Miskin Dhanashri P, Koralnik Igor J
Division of Neuroimmunology and Center for Virology and Vaccine Research, Department of Neurology and Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Curr Opin Neurol. 2015 Jun;28(3):288-94. doi: 10.1097/WCO.0000000000000201.
The availability of a growing number of immunomodulatory medications over the past few years has been associated with various JC virus (JCV)-associated brain syndromes in patients with autoimmune diseases, including multiple sclerosis, Crohn's disease, and psoriasis that had not been previously recognized as predisposing factors for progressive multifocal leukoencephalopathy. This review covers the three novel syndromes discovered in the last decade that are caused by JCV infection of neurons and meningeal cells.
For more than 30 years, JCV was thought to exclusively infect oligodendrocytes and astrocytes in the white matter of the brain of immunosuppressed individuals. We now recognize that JCV-infected glial cells are frequently located at the gray-white matter junction or exclusively within the gray matter causing demyelination in the cortex. Mutations in JCV can trigger a change in tropism leading to involvement of other cell types, such as neurons and meningeal cells, causing clinically distinct entities. These new features of JCV infection provide challenges for clinicians taking care of affected patients and investigators studying the biology of this polyomavirus, its pathogenesis, and tropism.
We hope that increasing awareness of these syndromes will lead to early diagnosis, and pave the way for new avenues of research to better understand all aspects of JCV pathogenesis and develop efficient therapies for our patients. However, we need to remain vigilant and open to the possibility that additional JC variants or yet unknown polyomaviruses may also be associated with neurological diseases.
在过去几年中,越来越多的免疫调节药物的出现与自身免疫性疾病患者的各种JC病毒(JCV)相关脑综合征有关,这些疾病包括多发性硬化症、克罗恩病和银屑病,而这些疾病以前并未被认为是进行性多灶性白质脑病的易感因素。本综述涵盖了过去十年中发现的由JCV感染神经元和脑膜细胞引起的三种新型综合征。
30多年来,JCV被认为仅感染免疫抑制个体脑白质中的少突胶质细胞和星形胶质细胞。我们现在认识到,JCV感染的神经胶质细胞经常位于灰白质交界处或仅位于灰质内,导致皮质脱髓鞘。JCV的突变可引发嗜性改变,导致其他细胞类型(如神经元和脑膜细胞)受累,从而引起临床上不同的病症。JCV感染的这些新特征给照顾受影响患者的临床医生以及研究这种多瘤病毒生物学、其发病机制和嗜性的研究人员带来了挑战。
我们希望提高对这些综合征的认识将有助于早期诊断,并为新的研究途径铺平道路,以便更好地理解JCV发病机制的各个方面,并为我们的患者开发有效的治疗方法。然而,我们需要保持警惕,并对其他JCV变体或尚未知晓的多瘤病毒也可能与神经系统疾病相关的可能性持开放态度。