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慢性丙型肝炎患者基于干扰素-α的抗病毒治疗期间淋巴细胞亚群上CD81表达的动态变化

Dynamics of CD81 expression on lymphocyte subsets during interferon-alpha-based antiviral treatment of patients with chronic hepatitis C.

作者信息

Kronenberger Bernd, Herrmann Eva, Hofmann W Peter, Wedemeyer Heiner, Sester Martina, Mihm Ulrike, Ghaliai Temam, Zeuzem Stefan, Sarrazin Christoph

机构信息

klinik Für Innere Medizin II, Universitätsklinikum des Saarlandes, Kirrberger Strasse, D-66421 Homburg/Saar, Germany.

出版信息

J Leukoc Biol. 2006 Aug;80(2):298-308. doi: 10.1189/jlb.0106047. Epub 2006 May 30.

Abstract

CD81 is a hepatitis C virus (HCV) coreceptor with important functions in lymphocytes. During treatment, CD81 expression may be changed directly by the antiviral therapy or indirectly by reduction of the HCV serum level. The regulation of CD81 on lymphocyte subtypes has not been investigated so far and may be relevant for the control of viral infection and treatment response. CD81 was analyzed by flow cytometry in CD8(+), CD4(+), CD19(+), and CD56(+) lymphocyte subtypes from 20 patients with chronic hepatitis C before, during, and after antiviral treatment with pegylated interferon-alpha (IFN-alpha) and ribavirin. A sustained virologic response (SVR) was achieved in 11 patients. Dynamics of CD81 were investigated in correlation with HCV-RNA dynamics and the outcome of therapy. During treatment, the following typical patterns of CD81 regulation were observed: down-regulation on CD8(+) T cells (P = 0.022) and most significantly, on CD56(+) natural killer cells (P < 0.001), transient up-regulation on CD19(+) B cells (P = 0.006), and weak and late down-regulation on CD4(+) T cells (P = 0.028). During treatment, CD81 expression was not associated with the HCV-RNA serum level on all lymphocyte subtypes. After end of treatment, CD81 increased again in CD8(+) and CD56(+) cells (P = 0.001, P = 0.002). On CD8(+) T cells post-treatment, CD81 remained lower in patients who achieved a SVR compared with patients who failed to eliminate HCV after treatment (P = 0.033). Lymphocyte subsets show different patterns of CD81 response before and during antiviral treatment, which are associated with administration of IFN-alpha and antiviral response.

摘要

CD81是丙型肝炎病毒(HCV)的共受体,在淋巴细胞中具有重要功能。治疗期间,CD81表达可能直接受抗病毒治疗影响而改变,或因HCV血清水平降低而间接改变。目前尚未研究CD81对淋巴细胞亚群的调节作用,但其可能与病毒感染的控制及治疗反应相关。采用流式细胞术分析了20例慢性丙型肝炎患者在聚乙二醇化干扰素-α(IFN-α)和利巴韦林抗病毒治疗前、治疗期间及治疗后的CD8(+)、CD4(+)、CD19(+)和CD56(+)淋巴细胞亚群中的CD81。11例患者实现了持续病毒学应答(SVR)。研究了CD81动态变化与HCV-RNA动态变化及治疗结果的相关性。治疗期间,观察到以下典型的CD81调节模式:CD8(+) T细胞上CD81下调(P = 0.022),最显著的是CD56(+)自然杀伤细胞上CD81下调(P < 0.001),CD19(+) B细胞上CD81短暂上调(P = 0.006),CD4(+) T细胞上CD81微弱且延迟下调(P = 0.028)。治疗期间,所有淋巴细胞亚群的CD81表达均与HCV-RNA血清水平无关。治疗结束后,CD8(+)和CD56(+)细胞中的CD81再次升高(P = 0.001,P = 0.002)。治疗后,在CD8(+) T细胞上,实现SVR的患者的CD81水平低于治疗后未清除HCV的患者(P = 0.033)。淋巴细胞亚群在抗病毒治疗前和治疗期间表现出不同的CD81反应模式,这与IFN-α的给药及抗病毒反应相关。

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