Isolation of Clostridium perfringens type B in an individual at first clinical presentation of multiple sclerosis provides clues for environmental triggers of the disease.

Isolation of Clostridium perfringens type B in an individual at first clinical presentation of multiple sclerosis provides clues for environmental triggers of the disease.
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DOI:
10.1371/journal.pone.0076359
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Vartanian T
Vartanian T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Rumah KR;Linden J;Fischetti VA;Vartanian T

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我们从一名患有多发性硬化症(MS)且脑部磁共振成像(MRI)显示有活动性强化病灶的年轻女性身上分离出了B型产气荚膜梭菌,这是一种分泌ε毒素的杆菌。这一发现首次表明在人体内检测到了B型产气荚膜梭菌。ε毒素对血脑屏障(BBB)的亲和性以及与少突胶质细胞/髓鞘的结合,使其成为多发性硬化症新生病灶形成的一个引人关注的候选因素。我们对一组特征明确的多发性硬化症患者和健康对照者进行了检查,以了解胃肠道中产气荚膜梭菌毒素型的携带情况。大约50%的健康对照者体内存在人类共生的A型产气荚膜梭菌,而在多发性硬化症患者中仅为23%。我们检测了从两个组织库获取的血清和脑脊液,发现多发性硬化症患者对ε毒素的免疫反应性比健康对照者普遍高10倍,这表明多发性硬化症患者群体先前接触过ε毒素。产气荚膜梭菌的ε毒素在机制上符合多发性硬化症新生病灶的形成,因为这些病灶的特征是在没有适应性免疫细胞浸润的情况下血脑屏障通透性增加和少突胶质细胞死亡。
We have isolated Clostridium perfringens type B, an epsilon toxin-secreting bacillus, from a young woman at clinical presentation of Multiple Sclerosis (MS) with actively enhancing lesions on brain MRI. This finding represents the first time that C. perfringens type B has been detected in a human. Epsilon toxin’s tropism for the blood-brain barrier (BBB) and binding to oligodendrocytes/myelin makes it a provocative candidate for nascent lesion formation in MS. We examined a well-characterized population of MS patients and healthy controls for carriage of C. perfringens toxinotypes in the gastrointestinal tract. The human commensal Clostridium perfringens type A was present in approximately 50% of healthy human controls compared to only 23% in MS patients. We examined sera and CSF obtained from two tissue banks and found that immunoreactivity to ETX is 10 times more prevalent in people with MS than in healthy controls, indicating prior exposure to ETX in the MS population. C. perfringens epsilon toxin fits mechanistically with nascent MS lesion formation since these lesions are characterized by BBB permeability and oligodendrocyte cell death in the absence of an adaptive immune infiltrate.
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