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-伊顿肌无力综合征 (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。 其病因尚不清楚。 这种疾病的显着特征包括支气管原发性高发病率 癌（正负 65% 的患者），通常为小细胞癌（燕麦 细胞）类型（SCC），以及自身抗体的高流行（例如， 特定的甲状腺和胃成分）。血浆被动转移 从患者到小鼠的免疫球蛋白导致神经肌肉缺陷 传输方式与 LES 类似。 我们的假设是 LES 中的神经肌肉传递失败 针对胆碱能神经元或相关神经元的自身免疫反应的结果 结构，这可能是由抗肿瘤免疫反应直接启动的 对抗 SCC 神经元相关分化抗原。 我们计划学习 SCC 免疫学以确定肿瘤或其是否存在 产品可以表达与胆碱能神经元相关的抗原。 血清来自 患有或不患有癌症的 LES 患者将接受以下反应性测试： 鳞状细胞癌、胆碱能神经元和其他神经基质。 胆碱能神经 加州鱼雷电子琴的端子将 作为 LES 相关抗原的另一个潜在来源进行研究。 针对鳞状细胞癌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疾病的性质 LES 异常。 一个相关的目标是建立 LES 动物模型 (1) 将有助于对负责机制进行详细分析 LES 中乙酰胆碱量子释放失败； (2) 可能会产生血清学结果 诊断 LES 和/或小细胞癌的测试；和（3）将允许 评估 LES 和/或小细胞癌的新治疗模式。 （IB）