From the Department of Neurology (F.P., C.O., P.S., M.N., K.R.), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin; Institute for Experimental Immunology (D.W., T.L., K.S., E.G.-G.), affiliated with EUROIMMUN Medizinische Labordiagnostika AG, Luebeck; and Molecular Neuroimmunology Group (B.W., S.J.), Department of Neurology, University of Heidelberg, Germany.
Neurol Neuroimmunol Neuroinflamm. 2025 Jan;12(1):e200332. doi: 10.1212/NXI.0000000000200332. Epub 2024 Nov 27.
There is a strong link between Epstein-Barr virus (EBV) and multiple sclerosis (MS), but the underlying mechanisms are unclear. Patients with MS typically have a polyspecific intrathecal production of immunoglobulin G (IgG), part of which is directed against various microbial antigens. In this study, we comprehensively analyzed seroprevalences and frequencies of an intrathecal IgG production to EBV compared with 10 other common microbes in patients with MS.
Antibodies to EBV and to , cytomegalovirus, herpes simplex virus type 1/2, measles virus, mumps virus, rubella virus, parvovirus B19, tick-borne encephalitis virus, , and varicella zoster virus (VZV) were determined in stored paired CSF and serum samples of 50 patients with MS. Intrathecal antimicrobial antibody production was assessed by calculating antibody indices (AIs) according to standard formula.
While 50 (100%) of 50 patients with MS were EBV seropositive, seroprevalences of all other 10 microbes were lower, ranging from 94% (VZV) to 6% (). An intrathecal production of antimicrobial antibodies was detected in 102 (28%) of 370 AI determinations of patients who were seropositive to the respective antimicrobial antibodies but was practically absent in seronegative patients (2/187 [1%], < 0.0001). The frequency of intrathecally produced antimicrobial antibodies among patients who were seropositive for the respective antibodies was roughly 40% for measles, rubella, mumps, and VZV and 70% for parvovirus B19. By contrast, the frequency of intrathecally produced EBV antibodies was low (10%) and, when related to their respective seroprevalences, lower than those of all other investigated microbes.
Despite the universal EBV seroprevalence, the frequency of intrathecally produced EBV antibodies in patients with MS is lower than that of other microbes, whose seroprevalences are lower than those of EBV. This seemingly paradoxical finding underscores the unique role of EBV in MS and could be explained by the hypothesis that B lineage cells responsible for intrathecal antibody production are primed during and through acute EBV infection to enter the CNS of patients with MS, that is, at a time point when EBV antibody-producing cells have not yet been generated and, therefore, are not yet available for entering the CNS.
爱泼斯坦-巴尔病毒（EBV）与多发性硬化症（MS）之间存在很强的关联，但潜在机制尚不清楚。MS 患者通常会在鞘内产生多特异性免疫球蛋白 G（IgG），其中一部分针对各种微生物抗原。在这项研究中，我们全面分析了 EBV 与其他 10 种常见微生物相比，在 MS 患者中的血清流行率和鞘内 IgG 产生频率。
在 50 例 MS 患者的储存配对 CSF 和血清样本中，测定了 EBV 以及巨细胞病毒、单纯疱疹病毒 1/2 型、麻疹病毒、腮腺炎病毒、风疹病毒、细小病毒 B19、蜱传脑炎病毒、乙型肝炎病毒和水痘带状疱疹病毒（VZV）的抗体。根据标准公式计算抗体指数（AI）来评估鞘内抗菌抗体的产生。
50 例 MS 患者均为 EBV 血清阳性（100%），而其他 10 种微生物的血清流行率较低，范围从 94%（VZV）到 6%（乙型肝炎病毒）。在对各自抗菌抗体血清阳性的 370 例 AI 测定中，有 102 例（28%）检测到抗菌抗体鞘内产生，但在血清阴性患者中几乎不存在（2/187 [1%]，<0.0001）。在对各自抗体血清阳性的患者中，麻疹、风疹、腮腺炎和 VZV 的抗菌抗体鞘内产生频率约为 40%，细小病毒 B19 为 70%。相比之下，EBV 抗体的鞘内产生频率较低（10%），与其各自的血清流行率相比，低于所有其他研究的微生物。
尽管 EBV 的血清流行率普遍存在，但 MS 患者中 EBV 鞘内产生抗体的频率低于其他微生物，而这些微生物的血清流行率低于 EBV。这种看似矛盾的发现突显了 EBV 在 MS 中的独特作用，这可以用以下假设来解释：负责鞘内抗体产生的 B 细胞系在 EBV 感染期间和之后被激活，进入 MS 患者的中枢神经系统，即在 EBV 抗体产生细胞尚未产生并且尚未用于进入中枢神经系统的时间点。
