多发性硬化患者抗EB病毒抗体阳性检出率的Meta分析

Meta analysis on the positive detection rate of anti-epstein-barr virus antibodies in population with multiple sclerosis

目的 通过Meta分析探讨多发性硬化(MS)患者体内抗EB病毒(EBV)抗体阳性率。方法 检索对MS病例与对照血清中抗EBV抗体进行检测的随机对照试验(RCT),并通过Meta分析探索各种抗EBV抗体与MS之间的关系。计算机检索中国期刊全文数据库(CNKI)、万方科技期刊全文数据库、PubMed、EMbase和维普中文科技期刊全文数据库(VIP),检索时限均从建库至2021年12月。两名研究者严格根据制定的纳入及排除标准独立进行文献筛选并提取基本资料,依据修改后的纽卡斯尔-渥太华量表(NOS)工具评价文献质量。采用Rev Man 5.3软件合并计算所有纳入文献中的每一种抗EBV抗体血清阳性率的OR,并进行敏感性分析和亚组分析。以Egger检验评价发表偏倚。结果 共纳入35项研究。MS患者EBV衣壳抗原抗体(EBV-VCA)IgG/IgM、EBV核心抗原抗体(EBNA)IgG血清阳性率明显高于对照者,效应量指标总体OR值及其95%CI分别为:EBV-VCA IgM(OR=3.44,95%CI:1.93~6.13)、EBV-VCA IgG(OR=4.79,95%CI:2.82~8.15)、EBNA IgG(OR=4.45,95%CI:2.87~6.89),差异均有统计学意义(均P<0.05)。MS患者与对照者EBV早期抗原抗体(EBEA)IgG血清阳性率差异无统计学意义(OR=1.33,95%CI:0.94~1.88),合并效应量检验结果(Z=1.6,P=0.11)。采用亚组分析寻找各研究间异质性的来源。Egger检验显示存在发表偏倚。结论 本研究从血清学方向为EBV感染与MS之间的相关性提供了证据支持。MS患者EBV-VCA IgG/IgM和EBNA IgG这3种抗体血清阳性率均明显高于对照者,提示EBV感染是MS致病的重要危险因素。

Objective To investigate the prevalence of anti-Epstein-Barr virus(anti-EBV) antibodies in population with multiple sclerosis(MS).Methods Search the randomized controlled trials(RCT) studies which examined the anti-EBV antibodies in the serum of MS cases and controls, and conducted a meta-analysis to explore the relationship between various anti-EBV antibodies and the MS. The databases, including China Network Knowledge Infrastructure(CNKI), WANFANG Database, PubMed, EMbase, and Chinese Weipu Database(VIP), were searched from inception to December 2021. Two reviewers independently screened the articles and extracted basic data in strict accordance with the inclusion and exclusion criteria. Quality assessment was performed using a modified version of the Newcastle-Ottawa assessment scale(NOS). The data synthesis, sensitivity analyses, and subgroup analyses were measured with Review Manager(Rev Man version 5.3) software, and also the OR of seropositivity to EBV were calculated for each of the anti-EBV antibodies. Egger test was used to evaluate the publication bias.Results A total of 35 studies were included. There was a statistically significant higher seroprevalence of anti-EBV viral capsid antigen(EBV-VCA) IgG/IgM and anti-EBV nuclear antigen(EBNA) IgG in patients with MS compared to controls. The overall OR value of the effect quantity index for anti-VCA IgM was 3.44(95%CI:1.93-6.13), that for anti-VCA IgG was 4.79(95%CI:2.82-8.15), and that for anti-EBNA IgG was 4.45(95%CI:2.87-6.89). The differences were statistically significant(all P<0.05). The overall OR value for anti-EBV early antigen(EBEA) IgG was 1.33(95%CI:0.94-1.88) with the test statistic(Z=1.6, P=0.11) indicating that the difference in seropositivity rates between MS and control groups was not significant. Subgroup analysis were performed to explore the potential sources of heterogeneity. The Egger test showed that there was significant publication bias.Conclusions The findings from this study provide strong serological evidence for the association between EBV infection and MS. The prevalence of anti-VCA IgG/IgM antibody and anti-EBNA IgG antibody in MS patients are significantly higher than those in controls, which added the evidence of EBV infection as an important risk factor for MS development.