Laura Gragnani, Elisa Fognani, Alessia Piluso, Anna Linda Zignego, Center for Systemic Manifestations of Hepatitis Viruses, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
World J Gastroenterol. 2013 Dec 21;19(47):8910-5. doi: 10.3748/wjg.v19.i47.8910.
Mixed cryoglobulinemia (MC) is the extrahepatic manifestation most strictly correlated with hepatitis C virus (HCV) infection; it is a benign autoimmune and lymphoproliferative disorder that evolves to lymphoma in 5%-10% of cases. MC is reputed to be a multistep and multifactorial process whose pathogenicity is still poorly understood. It is still unknown why only some chronically infected HCV patients develop MC and only some of these exhibit systemic symptoms (MC syndrome). Several studies have investigated the pathogenetic basis of MC and the most recent ones suggest that the virus is able to trigger such a disorder only in the presence of genetic factors that are still unknown. Here, we try to clarify the complex relationship between HCV-related MC and the host's genetic background. The data that we report are heterogeneous and sometimes even conflicting. Therefore, large, multicenter studies are clearly needed. The identification of a characteristic genetic signature of cryoglobulinemic patients would be an important step toward a personalized approach in their clinical care. The new wide-ranging genomics technologies will hopefully help to resolve these complex issues.
混合性冷球蛋白血症 (MC) 是与丙型肝炎病毒 (HCV) 感染相关性最强的肝外表现；它是一种良性的自身免疫性和淋巴增生性疾病，在 5%-10%的病例中发展为淋巴瘤。MC 被认为是一个多步骤和多因素的过程，其发病机制仍知之甚少。目前尚不清楚为什么只有一些慢性 HCV 感染患者会出现 MC，也不知道为什么只有其中一些患者会出现全身症状（MC 综合征）。有几项研究探讨了 MC 的发病基础，最近的研究表明，只有在尚未明确的遗传因素存在的情况下，病毒才能引发这种疾病。在这里，我们试图阐明与 HCV 相关的 MC 与宿主遗传背景之间的复杂关系。我们报告的数据具有异质性，有时甚至相互矛盾。因此，显然需要进行大型的、多中心的研究。确定冷球蛋白血症患者的特征性遗传特征将是其临床治疗个体化方法的重要一步。新的广泛基因组学技术有望有助于解决这些复杂问题。
