Infection in Multiple Sclerosis (MS)

描述（由申请人提供）：本项目将研究微生物糖脂和酰化-β-糖苷之间的结构和免疫学相似性（“分子模拟”的基础），我们已经表征了它们的精确化学结构，以及它们在髓鞘中的大量存在。这项研究将审查：（1）髓鞘的酰基碳水化合物与微生物的结合之间的交叉反应性，（2）它们与MS CSF中发现的寡克隆免疫球蛋白的结合，和（3）MS和对照中循环中淋巴细胞和CSF中的细胞免疫应答（T细胞、NKT细胞和先天免疫）。这项工作可以描绘的结构和功能的新的和重要的分子结构，在脱髓鞘中发挥重要作用，并可能在脱髓鞘的病因作用。最理想的情况是，该项目可能导致定义支原体启动免疫事件的机制，该免疫事件导致炎症性脱髓鞘，甚至直接导致CMS或体内其他部位支原体感染的炎症级联反应。从这些发现中也可以看出引发自身免疫性疾病的致病作用。此外，髓鞘苷衍生物的测定提供了一个新的机会，以测量髓鞘成分的类型，阶段和活动的MS可以产生有用的方法，用于诊断和确定疾病的活动。

DESCRIPTION (provided by applicant): This project will examine the structural and immunological similarities (the basis of 'molecular mimicry') between microbial glycolipids and the acylated-cerebrosides that we have characterized for both their precise chemical structure, and their presence in a substantial amount in myelin. The study will examine: (1) the cross-reactivity between the binding of the acyl-carbohydrates of myelin and microbes, (2) their binding to the oligoclonal immunoglobulins found in MS CSF and (3) cellular immune responses (T cells, NKT cells and innate immunity) in lymphocytes in the circulation and in CSF in MS and controls. This work can delineate both the structure and function of novel and significant molecular structures that play important roles in demyelination and may play a causative role in demyelination. Optimally, the project could lead to defining a mechanism by which mycoplasmas initiate the immune events that lead to inflammatory demyelination or even directly cause the inflammatory cascade by mycoplasma infection of CMS or elsewhere in the body. A pathogenic role in triggering the autoimmune disorder could also emerge from the findings. Furthermore, an assay of the myelin cerebroside derivatives that offers a novel opportunity to measure myelin constituents in relation to type, stage, and activity of MS could yield useful approaches for diagnosis and determination of disease activity.