Landau Dan-Avi, Saadoun David, Calabrese Leonard H, Cacoub Patrice
Université Pierre et Marie Curie-Paris 6, CNRS, UMR 7087, Paris, F-75013 France.
Autoimmun Rev. 2007 Sep;6(8):581-7. doi: 10.1016/j.autrev.2007.03.010. Epub 2007 Apr 19.
Hepatitis C virus (HCV) has been shown in epidemiologic studies to be associated with immune system disorders. Primarily disorders that stem from B-cell regulatory control disturbance, such as mixed cryoglobulinemia (MC) and non-Hodgkin's lymphoma (NHL). The causative role of HCV in these disorders is supported by the response to anti-viral treatment. The understanding of the pathophysiological process leading from HCV infection to B-cell clonal expansion has improved significantly. Data supports an antigen-driven indirect stimulation of clonal expansion model, leading from oligoclonal to monoclonal expansion and in some instances to frank malignancy. HCV-E2 antigen has been suggested as a candidate antigen as well as NS3. Binding of the B-cell receptor by viral antigens coupled with direct binding of CD-81 by HCV-E2 has been shown to provide a strong proliferative signal. Additional regulatory elements are also affected in HCV-related B-cell clonal expansion, including the Fas and BLyS signaling mechanisms. Finally, genetic events such as bcl-2 rearrangement may also be involved in clonal expansion. In this review, evidence linking HCV with MC and NHL, as well as known events in the pathophysiological process are described.
流行病学研究表明，丙型肝炎病毒（HCV）与免疫系统紊乱有关。主要是源于B细胞调节控制紊乱的疾病，如混合性冷球蛋白血症（MC）和非霍奇金淋巴瘤（NHL）。抗病毒治疗的反应支持了HCV在这些疾病中的致病作用。对从HCV感染到B细胞克隆性扩增的病理生理过程的理解有了显著提高。数据支持一种抗原驱动的间接刺激克隆性扩增模型，从寡克隆扩增到单克隆扩增，在某些情况下发展为明显的恶性肿瘤。HCV-E2抗原以及NS3已被认为是候选抗原。病毒抗原与B细胞受体结合以及HCV-E2与CD-81直接结合已被证明可提供强烈的增殖信号。在HCV相关的B细胞克隆性扩增中，其他调节元件也受到影响，包括Fas和BLyS信号机制。最后，诸如bcl-2重排等基因事件也可能参与克隆性扩增。在这篇综述中，描述了将HCV与MC和NHL联系起来的证据以及病理生理过程中的已知事件。
