AUTOIMMUNE PARANEOPLASTIC SYNDROMES

Lambert-Eaton肌无力综合征（LES）是一种神经肌肉疾病， 乙酰胆碱量子释放不足的传输 (ACh)对神经冲动的反应 其病因仍然不明。 这种疾病的显著特征包括高发生率的支气管源性 癌（± 65%的患者），通常为小细胞癌（燕麦癌） 细胞）类型（SCC），以及自身抗体的高流行率（例如，到 特定的甲状腺和胃成分）。等离子体被动转移 免疫球蛋白从病人到小鼠导致神经肌肉缺陷， 类似于LES的传输。 我们的假设是LES中神经肌肉传递的失败 结果从自身免疫反应对胆碱能神经元或相关 结构，这可能是由抗肿瘤免疫反应引发的， 针对SCC的神经元相关分化抗原。 我们计划学习 免疫学检查以确定肿瘤或其 产物可以表达与胆碱能神经元相关的抗原。 血清 将测试患有和不患有癌症的LES患者与以下物质的反应性： SCC、胆碱能神经元和其他神经基质。 胆碱能神经 加州鱼雷的电子琴的终端将被 研究作为与LES相关的抗原的另一个潜在来源。 抗SCC和胆碱能神经元成分的单克隆抗体 将用于鉴定和纯化相关抗原。 该项目的目标是确定原发性自身免疫性 LES异常。 一个相关的目标是建立LES的动物模型 （1）将有助于详细分析负责 LES中ACh量子释放失败;（2）可能产生血清学 用于诊断LES和/或小细胞癌的测试;以及（3）将允许 评价LES和/或小细胞癌的新治疗模式。 （IB）

The Lambert-Eaton myasthenic syndrome (LES) is a disease of neuromuscular transmission in which there is a deficient quantal release of acetylcholine (ACh) in response to a nerve impulse. Its etiology remains unknown. Striking features of this disease include a high incidence of bronchogenic carcinoma (plus or minus 65% of patients), usually of the small cell (oat cell) type (SCC), and a high prevalence of autoantibodies (e.g., to specific thyroid and stomach constituents). Passive transfer of plasma immunoglobulins from patients to mice causes a defect in neuromuscular transmission similar to that of LES. Our hypothesis is that failure of neuromuscular transmission in the LES results from an autoimmune response against cholinergic neurons or related structures, which may be initiated by an antitumor immune response directed against a neuron-related differentation antigen of SCC. We plan to study SCC immunologically to determine whether or not the tumors or their products can express antigens related to cholinergic neurons. Sera from LES patients with and without carcinoma will be tested for reactivity with SCC, cholinergic neurons, and other neural substrates. Cholinergic nerve terminals from the electric organ of Torpedo californica will be investigated as another potential source of antigen relevant to LES. Monoclonal antibodies raised against SCC and cholinergic neuron components will be used both to identify and purify the antigens of relevance. This project's goal is to determine the nature of the primary autoimmune abnormality in LES. A related goal is to establish an animal model for LES that: (1) will facilitate detailed analysis of the mechanisms responsible for the failure of release of ACh quanta in LES; (2) may yield a serologic test for diagnosis of LES and/or small cell carcinoma; and (3) will allow evaluation of new modes of therapy for LES and/or small cell carcinoma. (IB)