Epstein-Barr virus infection and risk of lymphoma: Immunoblot analysis of antibody responses against EBV-related proteins in a large series of lymphoma subjects and matched controls
Epstein-Barr virus infection and risk of lymphoma: Immunoblot analysis of antibody responses against EBV-related proteins in a large series of lymphoma subjects and matched controls
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DOI：
10.1002/ijc.22857
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发表时间：
2007-10-15
影响因子：
6.4
通讯作者：
Middeldorp, Jaap M.
中科院分区：
文献类型：
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作者：
de Sanjose, Silvia;Bosch, Ramon;Middeldorp, Jaap M.
EB病毒(Epstein-Barr Virus，EBV)一直与不同的淋巴增生性恶性肿瘤有关，在大多数EBV癌症患者中都发现了异常的EBV抗体模式。我们在一项多中心病例对照研究中评估了EBV感染的异常反应血清学模式(Ab_EBV)的检测和淋巴瘤的风险。研究开始时收集了来自西班牙、法国、德国、捷克、意大利的1085例淋巴瘤病例的血清样本，以及1153名年龄、性别和国家匹配的对照组。以EB病毒免疫优势表位EBNA1(BKRF1)和VCA-p18(BFRF3)为基础，建立基于多肽的双抗体夹心酶联免疫吸附试验(EL ISA)，评价EB病毒免疫球蛋白G(IgG)的血清状态。此外，免疫印迹分析评估了EBV早期抗原(EA)、EBNA1、VCA-p18、VCA-p40(BdRF1)和Zebra(BZLF1)的不同抗体多样性。慢性活动性EBV感染和EBV活性异常的患者以异常反应模式(Ab_EBV)为特征。在2,238名纳入研究的受试者中，有20.9%的人观察到了ABEBV，与对照人群相比，呈现ABEBV的病例比例增加(23.9%vs.18.0%p=0.001)。AB_EBV阳性是所有淋巴瘤合并的危险因素(优势比[OR]=1.42，95%可信区间[CI]=1.15~1.74)，尤其是慢性淋巴细胞白血病(OR=2.96，95%CI=2.22~3.95)。滤泡性淋巴瘤的abEBV水平较低(OR=0.38，95%-CI=0.15~0.98)。EBV可能与临床免疫活性受试者中更多的淋巴瘤有关，可能是由于对EBV潜伏感染的潜在免疫控制的丧失所致。AB_EBV也是探索EBV失衡先于或平行于可能的EBV相关致癌事件的有用方法。(C)2007年Wiley-Liss，Inc.
Epstein-Barr Virus (EBV) is consistently associated with distinct lymphoproliferative malignancies and aberrant EBV antibody patterns are found in most EBV cancer patients. We evaluate the detection of an abnormal reactive serological pattern to EBV (ab_EBV) infection and the risk of lymphoma in a multicentric case-control study. Serum samples were collected at study entry from 1,085 incident lymphoma cases from Spain, France, Germany, Czech Republic, Italy and 1,153 age, sex and country matched controls. EBV immunoglobulin G (IgG) serostatus was evaluated through a peptide-based ELISA combining immunodominant epitopes of EBNA1 (BKRF1) and VCA-p18 (BFRF3). Further, immunoblot analysis was performed to evaluate distinct antibody diversity patterns to EBV early antigens (EA), besides EBNA1, VCA-p18, VCA-p40 (BdRF1) and Zebra (BZLF1). Patients with chronic active EBV infection and aberrant EBV activity were characterized as having an abnormal reactive pattern (ab_EBV). Ab EBV was observed in 20.9% of 2,238 included subjects with an increased proportion of cases presenting ab_EBV as compared to the control population (23.9% vs. 18.0% p = 0.001). Ab_EBV positivity was a risk factor for all lymphomas combined (odds ratio [OR] = 1.42, 95% confidence interval [CI]=1.15-1.74), and specifically for chronic lymphocytic leukaemia (OR = 2.96, 95%CI = 2.22-3.95). Lower levels of ab EBV were observed for follicular lymphoma (OR = 0.38, 95%-CI = 0.15-0.98). EBV may be involved in a larger subset of lymphomas among clinically immunocompetent subjects than previously thought, probably explained by an underlying loss of immune control of EBV latent infection. Ab_EBV is a useful too] to explore EBV imbalances preceeding or paralleling possible EBV associated oncogenic events. (C) 2007 Wiley-Liss, Inc.