Epstein-Barr virus (EBV) infection has long been associated with the development of multiple sclerosis (MS). Patients with MS have elevated titres of EBV-specific antibodies in serum and show signs of CNS damage only after EBV infection. Regarding CD8+ T cells, an elevated but ineffective response to EBV was suggested in MS patients, who present with a broader MHC-I-restricted EBV-specific T-cell receptor beta chain (TRB) repertoire compared to controls. It is not known whether this altered EBV response could be subject to dynamic changes, e.g. by approved MS therapies, and whether it is specific for MS. Peripheral blood TRB repertoire samples (n = 1317) of healthy donors (n = 409), patients with MS (n = 710) before and after treatment, patients with neuromyelitis optica spectrum disorder (n = 87), MOG antibody-associated disease (MOGAD) (n = 64) and Susac’s syndrome (n = 47) were analysed. Apart from MS, none of the evaluated diseases presented with a broader anti-EBV TRB repertoire. In MS patients undergoing autologous haematopoietic stem-cell transplantation, EBV reactivation coincided with elevated MHC-I-restricted EBV-specific TRB sequence matches. Therapy with ocrelizumab, teriflunomide or dimethyl fumarate reduced EBV-specific, but not CMV-specific MHC-I-restricted TRB sequence matches. Together, these data suggest that the aberrant MHC-I-restricted T-cell response directed against EBV is specific to MS with regard to neuromyelitis optica, MOGAD and Susac’s syndrome and that it is specifically modified by MS treatments interfering with EBV host cells or activated lymphocytes.

中文翻译：

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多发性硬化症中更广泛的抗 EBV TCR 库：疾病特异性和治疗调节


长期以来，EB 病毒 （EBV） 感染与多发性硬化症 （MS） 的发生有关。MS 患者血清中 EBV 特异性抗体滴度升高，仅在 EBV 感染后才表现出 CNS 损伤的迹象。关于 CD8+ T 细胞，MS 患者对 EBV 的反应升高但无效，与对照组相比，他们表现出更广泛的 MHC-I 限制性 EBV 特异性 T 细胞受体 β 链 （TRB） 库。目前尚不清楚这种改变的 EBV 反应是否会受到动态变化的影响，例如通过批准的 MS 疗法，以及它是否对 MS 具有特异性。健康供体 （n = 409）、治疗前后 MS 患者 （n = 710）、视神经脊髓炎谱系疾病患者 （n = 87） 的外周血 TRB 样本 （n = 1317）、 分析 MOG 抗体相关疾病 （MOGAD） （n = 64） 和 Susac 综合征 （n = 47）。除 MS 外，所有评估的疾病均未出现更广泛的抗 EBV TRB 库。在接受自体造血干细胞移植的 MS 患者中，EBV 再激活与 MHC-I 限制性 EBV 特异性 TRB 序列匹配升高相吻合。奥瑞珠单抗、特立氟胺或富马酸二甲酯治疗可降低 EBV 特异性，但不降低 CMV 特异性 MHC-I 限制性 TRB 序列匹配。总之，这些数据表明，针对 EBV 的异常 MHC-I 限制性 T 细胞反应是 MS 在视神经脊髓炎、MOGAD 和 Susac 综合征方面所特有的，并且它扰 EBV 宿主细胞或活化淋巴细胞的 MS 治疗特异性改变。