HUMORAL IMMUNE MECHANISMS IN POLYNEUROPATHIES

获得性免疫介导的多发性神经病，包括急性形式（Guillain Barre综合征; GBS）和慢性形式（慢性炎症性 脱髓鞘性多发性神经病; CIDP）代表了对以下疾病的诊断挑战： 两个原因第 治疗策略的最新进展提供了重要的 对这样的病人有好处。 这项研究的假设是 CIDP和GBS中自身抗体的特异性靶点的鉴定 将提供一个更好的了解免疫发病机制，这些 疾病和一个有用的血清标志物的诊断，预后， 治疗 虽然体液和细胞免疫系统都与 在这些疾病的发病机制中，最近的研究支持了 体液免疫系统在发病机制中的主要作用。 我们有 最近鉴定人β-微管蛋白为潜在的抗原靶点 CIDP和GBS。 我们计划确定β-微管蛋白上的靶表位 CIDP和GBS患者的血清中。 将检测血清 抗体结合人β-微管蛋白的肽片段 ELISA方法学。 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被 使用相同的方法进行研究。 第三个目标是研究一个大的 临床特征良好的CIDP和GBS患者队列， 抗β-微管蛋白抗体患者的相关临床特征 抗体的 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， 将其与年龄、性别、疾病持续时间、所涉及的模式相关联， 虚弱程度和对治疗的反应。 最终的目标是询问天然的抗β-微管蛋白抗体是否 致病的 患者IgM或IgG将被动转移 对小鼠的全身性影响。 在第二个模型中，将患者血清注射到 局部进入大鼠坐骨神经。 将研究动物 电生理学和神经形态学评价。

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.