AUTOIMMUNE PARANEOPLASTIC SYNDROMES

自身免疫性副肿瘤综合征

• 批准号: 3175165
• 负责人: VANDA A LENNON
• 金额: $ 16.26万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-03-01 至 1987-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3175165
• 关键词: acetylcholine; autoantibody; autoimmune disorder; cancer complication; disease /disorder model; electrophysiology; human tissue; immunization; immunogenetics; monoclonal antibody; myasthenia gravis; neoplasm /cancer transplantation; nerve endings; neuromuscular disorder diagnosis; serology /serodiagnosis; small cell lung cancer; surface antigens; tissue /cell culture; tumor antigens

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)

兰伯特 - 伊东肌无力综合征（LES）是神经肌肉的疾病 乙酰胆碱的量化量不足的传播 （ACH）响应神经冲动。 它的病因仍然未知。 这种疾病的引人注目的特征包括支气管原理的高发病率 通常小细胞（燕麦 单元格类型（SCC）和自身抗体的高患病率（例如 特定的甲状腺和胃成分）。血浆的被动转移 来自患者到小鼠的免疫球蛋白会导致神经肌肉缺陷 类似于LE的传输。 我们的假设是LES神经肌肉传播的失败 对胆碱能神经元的自身免疫反应或相关的结果 结构，可以通过抗肿瘤免疫反应引发的结构 针对SCC的神经元相关的分化抗原。 我们计划学习 SCC在免疫学上确定肿瘤还是它们的 产品可以表达与胆碱能神经元有关的抗原。 血清来自 患有和无癌的LES患者将通过 SCC，胆碱能神经元和其他神经底物。 胆碱能神经 Torpreedo Califordica的电源器官将是 作为与LES相关的抗原的另一个潜在来源。 针对SCC和胆碱能神经元成分提出的单克隆抗体 将既可以用来识别和净化相关性的抗原。 该项目的目标是确定主要自身免疫的性质 LES异常。 一个相关的目标是建立LES的动物模型 那是：（1）将促进对负责机制的详细分析 对于LES中ACH量子的释放失败； （2）可能会产生血清学 测试LE和/或小细胞癌的诊断； （3）将允许 评估LE和/或小细胞癌的新治疗模式。 （IB）