Progressive multifocal leukoencephalopathy: lessons from AIDS and natalizumab
Progressive multifocal leukoencephalopathy: lessons from AIDS and natalizumab
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DOI：
10.1179/016164106x98198
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发表时间：
2006-04-01
影响因子：
1.9
通讯作者：
Houff, S
中科院分区：
文献类型：
--
作者：
Berger, JR;Houff, S
由于艾滋病大流行导致的进行性多灶性白质脑病（PML）的发病率急剧增加，以及最近PML与那他珠单抗（一种阻断炎性细胞进入大脑的α 4整合素单克隆抗体）给药的相关性，激发了人们对这种以前不清楚的病毒性脱髓鞘疾病的极大兴趣。这种疾病的病因是JC病毒（JCV），一种多瘤病毒，在全世界80%的人群中观察到。血清流行病学研究表明，这种病毒的感染通常发生在20岁之前。没有发现由JCV感染引起的原发疾病，人与人之间的传播方式仍然不清楚。感染后，病毒潜伏在骨髓、脾脏、扁桃体和其他组织中。病毒周期性地重新激活，在此期间可以在循环外周淋巴细胞中证实。后者在免疫抑制人群中比在正常受试者中更常见。尽管有大量的人感染JCV，PML仍然是一种相对罕见的疾病。在没有潜在诱发疾病的情况下很少观察到，通常是导致细胞免疫受损的疾病。多种因素可能导致HIV感染者PML相对于其他潜在免疫抑制疾病的频率独特增加。初步数据表明，与其他感染性并发症相比，那他珠单抗似乎明显易使接受者发生PML。对这些人群的研究对于了解疾病发病机制将是非常宝贵的。
The dramatic increase in the incidence of progressive multifocal leukoencephalopathy (PML) that occurred as a consequence of the AIDS pandemic and the recent association of PML with the administration of natalizumab, a monoclonal antibody to alpha 4 integrin that blocks inflammatory cell entry into the brain, has stimulated a great deal of interest in this previously obscure viral demyelinating disease. The etiology of this disorder is JC virus (JCV), a polyoma virus, observed in 80% of the population worldwide. Seroepidemiological studies indicate that infection with this virus typically occurs before the age of 20 years. No primary illness owing to JCV infection has been recognized and the means of spread from person to person remains obscure. Following infection, the virus becomes latent in bone marrow, spleen, tonsils and other tissues. Periodically the virus reactivates during which time it can be demonstrated in circulating peripheral lymphocytes. The latter is significantly more commonly observed in immunosuppressed populations than that in normal subjects. Despite the large pool of people infected with JCV, PML remains a relatively rare disease. It is seldom observed in the absence of an underlying predisposing illness, typically one that results in impaired cellular immunity. A variety of factors are likely responsible for the unique increase in frequency of PML in HIV infection relative to other underling immunosuppressive disorders. Preliminary data suggests that natalizumab appears to distinctively predispose recipients to PML relative to other infectious complications. Studies in these populations will be invaluable in understanding the mechanisms of disease pathogenesis.