Experimental autoimmune autonomic neuropathy
Experimental autoimmune autonomic neuropathy
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DOI：
10.1152/jn.00408.2003
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发表时间：
2003-09-01
影响因子：
2.5
通讯作者：
Lennon, VA
中科院分区：
文献类型：
--
作者：
Vernino, S;Low, PA;Lennon, VA
在亚急性自主神经功能衰竭患者血清中发现高滴度的神经节烟碱乙酰胆碱受体（nAChR）特异性抗体。这种临床病症被称为自身免疫性自主神经病变（AAN）。用神经元nAChR α 3亚基融合蛋白免疫的兔子产生神经节nAChR抗体并发展自主神经衰竭（实验性AAN或EAAN）。我们使用自主神经功能的定量测量来证明神经元nAChR自身免疫的动物模型概括了人类AAN的主要自主神经功能。兔的自主神经功能障碍的严重程度范围从孤立的心迷走神经损伤到严重的泛自主神经功能衰竭，包括固定性瞳孔散大、胃轻瘫、干眼、心率变异性受损、低血压和低血浆儿茶酚胺。自主神经功能衰竭的严重程度与血清抗体水平相关。上级颈神经节和肌间神经丛神经元的免疫组织化学染色显示完整的突触前神经末梢和完整的突触后神经元含有细胞质nAChR，但缺乏表面nAChR。这些发现定义了这种新型动物模型的自主生理学和组织病理学，并支持人类AAN是由神经节nAChR抗体引起的神经节胆碱能突触传递障碍的概念。
Antibodies specific for the neuronal ganglionic nicotinic acetylcholine receptor ( nAChR) are found in high titer in serum of patients with subacute autonomic failure. This clinical disorder is known as autoimmune autonomic neuropathy (AAN). Rabbits immunized with a neuronal nAChR alpha3 subunit fusion protein produce ganglionic nAChR antibodies and develop autonomic failure ( experimental AAN, or EAAN). We used quantitative measures of autonomic function to demonstrate that this animal model of neuronal nAChR autoimmunity recapitulates the cardinal autonomic features of AAN in humans. The severity of dysautonomia in the rabbit ranges from isolated cardiovagal impairment to severe panautonomic failure with fixed mydriasis, gastroparesis, dry eyes, impaired heart rate variability, hypotension, and low plasma catecholamines. The severity of autonomic failure correlates with serum antibody levels. Immunohistochemical staining of superior cervical ganglia and myenteric plexus neurons demonstrates intact presynaptic nerve terminals and intact postsynaptic neurons containing cytoplasmic nAChR, but lacking surface nAChR. These findings define the autonomic physiology and histopathology of this novel animal model and support the concept that AAN in humans is a disorder of ganglionic cholinergic synaptic transmission caused by ganglionic nAChR antibodies.