Bose Abigail, Khalighinejad Farnaz, Hoaglin David C, Hemond Christopher C
University of Massachusetts Chan Medical School.
University of Massachusetts Chan Medical School; Nuvance Health Medical Center.
Mult Scler Relat Disord. 2024 Apr;84:105410. doi: 10.1016/j.msard.2023.105410. Epub 2023 Dec 30.
EBV is a necessary but not sufficient factor in the pathophysiology of multiple sclerosis (MS). EBV antibodies to the nuclear antigen (EBNA1) and viral capsid antigen (VCA) rise rapidly prior to MS disease manifestations, and their absence has clinical utility with a high negative predictive value. It remains unclear whether EBV levels act as prognostic, monitoring, or pharmacodynamic/response biomarkers. Substantial literature on this topic exists but has not been systematically reviewed. We hypothesized that EBV levels against EBNA1 and VCA are potential prognostic and monitoring biomarkers in MS, and that patient population, MS clinical phenotype, and EBV assay method may play important roles in explaining variation among study outcomes.
We systematically searched PubMed and EMBASE from inception to April 1, 2022. After removal of duplicates, records were screened by abstract. Remaining full-text articles were reviewed. Clinical and MRI data were extracted from full-text articles for comparison and synthesis.
Searches yielded 696 unique results; 285 were reviewed in full, and 36 met criteria for data extraction. Heterogeneity in sample population, clinical outcome measures, assay methods and statistical analyses precluded a meta-analysis. EBV levels were not consistently associated with clinical disease markers including conversion from CIS to RRMS, neurological disability, or disease phenotype. Studies using repeated-measures design suggest that EBNA1 levels may temporarily reflect inflammatory disease activity as assessed by gadolinium-enhancing Magnetic Resonance Imaging (MRI) lesions. Limited data also suggest a decrease in EBV levels following initiation of certain disease-modifying therapies.
Heterogeneous methodology limited generalization and meta-analysis. EBV antibody levels are unlikely to represent prognostic biomarkers in MS. The areas of highest ongoing promise relate to diagnostic exclusion and pharmacodynamic/disease response. Use of EBV antibodies as biomarkers in clinical practice remains additionally limited by lack of methodological precision, reliability, and validation.
EB病毒是多发性硬化症（MS）病理生理学中的一个必要但不充分的因素。在MS疾病表现出现之前，针对核抗原（EBNA1）和病毒衣壳抗原（VCA）的EB病毒抗体迅速升高，而它们的缺乏具有临床实用性，阴性预测价值高。目前尚不清楚EB病毒水平是否可作为预后、监测或药效学/反应生物标志物。关于这一主题有大量文献，但尚未进行系统综述。我们假设针对EBNA1和VCA的EB病毒水平是MS潜在的预后和监测生物标志物，并且患者群体、MS临床表型和EB病毒检测方法可能在解释研究结果的差异方面发挥重要作用。
我们系统检索了从创刊到2022年4月1日的PubMed和EMBASE。去除重复记录后，通过摘要筛选记录。对剩余的全文文章进行评审。从全文文章中提取临床和MRI数据进行比较和综合。
检索产生了696个独特结果；对285篇进行了全文评审，36篇符合数据提取标准。样本群体、临床结局指标、检测方法和统计分析的异质性排除了进行荟萃分析的可能。EB病毒水平与包括从临床孤立综合征（CIS）转变为复发缓解型多发性硬化症（RRMS）、神经功能残疾或疾病表型在内的临床疾病标志物并无一致关联。采用重复测量设计的研究表明，EBNA1水平可能会暂时反映钆增强磁共振成像（MRI）病变所评估的炎症性疾病活动。有限的数据还表明，在开始某些疾病修正治疗后，EB病毒水平会下降。
方法的异质性限制了推广和荟萃分析。EB病毒抗体水平不太可能代表MS的预后生物标志物。目前最有前景的领域与诊断排除以及药效学/疾病反应有关。EB病毒抗体作为生物标志物在临床实践中的应用还因缺乏方法的精确性、可靠性和验证而受到进一步限制。
