Immunopathogenesis of Multiple Sclerosis

多发性硬化症的免疫发病机制

• 批准号: 7497835
• 负责人: MICHAEL K RACKE
• 金额: $ 10.87万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-15 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7497835
• 关键词: B lymphocyte; T lymphocyte; cerebrospinal fluid; clinical research; disease /disorder etiology; human subject; immunopathology; immunosuppression; leukocyte activation /transformation; mitoxantrone; multiple sclerosis; myelinopathy; nerve /myelin protein; pathologic process; patient oriented research; role model

DESCRIPTION (provided by applicant): The studies which are outlined in this proposal represent a very exciting and ambitious plan to address the issues of the magnitude, fine specificity, and precise nature of the autoreactive T cell response in MS and further explore the potential contribution of clonally expanded CSF B cells to disease pathogenesis. Using highly innovative approaches we plan to characterize these responses at a single cell level and analyze the TCR usage and CSF B cell repertoire, specifically in the context of various therapeutic interventions. These studies will determine the effectiveness of immune reconstitution with respect to the response to myelin antigens and compare that with what happens to the immune response following more standard immune suppression using mitoxantrone. We will also be able to compare this information with the data we are generating on patients with RRMS receiving more standard immunomodulatory therapies. We anticipate that these studies will provide important information with regard to the immunopathogenesis of MS. Data from these studies will allow the PI to design clinical trials testing novel therapeutic agents for MS based on the translational studies. In addition, the proposed Award will allow the PI to concentrate his efforts on mentoring the next generation of clinician scientists focusing their efforts on multiple sclerosis.

描述（由申请人提供）：该提案中概述的研究代表了一个非常令人兴奋和雄心勃勃的计划，以解决MS中自动反应性T细胞反应的大小，精细和精确性的问题，并进一步探讨了克隆人扩展的CSF B细胞对疾病病原体的潜在贡献。我们计划使用高度创新的方法在单个细胞水平上表征这些反应并分析TCR使用和CSF B细胞库，特别是在各种治疗干预措施的背景下。这些研究将确定免疫重构对髓磷脂抗原反应的有效性，并将其与使用Mitoxantrone更加标准的免疫抑制后的免疫反应发生的情况进行比较。我们还将能够将这些信息与正在接受RRMS患者的数据进行比较，该患者接受了更多标准的免疫调节疗法。我们预计，这些研究将提供有关MS的免疫发病发生的重要信息。这些研究的数据将使PI根据翻译研究设计用于MS的新型治疗剂的临床试验。此外，拟议的奖项将使PI专注于指导下一代临床医生，将精力集中在多发性硬化症上。