Vietzen Hannes, Kühner Laura M, Berger Sarah M, Ponleitner Markus, Graninger Marianne, Pistorius Charlotte, Jungbauer Christof, Reindl Markus, Saucke Henrieke, Kauth Franziska, Wendel Eva-Maria, Rostásy Kevin, Breu Markus, Kornek Barbara, Bsteh Gabriel, Berger Thomas, Rommer Paulus, Puchhammer-Stöckl Elisabeth
Center for Virology, Medical University of Vienna, Vienna, Austria.
Department of Neurology, Medical University of Vienna, Vienna, Austria.
Nat Commun. 2025 Jul 14;16(1):6416. doi: 10.1038/s41467-025-61751-9.
Multiple sclerosis (MS) is an immune-mediated demyelinating disease. Epstein-Barr virus (EBV) encodes for the EBNA-1 region that induces autoreactive antibody responses, which are likely critically involved in MS pathogenesis. Here we investigate whether these EBNA-1-specific antibodies can serve as a biomarker to identify at-risk individuals for MS. We quantify EBNA-1-specific antibody titers from 324 relapsing-remitting MS patients and 324 matched controls in longitudinal follow-up plasma samples, starting from the individual's EBV-seroconversion. In MS patients, significantly elevated EBNA-1-specific IgG titers are identified that are increased already as early as nine months after EBV-seroconversion (OR:5.7; 95% CI: 4.1-8.1; P < 0.0001) and a median 5.4 years prior to MS diagnosis. Especially, the presence of continuously high EBNA-1-specific antibody titers is associated with a more rapid MS diagnosis after EBV-seroconversion (P < 0.0001). Thus, the quantification of EBNA-1-specific IgG antibody levels may provide a prognostic biomarker to determine the individual's risk for the diagnosis of MS.
多发性硬化症（MS）是一种免疫介导的脱髓鞘疾病。爱泼斯坦-巴尔病毒（EBV）编码EBNA-1区域，该区域可诱导自身反应性抗体反应，而这可能在MS发病机制中起关键作用。在此，我们研究这些EBNA-1特异性抗体是否可作为一种生物标志物，用于识别MS的高危个体。我们对324例复发缓解型MS患者和324例匹配对照的纵向随访血浆样本中的EBNA-1特异性抗体滴度进行了量化，样本采集从个体的EBV血清学转换开始。在MS患者中，我们发现EBNA-1特异性IgG滴度显著升高，早在EBV血清学转换后9个月就已升高（比值比：5.7；95%置信区间：4.1 - 8.1；P 0.0001），且在MS诊断前中位数为5.4年。特别是，持续高EBNA-1特异性抗体滴度的存在与EBV血清学转换后更快的MS诊断相关（P < 0.0001）。因此，EBNA-1特异性IgG抗体水平的量化可能提供一种预后生物标志物，以确定个体患MS的风险。
