zhang Hai-ping, Wang Shuang, Wang Yi

机构信息

Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2012 Mar 20;92(11):739-42.

Abstract

OBJECTIVE

To investigated the impact of viral load decline on virus-specific T-cell reactivity on patients with chronic hepatitis B.

METHODS

23 cases of patients with chronic hepatitis B were recruited randomized to therapy with nucleoside analogue or alpha interferon from January 2009 to April 2010. Peripheral blood mononuclear cells (PBMCs) were collected longitudinally at baseline and the time of HBV DNA undetected. T-cell reactivity to HBV core antigens were tested using Elispot assays and Luminex.

RESULTS

(1) The frequency of T cell reactivity induced by HBcAg in patients with chronic hepatitis B were 91.3% at the time of HBV DNA undetected, which significantly higher than The frequency of 69.6% at baseline. The frequency between nucleoside analogue treatment group and alpha interferon treatment group was no significant difference. (2) The average response magnitude was expressed as spot forming unit (SFU) per million input cells. SFU of T cell responses to HBcAg was 120 SFU/10(6) PBMCs at baseline, much lower than SFU of 1060 SFU/10(6) PBMCs at the time of HBV DNA undetected. No significant difference between patients with negative T cell reactivity at baseline and patients with positive T cell reactivity at baseline was found. In patients with initial virological response (IVR) to therapy and patients with early virological response (EVR), no significant difference was found in the magnitude at baseline as well as at the time of HBV DNA undetected. (3) The average response magnitude of nucleoside analogue treatment group was 1713 SFU/10(6) PBMCs at the time the time of HBV DNA undetected, higher than 189 SFU/10(6) PBMCs at baseline. But in interferon treatment group, the average response magnitude was no significant difference, 120 SFU/10(6) PBMCs at the baseline and 305 SFU/10(6) PBMCs at the time the time of HBV DNA undetected respectively. The average response magnitude in nucleoside analogue treatment group was greater than that in interferon treatment group. (4) As to compare difference of IFN-γ concentration in supernatant of T cell culture solution stimulated by HBcAg, IFN-γ secreted by T cell at the time of HBV DNA undetected was clearly higher than IFN-γ secreted at baseline, (38 ± 9) ng/L and (90 ± 9) ng/L respectively.

CONCLUSIONS

Antiviral therapy made profit to improve virus-specific T-cell reactivity in patients with chronic hepatitis B, suggesting the importance to investigate HBV specific T cell responses.

摘要

目的

研究病毒载量下降对慢性乙型肝炎患者病毒特异性T细胞反应性的影响。

方法

招募23例慢性乙型肝炎患者,于2009年1月至2010年4月随机接受核苷类似物或α干扰素治疗。在基线和HBV DNA未检测到时纵向收集外周血单个核细胞(PBMC)。使用酶联免疫斑点试验(Elispot)和Luminex检测T细胞对乙肝核心抗原的反应性。

结果

(1)慢性乙型肝炎患者在HBV DNA未检测到时,由乙肝核心抗原诱导的T细胞反应频率为91.3%,显著高于基线时的69.6%。核苷类似物治疗组和α干扰素治疗组之间的频率无显著差异。(2)平均反应强度以每百万输入细胞的斑点形成单位(SFU)表示。T细胞对乙肝核心抗原反应的SFU在基线时为120 SFU/10⁶ PBMC,远低于HBV DNA未检测到时的1060 SFU/10⁶ PBMC。基线时T细胞反应阴性的患者与基线时T细胞反应阳性的患者之间未发现显著差异。在对治疗有初始病毒学应答(IVR)和早期病毒学应答(EVR)的患者中,基线时以及HBV DNA未检测到时的反应强度均无显著差异。(3)核苷类似物治疗组在HBV DNA未检测到时的平均反应强度为1713 SFU/10⁶ PBMC,高于基线时的189 SFU/10⁶ PBMC。但干扰素治疗组的平均反应强度无显著差异,基线时为120 SFU/10⁶ PBMC,HBV DNA未检测到时为305 SFU/10⁶ PBMC。核苷类似物治疗组的平均反应强度大于干扰素治疗组。(4)比较乙肝核心抗原刺激的T细胞培养液上清中IFN-γ浓度的差异,HBV DNA未检测到时T细胞分泌的IFN-γ明显高于基线时分泌的IFN-γ,分别为(38±9)ng/L和(90±9)ng/L。

结论

抗病毒治疗有利于提高慢性乙型肝炎患者的病毒特异性T细胞反应性,提示研究HBV特异性T细胞反应的重要性。

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