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那他珠单抗动员的 CD34+祖细胞不是 JC 病毒的相关储存库。

CD34+ progenitor cells mobilized by natalizumab are not a relevant reservoir for JC virus.

机构信息

Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany.

出版信息

Mult Scler. 2011 Feb;17(2):151-6. doi: 10.1177/1352458510385834. Epub 2010 Nov 15.

Abstract

BACKGROUND

Progressive multifocal leukoencephalopathy (PML) is associated with natalizumab treatment in patients with multiple sclerosis (MS). It has been hypothesized that natalizumab mobilizes JC virus (JCV)-infected haematopoietic progenitor cells mediating viraemia and subsequently this disease.

OBJECTIVE

The objective of this study was to investigate peripheral haematopoietic progenitor cells for evidence of JCV DNA in MS patients treated with natalizumab.

METHODS

We assessed JCV and cytomegalovirus (CMV) DNA in magnetically separated CD34+ haematopoietic progenitor cells, peripheral blood mononuclear cells and plasma of 67 natalizumab-treated patients with MS and six PML patients.

RESULTS

Viral DNA was not detectable in CD34+ haematopoietic progenitor or peripheral blood mononuclear cells from any sample. Two plasma samples from patients with MS while undergoing natalizumab treatment were JCV-positive. In one case clinically manifest PML developed 8 months thereafter.

CONCLUSIONS

Our findings do not support the hypothesis that natalizumab mobilizes JC virus-infected CD34+ cells from the bone marrow mediating JC viraemia. Notably, JC viraemia was detected in one patient with MS prior to developing clinical PML. This warrants further study.

摘要

背景

进展性多灶性白质脑病(PML)与多发性硬化症(MS)患者的那他珠单抗治疗相关。据推测,那他珠单抗动员 JC 病毒(JCV)感染的造血祖细胞介导病毒血症,进而导致这种疾病。

目的

本研究旨在研究接受那他珠单抗治疗的 MS 患者的外周造血祖细胞中是否存在 JCV DNA。

方法

我们评估了 67 名接受那他珠单抗治疗的 MS 患者和 6 名 PML 患者的磁分离 CD34+造血祖细胞、外周血单个核细胞和血浆中的 JCV 和巨细胞病毒(CMV)DNA。

结果

在任何样本的 CD34+造血祖细胞或外周血单个核细胞中均未检测到病毒 DNA。在接受那他珠单抗治疗的 2 名 MS 患者的 2 份血浆样本中,JCV 呈阳性。其中一例 8 个月后出现临床 PML。

结论

我们的研究结果不支持那他珠单抗动员骨髓中 JCV 感染的 CD34+细胞介导 JCV 病毒血症的假说。值得注意的是,在发生临床 PML 之前,1 例 MS 患者中已检测到 JC 病毒血症。这需要进一步研究。

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