Bumbea H, Vladareanu A M, Vintilescu A, Radesi S, Ciufu C, Onisai M, Baluta C, Begu M, Dobrea C, Arama V, Streinu-Cercel A, Arama S
Hematology Department, Universitary Emergency Hospital, Bucharest, Romania.
J Med Life. 2011 Aug 15;4(3):256-63. Epub 2011 Aug 25.
Chronic lymphoproliferative disorders (CLD) are frequently found in patients with hepatitis viral infections, which can lead to changes in pathogenesis. Hepatitis viruses are hepatotrope viruses, potentially lymphotrope and also potentially oncogenic (hepatocellular carcinoma) viruses. HBV and HCV are involved in autoimmune disorders and in the ethiopathogeny of chronic lymphoproliferative disorders.
Detection of immunophenotype changes of malignant lymphocytes in CLD--especially CLL--associated with hepatitis viral infections.
Bone marrow aspirate, peripheral blood samples on EDTA were available for analysis from 58 patients from a follow-up schedule of the Department of Hematology SUUB from March 2008 until June 2009. The patients were diagnosed with chronic lymphoproliferative disorders associated with hepatitis virus B/C/D infections. A group of 28 consecutive unselected patients with CLL who met the diagnostic criteria of the National Cancer Institute-Working Group (NCI NCIWG), and associated hepatitis viral infection (v-CLL) were studied for the expression of several immunophenotypical markers, in comparison to CLL patients without viral infection (control group). Immunophenotyping analysis was performed on a FACS Calibur flowcytometer with a large panel according to EGIL/WHO recommendations. The diagnosis was completed after the histological and immunochemical analysis from tumoral lesions.
Demographics characteristics--male/female ratio 1/2, average age 64 years. Disease type: 90% B-CLD, 5% T-CLD, 5% Hodgkin's disease. The viral infections: 58.53% HCV, 34.41% HBV, 2.43% HBV+HDV, 2.43% HCV+HDV, 2.43% HBV+HCV+HDV. We found in CLL with viral coinfection (v-CLL) cases an elevated expression of B-cell markers--CD19 (Md95/92), CD20 (Md 90/39), CD79b (Md58/31), CD23 (Md67/37). Poor prognosis markers have a higher expression in v-CLL: CD38 (Md49/24), Bcl2 (Md 46/5), cyclin D19 (Md 11/0.5). No change in ZAP-70 expression was observed: Md 59.5/59.1.
Hepatitis viruses could be involved in the pathogenesis of CLD, but as a trigger for a more aggressive outcome. Higher expression of B-cell markers CD19, CD20 in CLL with viral infection suggests a change to atypical CLL, sustained by elevated expression of known poor prognosis markers bcl-2, cyclin D1 and CD38. Lack of ZAP-70 expression could be explained by a strong correlation with a basic unmutated IgVH status, not related to the viral infection. We found a higher frequency of HCV infection in patients with CLD and especially in CLL patients, which were analyzed extensively for immunophenotypical changes. In the present study, we demonstrated that this CD5+ B cell population with clonal expansion, defining CLL patients, has a different immunophenotype, probably related to the hepatitis viral infection.
慢性淋巴细胞增殖性疾病（CLD）在病毒性肝炎患者中很常见，这可能导致发病机制的改变。肝炎病毒是嗜肝病毒，可能具有嗜淋巴细胞性，也可能是潜在的致癌（肝细胞癌）病毒。HBV和HCV与自身免疫性疾病以及慢性淋巴细胞增殖性疾病的发病机制有关。
检测与肝炎病毒感染相关的CLD（尤其是CLL）中恶性淋巴细胞的免疫表型变化。
从2008年3月至2009年6月血液学系SUUB的随访计划中选取58例患者的骨髓穿刺液和EDTA抗凝外周血样本进行分析。这些患者被诊断为与乙型/丙型/丁型肝炎病毒感染相关的慢性淋巴细胞增殖性疾病。将一组连续的28例符合美国国立癌症研究所工作组（NCI NCIWG）诊断标准且伴有肝炎病毒感染的未经选择的CLL患者（v-CLL）与无病毒感染的CLL患者（对照组）进行比较，研究几种免疫表型标志物的表达情况。根据EGIL/WHO建议，在配备大检测板的FACS Calibur流式细胞仪上进行免疫表型分析。肿瘤病变经组织学和免疫化学分析后完成诊断。
人口统计学特征——男女比例为1/2，平均年龄64岁。疾病类型：90%为B-CLD，5%为T-CLD，5%为霍奇金病。病毒感染情况：58.53%为HCV，34.41%为HBV，2.43%为HBV + HDV，2.43%为HCV + HDV，2.43%为HBV + HCV + HDV。我们发现，在合并病毒感染的CLL（v-CLL）病例中，B细胞标志物——CD19（中位数95/92）、CD20（中位数90/39）、CD79b（中位数58/31）、CD23（中位数67/37）的表达升高。预后不良标志物在v-CLL中的表达更高：CD38（中位数49/24）、Bcl2（中位数46/5）、细胞周期蛋白D19（中位数11/0.5）。未观察到ZAP-70表达的变化：中位数59.5/59.1。
肝炎病毒可能参与CLD的发病机制，但作为更具侵袭性结局的触发因素。病毒感染的CLL中B细胞标志物CD19、CD20的高表达提示向非典型CLL转变，这由已知预后不良标志物bcl-2、细胞周期蛋白D1和CD38的高表达所维持。ZAP-70表达缺失可能是由于与基本未突变的IgVH状态高度相关，而与病毒感染无关。我们发现CLD患者尤其是CLL患者中HCV感染频率更高，对这些患者进行了广泛的免疫表型变化分析。在本研究中，我们证明定义CLL患者的这种具有克隆扩增的CD5 + B细胞群体具有不同的免疫表型，可能与肝炎病毒感染有关。
