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多发性硬化症的疾病修饰药物与 JCV 表达。

Disease-modifying drugs for multiple sclerosis and JC virus expression.

机构信息

College of Dentistry, University of Kentucky, Lexington, KY 40536-0284, USA.

出版信息

J Neurovirol. 2012 Oct;18(5):411-5. doi: 10.1007/s13365-012-0107-0. Epub 2012 May 15.

DOI:10.1007/s13365-012-0107-0
PMID:22585288
Abstract

Natalizumab-associated progressive multifocal leukoencephalopathy in multiple sclerosis (MS) occurred in two individuals also treated with interferon β1a, raising concerns about the interaction of these disease-modifying agents and leading to the recommendation to avoid their concomitant administration. However, type I interferons are antiviral. Using a real-time quantitative polymerase chain reaction for the detection and quantification of the John Cunningham virus (JCV), DNA in peripheral blood mononuclear cells (PBMCs), and urine in MS patients, we tested the hypothesis that MS disease-modifying drugs (DMD) qualitatively and quantitatively alter JCV prevalence and viral copy numbers. Two hundred thirty-nine patients were enrolled in a cross-sectional study in which blood and urine specimens were collected at a single time and 37 newly diagnosed, treatment-naïve MS patients were enrolled in a longitudinal study in which specimens were obtained at diagnosis and 6 months after treatment initiation. JCV DNA was detected in PBMCs of only two patients (0.07 %), but was commonly detected in the urine (46.8 %) in this population. There was no effect of DMDs on blood or urinary JCV prevalence or viral copy numbers with either glatiramer acetate (Copaxone®) or interferon-β therapy (Avonex®, Betaseron®, or Rebif®). The small number of patients on other therapies precluded meaningful comment about their effects. No obvious effect of the platform DMDs on JCV prevalence was observed even for the interferon-βs.

摘要

那他昔单抗相关性进行性多灶性白质脑病在多发性硬化症(MS)中发生于 2 例同时接受干扰素β1a 治疗的患者,这引起了对这些疾病修正药物相互作用的关注,并导致建议避免同时使用这些药物。然而,I 型干扰素具有抗病毒作用。我们使用实时定量聚合酶链反应检测和定量外周血单个核细胞(PBMC)和 MS 患者尿液中的约翰·坎宁安病毒(JCV)DNA,以检验这样一种假设,即 MS 疾病修正药物(DMD)定性和定量改变 JCV 的流行率和病毒拷贝数。我们对 239 例患者进行了一项横断面研究,在该研究中,一次采集血液和尿液标本,对 37 例新诊断的、未经治疗的 MS 患者进行了纵向研究,在该研究中,在诊断时和治疗开始后 6 个月采集标本。仅在 2 例患者(0.07%)的 PBMC 中检测到 JCV DNA,但在该人群的尿液中(46.8%)普遍检测到。无论使用那他珠单抗(Copaxone®)还是干扰素-β 治疗(Avonex®、Betaseron®或 Rebif®),DMD 对血液或尿液中 JCV 的流行率或病毒拷贝数均无影响。由于接受其他治疗的患者数量较少,因此无法对其效果进行有意义的评价。即使对于干扰素-β,也没有观察到平台 DMD 对 JCV 流行率的明显影响。

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本文引用的文献

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Anti-JC virus antibodies: implications for PML risk stratification.抗-JC 病毒抗体:对 PML 风险分层的意义。
Ann Neurol. 2010 Sep;68(3):295-303. doi: 10.1002/ana.22128.
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Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors.400名健康献血者中多瘤病毒BK和JC感染及复制的患病率
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α干扰素和β干扰素可限制多瘤病毒JC在原代人胎儿神经胶质细胞中的复制:对进行性多灶性白质脑病治疗的意义。
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Interferon-beta treatment and active replication of the JC virus in relapsing-remitting multiple sclerosis patients.干扰素-β治疗与复发缓解型多发性硬化症患者中JC病毒的活跃复制
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JC virus detection in bodily fluids: clues to transmission.体液中JC病毒的检测:传播线索
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Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy.对接受那他珠单抗治疗的进行性多灶性白质脑病患者的评估。
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Innate immune recognition of viral infection.病毒感染的天然免疫识别
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Progression of progressive multifocal leukoencephalopathy despite treatment with beta-interferon.尽管使用了β-干扰素治疗,进行性多灶性白质脑病仍有进展。
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Virology. 2006 Feb 20;345(2):457-67. doi: 10.1016/j.virol.2005.10.012. Epub 2005 Nov 17.