Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Expert Rev Clin Immunol. 2012 Jan;8(1):63-72. doi: 10.1586/eci.11.85.
Natalizumab represents an effective biological therapy to treat relapsing-remitting forms of multiple sclerosis and Crohn's disease by blocking the migration of inflammatory cells to the brain and gut. Natalizumab, however, is associated with a risk of progressive multifocal leukoencephalopathy (PML) caused by the reactivation of JC virus. The emergence of PML in this setting has moved PML from being a rare disease mostly seen in HIV-infected individuals to become an important cause of complications in patients receiving immunomodulatory treatments. The incidence of PML associated with natalizumab treatment is approximately 1.5:750, but this increases to approximately 1:100 in patients after 24-36 doses based on available estimates of individuals who have a prior history of immunosuppressive treatment and are antibody positive to JC virus. Natalizumab treatment has raised questions about the pathogenesis of PML but also has provided the opportunity to investigate sites of virus latency and mechanisms of trafficking to the brain.
那他珠单抗通过阻断炎症细胞向大脑和肠道的迁移，代表了一种有效的生物治疗方法，可用于治疗复发缓解型多发性硬化症和克罗恩病。然而，那他珠单抗与进行性多灶性白质脑病（PML）的风险相关，这种疾病是由 JC 病毒的重新激活引起的。在这种情况下出现 PML，使 PML 从一种主要见于 HIV 感染者的罕见疾病，变成了接受免疫调节治疗的患者的重要并发症原因。与那他珠单抗治疗相关的 PML 的发生率约为 1.5:750，但根据对既往有免疫抑制治疗史且对 JC 病毒抗体阳性的个体的估计，这一比例在接受 24-36 剂治疗的患者中增加至约 1:100。那他珠单抗治疗引发了对 PML 发病机制的质疑，但也为研究病毒潜伏部位和向大脑转移的机制提供了机会。
