Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, United States.
Graduate Program in Immunology, Program in Biomedical Sciences, University of Michigan Medical School, Ann Arbor, MI, United States.
Front Immunol. 2018 Feb 2;9:138. doi: 10.3389/fimmu.2018.00138. eCollection 2018.
The increased use of newer potent immunomodulatory therapies for multiple sclerosis (MS), including natalizumab, fingolimod, and dimethyl fumarate, has expanded the patient population at risk for developing progressive multifocal leukoencephalopathy (PML). These MS therapies shift the profile of lymphocytes within the central nervous system (CNS) leading to increased anti-inflammatory subsets and decreased immunosurveillance. Similar to MS, PML is a demyelinating disease of the CNS, but it is caused by the JC virus. The manifestation of PML requires the presence of an active, genetically rearranged form of the JC virus within CNS glial cells, coupled with the loss of appropriate JC virus-specific immune responses. The reliability of metrics used to predict risk for PML could be improved if all three components, i.e., viral genetic strain, localization, and host immune function, were taken into account. Advances in our understanding of the critical lymphocyte subpopulation changes induced by these MS therapies and ability to detect viral mutation and reactivation will facilitate efforts to develop these metrics.
新型强效免疫调节疗法（如那他珠单抗、芬戈莫德和富马酸二甲酯）在多发性硬化症（MS）中的应用日益增多，这扩大了发生进行性多灶性白质脑病（PML）的患者群体。这些 MS 疗法改变了中枢神经系统（CNS）内淋巴细胞的特征，导致抗炎亚群增加和免疫监视减少。与 MS 类似，PML 是一种 CNS 的脱髓鞘疾病，但它是由 JC 病毒引起的。PML 的表现需要 CNS 神经胶质细胞内存在活跃的、基因重排的 JC 病毒，同时伴有适当的 JC 病毒特异性免疫反应丧失。如果考虑到病毒遗传株、定位和宿主免疫功能这三个因素，用于预测 PML 风险的指标的可靠性可能会提高。我们对这些 MS 疗法引起的关键淋巴细胞亚群变化的理解的进步，以及检测病毒突变和再激活的能力，将有助于开发这些指标。
