HUMORAL IMMUNE MECHANISMS IN POLYNEUROPATHIES

获得性免疫介导的多发性神经病，两种急性形式(吉兰 Barre综合征(GBS)和慢性形式(慢性炎症性 脱髓鞘多神经病；CIDP)是诊断 有两个原因。治疗策略的最新进展提供了重要的 让这类患者受益。这项研究背后的假设是 CIDP和GBS自身抗体特异性靶点的确定 将有助于更好地理解这些病毒的免疫发病机制。 疾病和有用的血清标记物用于诊断、预后和 治疗。 虽然体液免疫系统和细胞免疫系统都牵连到 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β-微管蛋白是潜在的抗原靶点 在CIDP和GBS中。我们计划确定β-微管蛋白的目标表位/S 在CIDP和GBS患者的血清中。将对血清进行检测 与人β-微管蛋白多肽片段结合的抗体 酶联免疫吸附试验方法。接下来，与β-微管蛋白发生反应的表位 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。第三个目标是研究一个大型的 临床特征良好的CIDP和GBS患者的队列 抗β-微管蛋白相关临床特征的研究 抗体。回溯性研究和前瞻性研究都将 解决与β-微管蛋白和β-微管蛋白结合的抗体的存在和程度 这与年龄、性别、病程、涉及的方式、 虚弱程度和对治疗的反应。 最终目标将是询问天然的抗β-微管蛋白抗体是否 致病的。患者的免疫球蛋白M或免疫球蛋白将被被动转移 对老鼠来说是系统性的。在第二个模型中，患者血清将被注射 局部植入大鼠坐骨神经。将对动物进行研究 电生理学和神经形态学检查。

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.