INTERVENTIVE STRATEGIES FOR MYASTHENIA GRAVIS

重症肌无力（MG）及其动物模型 重症肌无力（EAMG）的特征是易疲劳， 随意肌的相对虚弱。 一个共同的特点， MG是T淋巴细胞依赖性的血清抗体应答， 由随意肌表达的抗原，乙酰胆碱受体（AchR）; 抗AChR自身抗体与AChR在神经肌肉 连接导致观察到的神经肌肉传递的损伤。 各种治疗方式用于治疗MG，最常见的是 免疫抑制化疗 然而，先天缺乏选择性， 所使用的药物限制了它们的用途。 建议的目标 该计划旨在识别和表征分子结构目标， 将允许开发更具选择性的免疫抑制剂。 由于MG是由T细胞依赖性抗AChR抗体应答引起的， 进行研究以鉴定B细胞和T细胞靶。 该计划的主要优势是，除了考试 关于B细胞和T细胞方面的问题，动物模型和 将探索人类患者系统;这将有助于相对 从实验室到临床的直接路径。 最终目标是 测试，在MG患者中，抗体-毒素缀合物（免疫毒素）， AChR反应性淋巴细胞的特异性。 我们很高兴能带来 来自4个不同部门的基础科学家， 探索疾病的细胞和分子免疫学方面， 临床医生可以直接接触到适当的患者， 与适当的临床环境一样。 我们认为，由于 围绕这组调查人员的情况，新的方法， 可以测试MG的免疫干预，这在任何地方都不可能 别的

Myasthenia gravis (MG) and its animal models Experimental Autoimmune Myasthenia Gravis (EAMG), are characterized by an ease of fatigability and relative weakness of voluntary muscles. A common feature associated with MG is T lymphocyte-dependent serum antibody responses against a self- antigen expressed by voluntary muscles, the acetylcholine receptor (AchR); the binding of anti-AChR autoantibodies to AChR at the neuromuscular junction results in the observed impairment of neuromuscular transmission. Various modalities of therapy are used to treat MG, most often immunosuppressive chemotherapy. However, the innate lack of selectivity of the drugs employed limits their usefulness. The goal of the proposed program is to identify and characterize molecular-structural targets that would allow the development of more selective immunosuppressive agents. Since MG is caused by a T cell-dependent anti-AChR antibody response, studies are to be performed to identify both B cell and T cell targets. The primary strength of the Program is that, in addition to the examination of both the B cell and T cell side of the problem, both animal models and human patient systems will be explored; this should facilitate a relatively direct path from the laboratory to the clinic. The eventual goal is to test, in MG patients, antibody-toxin conjugates (immunotoxins) with specificity for AChR-reactive lymphocytes. We are very excited to bring together, from 4 different departments, basic scientists with a history of exploring cellular and molecular immunological aspects of disease with clinicians that have direct access to both the appropriate patients as well as with the appropriate clinical setting. We believe that because of the circumstances surrounding this group of investigators, novel approaches to immune intervention in MG can be tested that would not be possible anywhere else.