HUMORAL IMMUNE MECHANISMS IN POLYNEUROPATHIES

多发性神经病的体液免疫机制

• 批准号: 2259660
• 负责人: Anne M Connolly
• 金额: $ 8.6万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-28 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2259660
• 关键词: Guillain Barre syndrome; antiantibody; antigen antibody reaction; autoantibody; biomarker; electrophysiology; enzyme linked immunosorbent assay; epitope mapping; human subject; humoral immunity; immunoglobulin G; immunoglobulin M; immunoglobulin structure; immunopathology; laboratory mouse; laboratory rat; longitudinal human study; monoclonal antibody; myelinopathy; nervous system disorder diagnosis; polyneuritis; synthetic peptide; tubulin; western blottings

Acquired immune-mediated polyneuropathies, both the acute form (Guillain Barre Syndrome; GBS) and the chronic form (Chronic Inflammatory Demyelinating Polyneuropathy; CIDP) represent a diagnostic challenge for two reasons. Recent advances in treatment strategies offer significant benefit to such patients. The hypothesis underlying this research is that identification of specific targets of autoantibodies in CIDP and GBS will provide a better understanding of the immune pathogenesis of these diseases and a useful serum marker for diagnosis, prognosis, and treatment. While both the humoral and cellular immune systems have been implicated in the pathogenesis of these diseases, recent research supports the primary role of humoral immune system in the pathogenesis. We have recently identified human beta-tubulin as a potential antigenic target in CIDP and GBS. We plan to define the target epitope/s on beta-tubulin in serum of patients with CIDP and GBS. Serums will be tested for antibody binding against peptide fragments of human beta-tubulin using ELISA methodology. Next, the epitopes on beta-tubulin that react with induced antibodies arising after immunization with beta-tubulin will be studied using the same methodology. The third aim is to study a large cohort of clinically well characterized CIDP and GBS patients and correlated clinical features of the patients with anti beta-tubulin antibodies. Both a retrospective study and prospective study will address presence and degree of antibody binding to beta-tubulin and correlate this with age, sex, duration of illness, modalities involved, degree of weakness, and response to treatment. The final aim will ask if natural anti beta-tubulin antibodies are pathogenic. Patient IgM or IgG will be passively transferred systemically to mice. In a second model, patient sera will be injected locally into rat sciatic nerve. Animals will be studied electrophysiologically and nerves evaluated morphologically.

获得的免疫介导的多神经病，两种急性形式（Guillain） Barre综合征； GBS）和慢性形式（慢性炎症 脱髓鞘多发性神经病； CIDP）代表了诊断性挑战 两个原因。 治疗策略的最新进展提供了重要的 对此类患者的好处。 这项研究为基础的假设是 鉴定CIDP和GBS自身抗体的特定靶标 将更好地了解这些免疫发病机理 疾病和有用的血清标记物用于诊断，预后和 治疗。 虽然涉及体液和细胞免疫系统 在这些疾病的发病机理中，最近的研究支持 体液免疫系统在发病机理中的主要作用。 我们有 最近将人β-微管蛋白确定为潜在的抗原靶标 在CIDP和GB中。 我们计划在β-微管蛋白上定义靶表位 在CIDP和GBS患者的血清中。 血清将进行测试 使用使用人β-微管蛋白肽片段的抗体结合使用 ELISA方法论。 接下来，与β-微管蛋白上的表位相同 用β-微管蛋白免疫后引起的诱导抗体将是 使用相同的方法进行了研究。 第三个目的是研究大型 临床表征良好的CIDP和GBS患者的队列以及 抗β-微管蛋白患者的临床特征 抗体。 回顾性研究和前瞻性研究都将 解决与β-微管蛋白结合的抗体的存在和程度 将此与年龄，性别，疾病持续时间，涉及的方式相关联， 无力程度和对治疗的反应。 最终目标将询问天然抗β-微管蛋白抗体是否是 致病性。 患者IgM或IgG将被动转移 系统地到小鼠。 在第二个模型中，将注入患者血清 局部进入大鼠坐骨神经。 将研究动物 电生理学和神经在形态学上评估。