The Viral Load of Epstein-Barr Virus (EBV) DNA in Peripheral Blood Predicts for Biological and Clinical Characteristics in Hodgkin Lymphoma
The Viral Load of Epstein-Barr Virus (EBV) DNA in Peripheral Blood Predicts for Biological and Clinical Characteristics in Hodgkin Lymphoma
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DOI：
10.1158/1078-0432.ccr-10-3327
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发表时间：
2011-05-01
影响因子：
11.5
通讯作者：
Larocca, Luigi M.
中科院分区：
文献类型：
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作者：
Hohaus, Stefan;Santangelo, Rosaria;Larocca, Luigi M.
目的：Epstein-Barr病毒（EBV）存在于西方国家20% - 40%霍奇金淋巴瘤（HL）患者的恶性霍奇金/Reed-Sternberg （HRS）细胞。我们对检测和定量无细胞血浆EBV-DNA作为ebv相关HL的生物学和临床特征的指标感兴趣。实验设计：EBV在诊断时通过实时PCR检测EBNA （EB核抗原）区域（n = 93），在HRS细胞中通过EBV编码小rna的原位杂交（EBER; n = 63）检测外周血区（全血、血浆和单核细胞）。这些数据与组织学和临床特征、EBV血清学、循环无细胞DNA和白细胞介素(IL)-6水平相关。结果：血浆中EBV- dna检测在预测EBV相关性方面具有高特异性（90%），但相对较低的敏感性（65%）。在疾病晚期、年龄较大且存在b症状、国际预后评分大于2分的患者中，病毒载量较高。HRS细胞中EBV的存在和较高的血浆EBV- dna拷贝数与淋巴结活检中肿瘤浸润性CD68+巨噬细胞的频率增加相关。血浆EBV-DNA载量与循环游离DNA和IL-6水平相关，与淋巴细胞计数和EBNA1抗体滴度呈负相关。结论：虽然外周血EBV-DNA的存在不能作为EBER的替代标志物，但在HL诊断时，血浆EBV-DNA载量是疾病活动性和与阴性预后相关的生物学特征的指标。此外，与EBNA1抗体滴度和淋巴细胞计数的负相关可能表明免疫监视降低，有利于EBV-HRS细胞在HL中的扩增。临床癌症研究；17 (9);2885 - 92。(c) 2011年aacr。
Purpose: The Epstein-Barr virus (EBV) is present in the malignant Hodgkin/Reed-Sternberg (HRS) cells of 20% to 40% cases of Hodgkin lymphoma (HL) in Western countries. We were interested in the detection and quantification of cell-free plasma EBV-DNA as an indicator of biological and clinical characteristics in EBV-associated HL.Experimental Design: EBV was detected in peripheral blood compartments (whole blood, plasma, and mononuclear cells) at diagnosis by real-time PCR for the EBNA (EB nuclear antigen) region (n = 93) and in HRS cells by in situ hybridization for EBV-encoded small RNAs (EBER; n 63). These data were correlated to histological and clinical characteristics, EBV serology, circulating cell-free DNA, and interleukin (IL)-6 levels.Results: Detection of EBV-DNA in plasma had a high specificity (90%), but a relatively low sensitivity (65%) to predict for EBV association. The viral load was higher in patients with advanced stage disease, older age in the presence of B-symptoms, and international prognostic score more than 2. The presence of EBV in HRS cells and higher plasma EBV-DNA copy numbers correlated to an increased frequency of tumor-infiltrating CD68+ macrophages in lymph node biopsies. Plasma EBV-DNA load correlated to circulating cell-free DNA and IL-6 levels, and inversely correlated to lymphocyte counts and EBNA1 antibody titers.Conclusion: Although the presence of EBV-DNA in peripheral blood cannot be regarded as a surrogate marker for EBER, the plasma EBV-DNA load at HL diagnosis is an indicator of disease activity and biological characteristics associated with negative prognosis. Moreover, the inverse correlation to EBNA1 antibody titers and lymphocyte counts may indicate a reduction in immunosurveillance, favoring the expansion of EBV-HRS cells in HL. Clin Cancer Res; 17(9); 2885-92. (C) 2011 AACR.