Moreno Monica A, Or-Geva Noga, Aftab Blake T, Khanna Rajiv, Croze Ed, Steinman Lawrence, Han May H
Department of Neurology and Neurological Sciences (M.A.M., N.O., L.S., M.H.H.), Stanford University School of Medicine, Multiple Sclerosis Center; Interdepartmental Program in Immunology (M.A.M., N.O., L.S., M.H.H.), Stanford; Atara Biotherapeutics (B.T.A., E.C.), San Francisco, CA; and Queensland Institute of Medical Research (R.K.), Brisbane, Queensland, Australia.
Neurol Neuroimmunol Neuroinflamm. 2018 Jun 7;5(4):e466. doi: 10.1212/NXI.0000000000000466. eCollection 2018 Jul.
We sought to confirm the presence and frequency of B cells and Epstein-Barr virus (EBV) (latent and lytic phase) antigens in archived MS and non-MS brain tissue by immunohistochemistry.
We quantified the type and location of B-cell subsets within active and chronic MS brain lesions in relation to viral antigen expression. The presence of EBV-infected cells was further confirmed by in situ hybridization to detect the EBV RNA transcript, EBV-encoded RNA-1 (EBER-1).
We report the presence of EBV latent membrane protein 1 (LMP-1) in 93% of MS and 78% of control brains, with a greater percentage of MS brains containing CD138 plasma cells and LMP-1-rich populations. Notably, 78% of chronic MS lesions and 33.3% of non-MS brains contained parenchymal CD138 plasma cells. EBV early lytic protein, EBV immediate-early lytic gene (BZLF1), was also observed in 46% of MS, primarily in association with chronic lesions and 44% of non-MS brain tissue. Furthermore, 85% of MS brains revealed frequent EBER-positive cells, whereas non-MS brains seldom contained EBER-positive cells. EBV infection was detectable, by immunohistochemistry and by in situ hybridization, in both MS and non-MS brains, although latent virus was more prevalent in MS brains, while lytic virus was restricted to chronic MS lesions.
Together, our observations suggest an uncharacterized link between the EBV virus life cycle and MS pathogenesis.
我们试图通过免疫组织化学方法，证实存档的多发性硬化症（MS）和非MS脑组织中B细胞及爱泼斯坦-巴尔病毒（EBV）（潜伏和裂解期）抗原的存在及其频率。
我们对活动期和慢性期MS脑损伤内B细胞亚群的类型和位置与病毒抗原表达的关系进行了量化。通过原位杂交检测EBV RNA转录本EBV编码RNA-1（EBER-1），进一步证实EBV感染细胞的存在。
我们报告在93%的MS脑和78%的对照脑中存在EBV潜伏膜蛋白1（LMP-1），含有CD138浆细胞和富含LMP-1群体的MS脑比例更高。值得注意的是，78%的慢性MS损伤和33.3%的非MS脑含有实质CD138浆细胞。在46%的MS脑中也观察到EBV早期裂解蛋白、EBV立即早期裂解基因（BZLF1），主要与慢性损伤相关，在44%的非MS脑组织中也有观察到。此外，85%的MS脑显示频繁的EBER阳性细胞，而非MS脑很少含有EBER阳性细胞。通过免疫组织化学和原位杂交在MS和非MS脑中均检测到EBV感染，尽管潜伏病毒在MS脑中更普遍，而裂解病毒仅限于慢性MS损伤。
总之，我们的观察结果提示EBV病毒生命周期与MS发病机制之间存在一种未明确的联系。
