EB 病毒与多发性硬化症:多发性硬化症患者体内 LMP2A 的表达

S. Agostini, R. Mancuso, Domenico Caputo, M. Rovaris, Mario Clerici
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摘要

一些证据,包括血清中爱泼斯坦-巴氏病毒(EBV)特异性抗体滴度的升高和患者大脑中 EBV DNA 的存在,都表明这种病毒可能在多发性硬化症(MS)的发病机制中起着重要作用。本研究的目的是验证 LMP2A 和 EBNA-1 这两个 EBV 基因的表达在多发性硬化症患者中是否发生了改变。本研究评估了 EBV 血清阳性多发性硬化症患者(57 人,其中 31 人为复发性缓解型多发性硬化症患者,26 人为进行性多发性硬化症患者)和年龄与性别匹配的健康对照组(49 人)血液中的 EBV 病毒载量、LMP2A 和 EBNA-1 基因表达以及 EBNA-1 抗体滴度。结果显示,与健康对照组相比,多发性硬化症患者的 EBNA-1 和 VCA 抗体滴度明显升高(两种抗体的 p < 0.05);与健康对照组相比,多发性硬化症患者的 EBV DNA 检测更为频繁,但未达到统计学意义。在病毒基因表达方面,多发性硬化症患者检测到 LMP2A 的频率和表达量明显高于普通人群(P < 0.005),而 EBNA-1 则无差异。仅就患者而言,与 RRMS 相比,EBNA-1 在 PMS 中的检出率明显更高(p < 0.05),而 LMP2A 则无差异。LMP2A潜伏相关基因在多发性硬化症患者中的表达增加支持了 EBV 在疾病病理中发挥作用的假设。
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EBV and multiple sclerosis: expression of LMP2A in MS patients
Several evidences, including increased serum titers of Epstein–Barr virus (EBV)-specific antibodies and the presence of EBV DNA in brain of patients suggest a possible role of this virus in the pathogenesis of Multiple Sclerosis (MS), a chronic neurodegenerative disease with an unknown etiopathology. Aim of the present study is to verify if the expression of LMP2A and EBNA-1, two EBV genes, is altered in MS patients. EBV viral load, LMP2A and EBNA-1 gene expression and EBNA-1 antibodies titers were evaluated in blood of EBV-seropositive MS patients (n = 57; 31 relapsing remitting –RRMS- and 26 progressive -PMS-patients) and age- and sex-matched healthy controls (HC, n = 49). Results showed that EBNA-1 and VCA antibodies titers are significantly augmented in MS patients compared to HC (p < 0.05 for both antibodies); detection of EBV DNA was more frequent as well in MS patients compared to HC, although without reaching statistical significance. Regarding viral gene expression, LMP2A was significantly more frequently detected and more expressed in MS patients compared to HC (p < 0.005) whereas no differences were observed for EBNA-1. Considering patients alone, EBNA-1 was significantly more frequent in PMS compared to RRMS (p < 0.05), whereas no differences were observed for LMP2A. Increased expression of the LMP2A latency-associated gene in MS patients supports the hypothesis that EBV plays a role in disease etiopathology.
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