Modern drugs in use for multiple sclerosis patients have shown immense beneficial effects on relapse rate, disease progression and MRI-activity. However, recent increase of progressive multifocal leukoencephalopathy related with some of them is not unders

近年来，对多发性硬化症(MS)相关病理机制的了解取得了进展，导致了高度特异的治疗方法的发展。然而，这些疗法中的一些已经导致了严重的脑部病毒学感染，例如进行性多灶性白质脑病(PML)。在其他免疫功能正常的MS(但也包括牛皮癣和关节炎)患者中，PML(一种机会性JC病毒介导的、通常是致命的中枢神经系统感染)在单抗(如Natalizumab、rituximab和efalizumab)下的发生和关键病理机制仍不清楚。到目前为止，PML通常与免疫功能严重受损的患者有关，例如艾滋病毒或白血病疾病。在一项初步研究中，我们通过量化免疫效应细胞对刺激的反应作为细胞免疫的功能参数，建立了一种灵敏的免疫分析方法，该方法适用于500多名接受各种治疗的MS患者以及最近20例单抗和HIV相关的PML患者。为了获得更高的特异性，并关于PML的发病机制，以确定可能的宿主易感性，牛津大学Fuggers教授团队计划针对导致MS患者意外发生PML的免疫遗传学(HLA型PML患者)和免疫学(CD4+/CD8+细胞对免疫优势JCV表位(S)抗原特异性刺激的能力)因素进行研究。根据这项研究的结果，我们期待着对中枢神经系统JC病毒感染的更好了解，这将有助于开发一种预测标记物来识别PML的风险患者。

Recent progress in the understanding of relevant pathomechanisms of multiple sclerosis (MS) has led to the development of highly specific therapeutic approaches. However, some of these therapeutics have led to severe virologic infections of the brain, e.g. progressive multifocal leukoencephalopathy (PML). The occurrence and key pathomechanisms of PML - an opportunistic JC viral mediated and typically fatal CNS-infection - under monoclonal antiibodies (mAb), e.g. natalizumab, rituximab and efalizumab in otherwise immunocompetent MS (but also psoriasis- and arthritis-) patients remain cryptic. So far, PML was typically associated with severely immunocompromised patients, e.g. HIV or leukemic diseases. In a pilot study, we have established a sensitive immunoassay by quantifying cellular energetics of immune effector cells in response to stimulation as a functional parameter of cellular immunity in over 500 MS patients under various therapies and in 20 recent cases of mAb- and HIV-related PML. To achieve a higher degree of specificity, and concerning the pathogenesis of PML, to identify possible host predisposition, the project as planned in Prof. Fuggers group at the University of Oxford is aiming at immunogenetic (HLA type of PML patients) and immunologic (ability of CD4+/CD8+-cells to response to antigen specific stimulation by the immunodominant JCV epitope(s)) factors leading to the unexpected occurrence of PML in MS patients. By results gained from this study, we await a better understanding of JC viral infection of the CNS which will enable the development of a predictive marker identifying patients at risk for PML.