Immunization with neuronal nicotinic acetylcholine receptor induces neurological autoimmune disease.
Immunization with neuronal nicotinic acetylcholine receptor induces neurological autoimmune disease.
复制标题
用神经元烟碱乙酰胆碱受体进行免疫会诱发神经性自身免疫性疾病。
DOI：
10.1172/jci17429
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Vernino,Steven
中科院分区：
文献类型：
--
作者：
Lennon,VandaA;Ermilov,LeonidG;Szurszewski,JosephH;Vernino,Steven
Neuronal nicotinic AChRs (nAChRs) are implicated in the pathogenesis of diverse neurological disorders and in the regulation of small-cell lung carcinoma growth. Twelve subunits have been identified in vertebrates, and mutations of one are recognized in a rare form of human epilepsy. Mice with genetically manipulated neuronal nAChR subunits exhibit behavioral or autonomic phenotypes. Here, we report the first model of an acquired neuronal nAChR disorder and evidence for its pertinence to paraneoplastic neurological autoimmunity. Rabbits immunized once with recombinant α3 subunit (residues 1–205) develop profound gastrointestinal hypomotility, dilated pupils with impaired light response, and grossly distended bladders. As in patients with idiopathic and paraneoplastic autoimmune autonomic neuropathy, the severity parallels serum levels of ganglionic nAChR autoantibody. Failure of neurotransmission through abdominal sympathetic ganglia, with retention of neuronal viability, confirms that the disorder is a postsynaptic channelopathy. In addition, we found ganglionic nAChR protein in small-cell carcinoma lines, identifying this cancer as a potential initiator of ganglionic nAChR autoimmunity. The data support our hypothesis that immune responses driven by distinct neuronal nAChR subtypes expressed in small-cell carcinomas account for several lung cancer–related paraneoplastic disorders affecting cholinergic systems, including autoimmune autonomic neuropathy, seizures, dementia, and movement disorders.
