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研究 25-羟维生素 D 与 Epstein-Barr 病毒和人类疱疹病毒 6 之间的可能联系在多发性硬化症患者中的作用。

Study of the possible link of 25-hydroxyvitamin D with Epstein-Barr virus and human herpesvirus 6 in patients with multiple sclerosis.

机构信息

Grupo Investigación EM, Hospital Clínico San Carlos, Instituto Investigación Sanitaria San Carlos (IdISSC), Madrid.

Servicio Neurología, Hospital Universitario Getafe, Getafe.

出版信息

Eur J Neurol. 2018 Dec;25(12):1446-1453. doi: 10.1111/ene.13749. Epub 2018 Aug 3.

Abstract

BACKGROUND AND PURPOSE

Although the causes of multiple sclerosis (MS) remain partially unknown, environmental and genetic factors are thought to play a role in its aetiopathogenesis. Hypovitaminosis D, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) infections have been described as possible MS triggers. Our aim was to analyse the possible link between 25-hydroxyvitamin D [25(OH)D] and viruses in patients with MS.

METHODS

We included 482 patients with MS in a 2-year study. Serum samples were collected to analyse 25(OH)D levels and, according to sample availability, antibody titres against EBV and HHV-6 by enzyme-linked immunosorbent assay. DNA was extracted from blood in order to analyse EBV and HHV-6 viral load by quantitative real-time polymerase chain reaction and to genotype MS-related single nucleotide polymorphisms (rs3135388, rs2248359 and rs12368653) when possible.

RESULTS

The 25(OH)D levels were significantly higher in the first semester of the year than in the second. Carriers of the risk allele rs2248359-C showed lower 25(OH)D levels than non-carriers. For EBV, viral load was significantly higher when 25(OH)D levels were low, demonstrating an inverse correlation between 25(OH)D levels and EBV load.

CONCLUSIONS

The 25(OH)D levels could be involved in the regulation of EBV replication/reactivation in patients with MS.

摘要

背景与目的

尽管多发性硬化症(MS)的病因仍部分未知,但环境和遗传因素被认为在其发病机制中起作用。维生素 D 缺乏症、 Epstein-Barr 病毒(EBV)和人类疱疹病毒 6(HHV-6)感染被描述为可能的 MS 触发因素。我们的目的是分析 MS 患者中 25-羟维生素 D [25(OH)D]与病毒之间的可能联系。

方法

我们在一项为期 2 年的研究中纳入了 482 名 MS 患者。采集血清样本以通过酶联免疫吸附试验分析 25(OH)D 水平,并根据样本可用性分析 EBV 和 HHV-6 的抗体滴度。从血液中提取 DNA,以便通过实时定量聚合酶链反应分析 EBV 和 HHV-6 病毒载量,并在可能的情况下分析与 MS 相关的单核苷酸多态性(rs3135388、rs2248359 和 rs12368653)的基因型。

结果

25(OH)D 水平在年初显著高于年中。与非携带者相比,风险等位基因 rs2248359-C 的携带者 25(OH)D 水平较低。对于 EBV,当 25(OH)D 水平较低时,病毒载量明显较高,表明 25(OH)D 水平与 EBV 载量之间存在负相关。

结论

25(OH)D 水平可能参与调节 MS 患者中 EBV 的复制/激活。

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