Zuckerman Eli, Kessel Aharon, Slobodin Gleb, Sabo Edmond, Yeshurun Daniel, Toubi Elias
Department of Internal Medicine A Institute of Clinical Immunology, Bnai Zion Medical Center, Haifa, Israel.
J Virol. 2003 Oct;77(19):10432-6. doi: 10.1128/jvi.77.19.10432-10436.2003.
Hepatitis C virus (HCV) infection is associated with immune-mediated abnormalities and B-cell lymphoproliferation. Recently, CD81 was identified as an HCV receptor on B lymphocytes, providing a mechanism by which B cells are infected and activated by the virus. It has recently been shown that peripheral B-cell CD81 overexpression and CD5(+) subpopulation expansion correlate with HCV viral load and are associated with the development of HCV-related autoimmunity. In the present study, we assessed the effects of combination antiviral therapy (alfa interferon and ribavirin) on peripheral B-cell CD81 expression and CD5 expansion and the presence of autoimmune markers. Peripheral B-cell CD5 expression and the mean fluorescence intensity of CD81 were assessed by flow cytometry before and after treatment in 15 HCV-infected patients, in 10 untreated patients, and in 25 healthy controls. A significant posttreatment decrease in peripheral B-cell CD81 expression and disappearance of CD5(+) B-cell expansion were observed in all nine patients in whom a complete and sustained virological response was achieved (P < 0.01) (comparable to those for healthy controls). The decrease in CD81 overexpression and CD5 expansion in these patients was associated with a decrease and/or disappearance of autoimmune markers. In contrast, in nonresponders overexpression of CD81 and expansion of the CD5(+) B-cell subpopulation were not significantly changed and were comparable to those for untreated patients. In conclusion, antiviral therapy down-regulates peripheral B-cell CD81 expression and the CD5(+) population, either directly or by its effect on HCV RNA load. The overexpression of CD81 and the expansion of the population of CD5(+) peripheral B cells in HCV-infected patients may possibly play a role in the development of HCV-associated autoimmunity and lymphoproliferation.
丙型肝炎病毒（HCV）感染与免疫介导的异常及B细胞淋巴增殖有关。最近，CD81被鉴定为B淋巴细胞上的HCV受体，为病毒感染和激活B细胞提供了一种机制。最近有研究表明，外周血B细胞CD81过表达和CD5(+)亚群扩增与HCV病毒载量相关，并与HCV相关自身免疫的发展有关。在本研究中，我们评估了联合抗病毒治疗（α干扰素和利巴韦林）对外周血B细胞CD81表达、CD5扩增及自身免疫标志物存在情况的影响。通过流式细胞术对15例HCV感染患者、10例未治疗患者和25例健康对照在治疗前后的外周血B细胞CD5表达及CD81平均荧光强度进行了评估。在所有9例实现完全和持续病毒学应答的患者中，观察到外周血B细胞CD81表达在治疗后显著降低，CD5(+) B细胞扩增消失（P < 0.01）（与健康对照相当）。这些患者中CD81过表达和CD5扩增的降低与自身免疫标志物的减少和/或消失相关。相比之下，无应答者中CD81的过表达和CD5(+) B细胞亚群的扩增没有显著变化，与未治疗患者相当。总之，抗病毒治疗可直接或通过其对HCV RNA载量的影响下调外周血B细胞CD81表达和CD5(+)群体。HCV感染患者中CD81的过表达和外周血CD5(+) B细胞群体的扩增可能在HCV相关自身免疫和淋巴增殖的发展中起作用。
