Immune-mediated genesis of multiple sclerosis
Immune-mediated genesis of multiple sclerosis
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DOI：
10.1016/j.jtauto.2020.100039
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Cavallo, Salvatore
中科院分区：
文献类型：
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作者：
Cavallo, Salvatore
多发性硬化症（MS）被广泛认为是一种影响中枢神经系统神经元髓鞘结构的自身免疫性疾病。被认为是这一自身免疫过程靶点的自身抗原有：髓磷脂基础蛋白、抗蛋白脂蛋白、抗髓磷脂相关糖蛋白和基于抗髓磷脂的少突细胞基础蛋白。大量证据支持在HLA易感基因受试者中，由一种或多种病毒或细菌微生物剂引发的对神经髓鞘结构自身抗原的免疫耐受失调的观点。许多将MS与特定HLA单倍型联系起来的研究强调了MS的遗传易感性。此外，大量证据支持这样一个事实，即多发性硬化症可能是一种或多种病毒或细菌感染的结果，如麻疹病毒、EBV、HHV6、HZV、肺炎衣原体、幽门螺杆菌和其他微生物病原体。微生物群元素似乎也在疾病的决定性中发挥作用，作为致病因素或保护因素。当外来微生物抗原和自身抗原在HLA基因主体中发生分子模仿时，自身免疫发病过程可能发生。在这种情况下，抗原呈递细胞会诱导特异性Th克隆的激活，引起外源抗原和自身抗原之间的交叉反应，从而导致自身免疫反应。
Multiple sclerosis (MS) is widely acknowledged to be an autoimmune disease affecting the neuronal myelin structure of the CNS. Autoantigens recognized as the target of this autoimmune process are: myelin basal protein, anti-proteolipid protein, antimyelin-associated glycoprotein and antimyelin-based oligodendrocytic basic protein. Ample evidence supports the idea of a dysregulation of immunological tolerance towards self-antigens of neuronal myelin structure triggered by one or more viral or bacterial microbial agents in predisposed HLA gene subjects. Genetic predisposition to MS has been highlighted by numerous studies associating the disease to specific HLA haplotypes. Moreover, a wide range of evidence supports the fact that MS may be consequence of one or more viral or bacterial infections such as measles virus, EBV, HHV6, HZV, Chlamydia pneumoniae, Helicobacter Pylori, and other microbial agents. Microbiota elements also seems to have a role on the determinism of the disease as a pathogenic or protective factor. The autoimmune pathogenetic process could arise when a molecular mimicry between a foreign microbial antigen and an auto-antigen occurs in an HLA gene subject competent for that particular antigen. The antigen-presenting cells in this case would induce the activation of a specific Th clone causing a cross-reaction between a foreign antigen and an autoantigen resulting in an autoimmune response.