Association between parasite infection and immune responses in multiple sclerosis
Association between parasite infection and immune responses in multiple sclerosis
复制标题
DOI：
10.1002/ana.21067
复制
发表时间：
2007-02-01
影响因子：
11.2
通讯作者：
Farez, Mauricio
中科院分区：
文献类型：
--
作者：
Correale, Jorge;Farez, Mauricio
目的：探讨寄生虫感染是否与多发性硬化症(MS)病情恶化次数减少和免疫反应改变有关。方法：采用前瞻性双队列研究方法，对12例伴有嗜酸性粒细胞增多症的MS患者的临床病程和放射学表现进行评估。所有患者均有寄生虫感染，粪便标本呈阳性。在所有寄生虫感染的MS患者中，在前两年中没有出现嗜酸性粒细胞增多症。每隔3至6个月监测一次嗜酸性粒细胞计数。当计数增加时，患者被纳入研究。采用酶联免疫斑点法(ELISPOT)检测髓鞘碱性蛋白特异性外周血单个核细胞产生IL-4、IL-10、IL-12、转化生长因子(TGF)-β和干扰素-γ的水平。结果：在4.6年的随访期内，与未感染的MS患者相比，寄生虫感染的MS患者的病情加重次数明显减少，残疾评分的差异也很小，磁共振成像的改变也更少。此外，感染的MS患者外周血髓鞘碱性蛋白特异性反应显示，与未感染的患者相比，IL-10和TGF-β显著增加，IL-12和干扰素-γ的分泌细胞减少。从感染者克隆的髓鞘碱性蛋白特异性T细胞的特征是不产生IL-2和IL-4，但高分泌IL-10和/或转化生长因子-β，显示出与T细胞亚群TR1和Th3相似的细胞因子谱。此外，与未感染的MS患者相比，感染患者的CD4(+)CD25(+)FoxP3(+)T细胞克隆频率显著增加。最后，在感染的MS患者的T细胞中未检测到分泌转化生长因子-β的Smad7信使RNA。解释：IL-10和转化生长因子-β的产生增加，以及CD25(+)CD4(+)FoxP3+T细胞的诱导，表明在寄生虫感染过程中诱导的调节性T细胞可以改变MS的进程。
Objective: To assess whether parasite infection is correlated with a reduced number of exacerbations and altered immune reactivity in multiple Sclerosis (MS).Methods: A prospective, double-cohort study was performed to assess the clinical course and radiological findings in 12 MS patients presenting associated eosinophilia. All patients presented parasitic infections with Positive stool specimens. In all parasite-infected MS patients, the eosinophilia was not present during the 2 previous years. Eosinophil counts were monitored at 3- to 6-month intervals. When counts became elevated, patients were enrolled in the study. Interleukin (IL)-4, IL-10, IL-12, transforming growth factor (TGF)-beta, and interferon-gamma production by myelin basic protein-specific peripheral blood mononuclear cells were studied using enzyme-linked immunospot (ELISPOT). FoxP3 and Smad7 expression were studied by reverse-transcriptase polymerase chain reaction.Results: During a 4.6-year follow-up period, parasite-infected MS patients showed a significantly lower number of exacerbations, minimal variation in disability scores, as well as fewer magnetic resonance imaging changes when compared with uninfected MS patients. Furthermore, myelin basic protein-specific responses in peripheral blood showed a significant increase in IL-10 and TGF-beta and a decrease in IL-12 and interferon-gamma-secreting cells in infected MS patients compared with noninfected patients. Myelin basic protein-specific T cells cloned from infected subjects were characterized by the absence of IL-2 and IL-4 production, but high IL-10 and/or TGF-beta secretion, showing a cytokine profile similar to the T-cell subsets Tr1 and Th3. Moreover, cloning frequency of CD4(+) CD25(+) FoxP3(+) T cells was substantially increased in infected patients compared with uninfected MS subjects. Finally, Smad7 messenger RNA was not detected in T cells from infected MS patients secreting TGF-beta.Interpretation: Increased production of IL-10 and TGF-beta, together with induction of CD25(+) CD4(+) FoxP3+ T cells, suggests that regulatory T cells induced during parasite infections can alter the course of MS.