The risk of relapses in multiple sclerosis during systemic infections

The risk of relapses in multiple sclerosis during systemic infections
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DOI:
10.1212/01.wnl.0000233834.09743.3b
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发表时间:
2006-08-22
期刊:
影响因子:
9.9
通讯作者:
Gilmore, Wendy
Gilmore, Wendy
中科院分区:
医学1区
文献类型:
--
作者:
Correale, Jorge;Fiol, Marcela;Gilmore, Wendy

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目的:评估 MS 患者全身感染 (SI) 期间多发性硬化症 (MS) 复发的风险、MRI 活性和 T 细胞反应。方法:作者前瞻性研究了 60 名多发性硬化症患者。 20 名患者在初次就诊以及 2 周和 12 周后接受了序贯 MRI 评估。在首次感染症状时以及 2、5、12 和 24 周后收集血样,并在感染性抗原 (Ag) 刺激后测量 IL-4、IL-10、IL-12、IFN-γ、TNF α、VLA-4、LFA-1、MMP-9 和 MMP-2 的产生。结果:SI 期间观察到复发风险和 MRI 活动增加。在与 SI 相关的恶化期间收集的样本中,PBMC 病毒或细菌 Ag 刺激后,IFN-γ、TNF α 和 IL-12 分泌细胞的数量、MMP-9 的血清浓度以及 VLA-4 和 LFA-1 的表达较高。 Transwell 分析表明,病毒刺激过程中产生的可溶性因子对髓磷脂特异性 T 细胞活性几乎没有影响。相比之下,在同源髓磷脂 Ag 存在的情况下,PBMC 病毒刺激诱导的最大效应器反应比单独 Ag 低 20 至 30 倍。结论:全身感染与 MS 复发风险、MRI 活性增加和 T 细胞激活之间存在显着相关性。此外,感染因子增加了髓磷脂特异性 T 细胞对同源 Ag 的敏感性。
Objectives: To assess the risk of multiple sclerosis (MS) relapses, MRI activity, and T cell responses during systemic infections ( SI) in patients with MS. Methods: The authors prospectively studied 60 patients with MS. Twenty patients were evaluated with sequential MRI on initial visit, and 2 and 12 weeks later. Blood samples were collected at first infection symptom and 2, 5, 12, and 24 weeks later, and production of IL-4, IL-10, IL-12, IFN-gamma, TNF alpha, VLA-4, LFA-1, MMP-9, and MMP-2 were measured after infectious antigens (Ag) stimulation. Results: Increased risk of relapse and MRI activity were observed during SI. Numbers of IFN-gamma, TNF alpha, and IL-12 secreting cells, serum concentrations of MMP-9, and expression of VLA-4 and LFA-1 after PBMC viral or bacterial Ag stimulation were higher in samples collected during exacerbations associated to SI. Transwell analysis demonstrated that soluble factors produced during viral stimulation have little effect on myelin specific T cells activity. In contrast, PBMC viral stimulation in the presence of cognate myelin Ag induces maximal effector responses at 20 to 30 times lower than the Ag alone. Conclusions: There was a significant association between systemic infections and risk of MS relapse, increased MRI activity, and T cells activation. Furthermore, infectious agents increased myelin specific T-cells sensitivity to cognate Ag.