HCV-related cryoglobulinemic vasculitis: an update on its etiopathogenesis and therapeutic strategies.
HCV-related cryoglobulinemic vasculitis: an update on its etiopathogenesis and therapeutic strategies.
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HCV 相关冷球蛋白血症性血管炎：其发病机制和治疗策略的最新进展。
DOI：
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发表时间：
2003
影响因子：
3.7
通讯作者：
A. Zignego
中科院分区：
文献类型：
--
作者：
C. Ferri;D. Giuggioli;M. Cazzato;M. Sebastiani;M. Mascia;A. Zignego
冷球蛋白血症性血管炎（CV）是一种免疫复合物介导的累及中小血管的系统性血管炎。在流行病学、病理学和实验室研究的基础上，丙型肝炎病毒（HCV）在超过4/5的患者中的致病作用已明确确立。CV以及其他HCV相关免疫淋巴组织增生性疾病的患病率存在很大的地理异质性。因此，未知的环境和/或遗传辅因子应有助于这些条件的发病机制。由于生物学特性，HCV基因组序列不能整合到宿主基因组中;病毒只能通过对免疫系统施加慢性刺激来间接触发免疫学改变。最近的实验室观察为我们提供了关于HCV相关CV复杂发病机制的新的重要见解。首先，HCV包膜蛋白E2能够结合B淋巴细胞上表达的CD 81分子，可能参与HCV驱动的自身免疫和淋巴增殖现象的最初步骤。HCV-E2与CD 81的相互作用可增加抗原反应性B细胞VDJ重排的发生率。一个可能的结果可能是抗凋亡Bcl-2原癌基因的激活，导致B细胞存活延长。有趣的是，t（14，18）易位沿着Bcl-2的激活已在80% HCV相关CV的B淋巴细胞中得到证实。B淋巴细胞的扩增导致了广泛的自身抗体和免疫复合物的产生，包括混合的cryobulins。CV显示出相对良性的临床过程;然而，如果与一般人群相比，其累积生存率显著更差。对于HCV相关CV的正确治疗方法，我们必须处理相互矛盾的条件：HCV感染，自身免疫和淋巴组织增生性改变。CV的治疗策略包括病因治疗、病因治疗和/或对症治疗，应根据临床症状的严重程度为单个患者量身定制。在所有情况下，必须对HCV相关CV患者进行仔细的临床监测，特别注意肿瘤并发症。
Cryoglobulinemic vasculitis (CV) is an immune-complex-mediated systemic vasculitis involving small-medium sized vessels. A causative role of hepatitis C virus (HCV) in over 4/5 patients has been definitely established on the basis of epidemiological, pathological, and laboratory studies. There is great geographical heterogeneity in the prevalence of CV as well as other HCV-related immuno-lymphoproliferative disorders. Thus, unknown environmental and/or genetic co-factors should contribute to the pathogenesis of these conditions. Due to the biological properties, HCV genomic sequences cannot be integrated into the host genome; the virus could trigger the immunological alterations only indirectly by exerting a chronic stimulus to the immune system. Recent laboratory observations gave us new important insights on the complex pathogenetic mechanism(s) of HCV-related CV. Firstly, the HCV envelop protein E2, able to bind CD81 molecule expressed on B-lymphocytes, might be involved in the first steps of HCV-driven autoimmune and lymphoproliferative phenomena. The interaction between HCV-E2 and CD81 may increase the frequency of VDJ rearrangement in antigen-reactive B-cell. One possible consequence may be the activation of anti-apoptotic Bcl-2 protoncogene that leads to extended B-cell survival. Interestingly, t(14, 18) translocation along with Bcl-2 activation have been demonstrated in B-lymphocytes of 80% HCV-related CV. The B-lymphocyte expansion is responsible for a wide autoantibody and immune-complex production, including mixed cryoglobulins. CV shows a relatively benign clinical course; however, its cumulative survival is significantly worse if compared to general population. For a correct therapeutic approach to HCV-related CV we must deal with conflicting conditions: HCV infection, autoimmune, and lymphoproliferative alterations. Therapeutic strategy of CV includes etiologic, pathogenetic, and/or symptomatic therapies, which should be tailored for the single patient according to the severity of clinical symptoms. A careful clinical monitoring of patients with HCV-related CV is mandatory in all cases, with particular attention to neoplastic complications.
影响因子：
158.5
作者：
McHutchison, JG;Gordon, SC;Albrecht, JK
通讯作者：
Albrecht, JK