Progressive multifocal leukoencephalopathy: an unexpected complication of modern therapeutic monoclonal antibody therapies.
Progressive multifocal leukoencephalopathy: an unexpected complication of modern therapeutic monoclonal antibody therapies.
复制标题
进行性多灶性白质脑病：现代治疗性单克隆抗体疗法的意外并发症。
DOI：
10.1111/j.1469-0691.2011.03653.x
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Khalili,K
中科院分区：
文献类型：
--
作者：
Tavazzi,E;Ferrante,P;Khalili,K
进行性多灶性白质脑病（PML）是一种罕见的中枢神经系统脱髓鞘疾病，由普遍存在的JC病毒重新激活引起。PML通常发生在严重的免疫抑制期间，最常见的原因是人类免疫缺陷病毒感染，淋巴组织增生性疾病和其他形式的癌症。近年来，单克隆抗体（如那他珠单抗、利妥昔单抗、依法利珠单抗）用于治疗几种免疫障碍疾病，如多发性硬化症、类风湿性关节炎、银屑病和系统性红斑狼疮，导致PML的发病率增加。这种现象已经产生了严重的后果，例如导致依法利珠单抗退出市场，以及对其他化合物的使用的重要限制，所有这些化合物的特征都是在改善预后和生活质量方面的高功效。本文就PML的临床、实验室及影像学表现作一综述。此外，提出的致病机制，促进重新激活JC病毒的治疗与单克隆抗体的背景下将被描述。
Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disorder of the central nervous system, caused by the reactivation of the ubiquitous JC virus. PML usually occurs during severe immunosuppression, and the most common causes are represented by human immunodeficiency virus infection, lymphoproliferative disorders and other forms of cancer. Recently, the introduction of monoclonal antibodies (e.g. natalizumab, rituximab, efalizumab) in the treatment of several dysimmune diseases such as multiple sclerosis, rheumatoid arthritis, psoriasis and systemic lupus erythematosus, has led to an increased incidence of PML. This phenomenon has had severe consequences, leading, for example, to the withdrawal from the market of Efalizumab, and important restrictions in the use of the other compounds, all of which are characterized by high efficacy in improving prognosis and quality of life. In this review we will discuss clinical, laboratory and imaging findings of PML. In addition, proposed pathogenetic mechanisms promoting the reactivation of JC virus in the context of treatment with monoclonal antibodies will be described.