The Association between the Comprehensive Epstein-Barr Virus Serologic Profile and Endemic Burkitt Lymphoma
The Association between the Comprehensive Epstein-Barr Virus Serologic Profile and Endemic Burkitt Lymphoma
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DOI：
10.1158/1055-9965.epi-19-0551
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发表时间：
2020-01-01
影响因子：
3.8
通讯作者：
Mbulaiteye, Sam M.
中科院分区：
文献类型：
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作者：
Coghill, Anna E.;Proietti, Carla;Mbulaiteye, Sam M.
背景：在Burkitt淋巴瘤肿瘤中发现Epstein-Barr病毒(EBV)代表了病毒与人类癌症之间的第一个联系，但该病毒在地方性Burkitt淋巴瘤中的潜在作用尚不清楚。在Burkitt淋巴瘤流行地区，几乎所有的儿童都是EBV血清阳性，但只有一小部分儿童患上了疾病。EBV导向免疫的变化可能是一个解释因素。方法：我们使用蛋白质芯片检测了150例Burkitt淋巴瘤患者和150例对照的血清，该芯片针对整个EBV蛋白质组中的202个序列检测了IgG和IgA抗体。使用非配对t检验评估Burkitt淋巴瘤患者和对照之间EBV导向抗体谱系的差异。结果：Burkitt淋巴瘤患者中33例抗EBVIg G抗体阳性(BMRF1、BBLF1、BHRF1、BZLF1、BILF2、BLRF3、BCAp18)均高于对照组(P=4)。疟疾暴露的调整和镰状细胞变异的遗传没有改变相关性。结论：我们的数据表明Burkitt淋巴瘤患者的抗EBV血清学特征发生了变化，相对于未患疾病的儿童，33例检测到的抗EBV抗体显著升高。影响：Burkitt淋巴瘤的特异性特征包括与病毒复制和抗凋亡活性相关的EBV标志物，为未来Burkitt淋巴瘤的发病机制研究提供线索。
Background: The discovery of Epstein-Barr virus (EBV) in Burkitt lymphoma tumors represented the first link between a virus and cancer in humans, but the underlying role of this virus in endemic Burkitt lymphoma remains unclear. Nearly all children in Burkitt lymphoma-endemic areas are seropositive for EBV, but only a small percentage develop disease. Variation in EBV-directed immunity could be an explanatory cofactor.Methods: We examined serum from 150 Burkitt lymphoma cases and 150 controls using a protein microarray that measured IgG and IgA anti-bodies against 202 sequences across the entire EBV proteome. Variation in the EBV-directed antibody repertoire between Burkitt lymphoma cases and controls was assessed using unpaired t tests. ORs quantifying the association between anti-EBV IgG response tertiles and Burkitt lymphoma status were adjusted for age, sex, and study year.Results: Thirty-three anti-EBV IgG responses were elevated in Burkitt lymphoma cases compared with controls (P = 4 for BMRF1 (early antigen), BBLF1 (tegument protein), BHRF1 (Bcl-2 homolog), BZLF1 (Zebra), BILF2 (glycoprotein), BLRF2 [viral capsid antigen (VCA)p23], BDLF4, and BFRF3 (VCAp18). Adjustment for malaria exposure and inheritance of the sickle cell variant did not alter associations.Conclusions: Our data suggest that the anti-EBV serologic profile in patients with Burkitt lymphoma is altered, with strong elevations in 33 of the measured anti-EBV IgG antibodies relative to disease-free children.Impact: The Burkitt lymphoma-specific signature included EBV-based markers relevant for viral replication and antiapoptotic activity, providing clues for future Burkitt lymphoma pathogenesis research.