Infection in Multiple Sclerosis (MS)

描述（由申请人提供）：该项目将研究微生物糖脂和酰化脑苷之间的结构和免疫学相似性（“分子拟态”的基础），我们已经表征了它们精确的化学结构，以及它们在髓磷脂中的大量存在。该研究将检查：(1)髓磷脂酰基碳水化合物与微生物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；(3)MS和对照患者循环中的淋巴细胞和CSF中的细胞免疫反应（T细胞、NKT细胞和先天免疫）。这项工作可以描述在脱髓鞘中起重要作用的新的和重要的分子结构的结构和功能，并可能在脱髓鞘中起致病作用。最理想的情况是，该项目可能导致确定一种机制，通过支原体感染CMS或身体其他部位，支原体启动导致炎性脱髓鞘的免疫事件，甚至直接引起炎症级联反应。这一发现也可能引发自身免疫性疾病的致病作用。此外，髓磷脂脑苷衍生物的测定提供了一种新的机会来测量髓磷脂成分与多发性硬化症的类型、分期和活动有关，可以为诊断和确定疾病活动提供有用的方法。

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.