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.

获得性免疫介导的多发性神经病，均为急性形式（格林 巴利综合症； GBS）和慢性形式（慢性炎症 脱髓鞘性多发性神经病； CIDP）代表了诊断挑战 有两个原因。 治疗策略的最新进展提供了重大意义 对此类患者有利。 这项研究的假设是 CIDP 和 GBS 中自身抗体特定靶点的识别 将有助于更好地了解这些疾病的免疫发病机制 疾病和用于诊断、预后和治疗的有用血清标志物 治疗。 虽然体液免疫系统和细胞免疫系统都受到影响 在这些疾病的发病机制中，最近的研究支持 体液免疫系统在发病机制中的主要作用。 我们有 最近发现人类β-微管蛋白是一个潜在的抗原靶点 在 CIDP 和 GBS 中。 我们计划定义 β-微管蛋白上的目标表位 CIDP 和 GBS 患者的血清中。 血清将被测试 使用与人β-微管蛋白的肽片段结合的抗体 ELISA 方法。 接下来，β-微管蛋白上的表位与 用 β-微管蛋白免疫后产生的诱导抗体将 使用相同的方法进行研究。 第三个目标是研究大 临床特征明确的 CIDP 和 GBS 患者队列 抗β微管蛋白患者的相关临床特征 抗体。 回顾性研究和前瞻性研究都将 解决抗体与 β-微管蛋白结合的存在和程度，以及 将其与年龄、性别、病程、所涉及的方式联系起来， 虚弱程度以及对治疗的反应。 最终目标将询问天然抗 β-微管蛋白抗体是否是 致病的。 患者 IgM 或 IgG 将被动转移 系统地对小鼠进行治疗。 在第二种模型中，将注射患者血清 局部进入大鼠坐骨神经。 动物将被研究 电生理学和神经形态学评估。