Luppi M, Grazia Ferrari M, Bonaccorsi G, Longo G, Narni F, Barozzi P, Marasca R, Mussini C, Torelli G
Centre for Experimental Haematology, Department of Medical Sciences, University of Modena, Italy.
Leukemia. 1996 Feb;10(2):351-5.
Hepatitis C virus (HCV) is both hepatotropic and lymphotropic and a clear-cut association has been proposed between HCV infection and mixed cryoglobulinemia (MC), a benign lymphoproliferative disorder, which sometimes evolves into a frank malignant B cell non-Hodgkin's lymphoma (B-NHL). Moreover, in the presence of antibodies to HCV, as well as of HCV-specific genomes has been reported in the sera of over 37% patients with B-NHL, not associated with MC. Thus, we decided to perform both a serologic and a molecular study to give insights into a possible relationship between HCV infection and neoplastic lymphoproliferations. We used ELISA and RIBA tests to show that anti-HCV antibodies were present in the serum of 29 out of 69 unselected B-NHL patients (42%), while seropositivity in a healthy population was about 1%. The prevalence of anti-HCV antibodies was low in definite subsets of B lymphoid disorders, including multiple myeloma, Waldenström's macroglobulinemia and monoclonal gammopathies of undetermined significance. Then, using reverse transcriptase polymerase chain reaction, we detected HCV sequences directly in the pathologic lymph node biopsies in 13 out of 34 B-NHL cases, and in particular in six out of eight low-grade lymphomas of MALT type and in five out of eight centroblastic-centrocytic follicular lymphomas. In contrast, the peripheral blood samples from 10 B cell chronic lymphocytic leukemia patients resulted negative for the presence of HCV genomes. Similarly, viral sequences were absent in 10 T cell NHL, while only one out of the 14 Hodgkin's disease cases tested resulted positive. Finally, we used a PCR-based assay to characterize the genotypes (I-IV) present in the positive lymphomatous tissues. The presence of both serologic and molecular markers of HCV infection in a high percentage of certain types of B-NHL, not associated with cryoglobulinemia, and its absence from other lymphoproliferative diseases extends the spectrum of HCV-associated lymphoproliferations arguing in favor of some role of this viral infection in the pathogenesis of the malignant proliferation of definite B lymphoid populations.
丙型肝炎病毒（HCV）具有嗜肝性和嗜淋巴细胞性，并且有人提出HCV感染与混合性冷球蛋白血症（MC）之间存在明确关联，MC是一种良性淋巴增殖性疾病，有时会发展为明显的恶性B细胞非霍奇金淋巴瘤（B-NHL）。此外，在超过37%的非MC相关B-NHL患者血清中已报告存在抗HCV抗体以及HCV特异性基因组。因此，我们决定进行血清学和分子研究，以深入了解HCV感染与肿瘤性淋巴增殖之间的可能关系。我们使用酶联免疫吸附测定（ELISA）和重组免疫印迹分析（RIBA）试验表明，69例未经选择的B-NHL患者中有29例（42%）血清中存在抗HCV抗体，而健康人群中的血清阳性率约为1%。在包括多发性骨髓瘤、华氏巨球蛋白血症和意义未明的单克隆丙种球蛋白病在内的特定B淋巴细胞疾病亚组中，抗HCV抗体的患病率较低。然后，我们使用逆转录聚合酶链反应，在34例B-NHL病例中的13例病理淋巴结活检组织中直接检测到HCV序列，特别是在8例MALT型低级别淋巴瘤中的6例以及8例中心母细胞-中心细胞性滤泡性淋巴瘤中的5例中检测到。相比之下，10例B细胞慢性淋巴细胞白血病患者的外周血样本检测HCV基因组呈阴性。同样，10例T细胞非霍奇金淋巴瘤中未检测到病毒序列，而在14例接受检测的霍奇金病病例中只有1例呈阳性。最后，我们使用基于聚合酶链反应的分析方法来鉴定阳性淋巴瘤组织中存在的基因型（I-IV）。在高比例的某些类型的非冷球蛋白血症相关B-NHL中存在HCV感染的血清学和分子标志物，而在其他淋巴增殖性疾病中不存在，这扩展了HCV相关淋巴增殖的范围，表明这种病毒感染在特定B淋巴细胞群体恶性增殖的发病机制中起到了一定作用。
