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多发性硬化症的特定病毒病因:一种病毒,一种疾病。

A specific viral cause of multiple sclerosis: one virus, one disease.

作者信息

Lipton Howard L, Liang Zhiguo, Hertzler Shannon, Son Kyung-No

机构信息

Department of Neurology, University of Illinois at Chicago, Chicago, IL 60612-7344, USA.

出版信息

Ann Neurol. 2007 Jun;61(6):514-23. doi: 10.1002/ana.21116.

Abstract

"Multiple sclerosis is an autoimmune disease," is heard so often that it is widely accepted as fact by the current generation of students and physicians. Yet, although it is undisputed that multiple sclerosis (MS) is immune mediated, an autoimmune mechanism remains unproven. Immune-mediated tissue damage can also result from viral infections in which the host immune response is directed to viral rather than self proteins, or as a consequence of nonspecific or bystander immune responses that change the local cytokine environment. Increasing evidence suggests that poorly controlled host immune responses account for much of the tissue damage in chronic infections, and it has been postulated that a similar mechanism may underlie many chronic diseases with features suggestive of an infectious causative factor, including MS. A recent study suggesting that oligodendrocyte death accompanied by microglial activation is the primary event in new MS lesion formation, rather than lymphocyte infiltration, could change the current mindset almost exclusively focused on autoimmunity. This review presents the rationale for considering MS a single disease caused by one virus, as well as the anticipated pattern of a persistent central nervous system infection, the application of Koch's postulates to viral discovery in MS as the causative agent, and tissue culture-independent genotypic approaches to viral discovery in MS.

摘要

“多发性硬化症是一种自身免疫性疾病”,这句话被频繁提及,以至于当代学生和医生都普遍将其当作事实接受。然而,尽管多发性硬化症(MS)由免疫介导这一点毫无争议,但自身免疫机制仍未得到证实。免疫介导的组织损伤也可能源于病毒感染,在这种情况下宿主免疫反应针对的是病毒而非自身蛋白,或者是由于改变局部细胞因子环境的非特异性或旁观者免疫反应。越来越多的证据表明,宿主免疫反应控制不佳是慢性感染中许多组织损伤的主要原因,并且有人推测,类似的机制可能是许多具有感染性致病因素特征的慢性疾病(包括MS)的基础。最近一项研究表明,少突胶质细胞死亡伴随小胶质细胞激活是新的MS病灶形成中的主要事件,而非淋巴细胞浸润,这可能会改变目前几乎完全专注于自身免疫的思维模式。本综述阐述了将MS视为由一种病毒引起的单一疾病的理论依据,以及持续性中枢神经系统感染的预期模式、将科赫法则应用于MS中作为病原体的病毒发现,以及在MS中发现病毒的非组织培养基因型方法。

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