High Levels of Antibody that Neutralize B-cell Infection of Epstein-Barr Virus and that Bind EBV gp350 Are Associated with a Lower Risk of Nasopharyngeal Carcinoma.
High Levels of Antibody that Neutralize B-cell Infection of Epstein-Barr Virus and that Bind EBV gp350 Are Associated with a Lower Risk of Nasopharyngeal Carcinoma.
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DOI：
10.1158/1078-0432.ccr-15-2299
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发表时间：
2016-07-15
期刊：
影响因子：
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通讯作者：
Cohen JI
中科院分区：
文献类型：
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作者：
Coghill AE;Bu W;Nguyen H;Hsu WL;Yu KJ;Lou PJ;Wang CP;Chen CJ;Hildesheim A;Cohen JI
伊加抗体升高表明持续暴露于巴尔病毒（EBV）是鼻咽癌（NPC）的高风险生物标志物，NPC是一种EBV相关的上皮肿瘤。然而，限制暴露于病毒的保护性生物标志物尚未确定。我们评估了通过靶向参与病毒细胞进入的糖蛋白（包括EBV疫苗候选糖蛋白350）来中和EBV感染的抗体是否与降低NPC风险相关。在台湾358个高风险NPC多发性家庭的2，557名个体的前瞻性队列中，我们确定了21例NPC病例和50例无疾病对照。为了补充来自高风险家庭的数据，我们进一步从台湾普通人群中确定了30例流行的NPC病例和50例健康对照。我们定量了EBV中和抗体、针对参与B细胞和上皮细胞进入的EBV糖蛋白的抗体以及抗EBNA 1伊加（一种高危NPC生物标志物）。无病对照组中阻断B细胞感染的EBV中和抗体和抗EBVgp 350抗体的水平显著高于NPC病例组（P<0.03）。同时具有低EBV中和能力和高EBNA 1伊加的家族成员患NPC的风险增加7倍（95%CI=1.9-28.7）。上皮细胞感染的中和抗体在发病病例和无病对照组之间没有差异。诊断时（鼻咽癌流行期）抗糖蛋白抗体水平明显高于诊断前（P<0.01）。EB病毒中和抗体和抗gp 350抗体滴度升高是鼻咽癌的低风险生物标志物。这些数据表明，诱导有效的EBV gp 350和B细胞中和抗体的疫苗可以降低EBV相关癌症（如NPC）的风险。
Elevated IgA antibodies indicative of ongoing exposure to Epstein Barr virus (EBV) are high-risk biomarkers for nasopharyngeal carcinoma (NPC), an EBV-related epithelial tumor. However, protective biomarkers that limit exposure to the virus have not been defined. We evaluated whether antibodies that can neutralize EBV infection by targeting glycoproteins involved in viral cell entry, including EBV vaccine candidate glycoprotein350, were associated with lower NPC risk. In a prospective cohort of 2,557 individuals from 358 high-risk NPC multiplex families in Taiwan, we identified 21 incident NPC cases and 50 disease-free controls. To complement data from high-risk families, we further identified 30 prevalent NPC cases and 50 healthy controls from the general Taiwanese population. We quantified EBV neutralizing antibody, antibodies against EBV glycoproteins involved in B-cell and epithelial cell entry, and anti-EBNA1 IgA, a high-risk NPC biomarker. EBV neutralizing antibodies blocking B-cell infection and anti-EBVgp350 antibodies were present at significantly higher levels in disease-free controls compared to incident NPC cases (P<0.03). Family members with both low EBV neutralizing potential and elevated EBNA1 IgA had a 7-fold increased risk of NPC (95%CI=1.9–28.7). Neutralizing antibodies against epithelial cell infection did not differ between incident cases and disease-free controls. Anti-glycoprotein antibody levels measured at diagnosis (prevalent NPC) were significantly higher than levels measured prior to diagnosis (P<0.01). Elevated titers of EBV neutralizing antibody and anti-gp350 antibody were low-risk biomarkers for NPC. These data suggest that a vaccine that induces potent EBV gp350 and B-cell neutralizing antibodies could reduce the risk of EBV-related cancers such as NPC.