Vernino S, Low P A, Fealey R D, Stewart J D, Farrugia G, Lennon V A
Department of Neurology, Mayo Clinic, Rochester, Minn 55905, USA.
N Engl J Med. 2000 Sep 21;343(12):847-55. doi: 10.1056/NEJM200009213431204.
Idiopathic autonomic neuropathy is a severe, subacute disorder with a presumed autoimmune basis. It is indistinguishable from the subacute autonomic neuropathy that may accompany lung cancer or other tumors. Autoantibodies specific for nicotinic acetylcholine receptors in the autonomic ganglia are potentially pathogenic and may serve as serologic markers of various forms of autoimmune autonomic neuropathy.
We tested serum from 157 patients with a variety of types of dysautonomia. Immunoprecipitation assays with iodine-125-labeled epibatidine and solubilized human neuroblastoma acetylcholine receptors were used to detect autoantibodies that bound to or blocked ganglionic receptors.
Ganglionic-receptor-binding antibodies were found in 19 of 46 patients with idiopathic or paraneoplastic autonomic neuropathy (41 percent), in 6 of 67 patients with postural tachycardia syndrome, idiopathic gastrointestinal dysmotility, or diabetic autonomic neuropathy (9 percent), and in none of 44 patients with other autonomic disorders. High levels of the binding antibodies correlated with more severe autonomic dysfunction (including the presence of tonic pupils). Levels of these antibodies decreased in patients who had clinical improvement. All seven patients with ganglionic-receptor-blocking antibodies had ganglionic-receptor-binding antibodies and had idiopathic or paraneoplastic autonomic neuropathy.
Seropositivity for antibodies that bind to or block ganglionic acetylcholine receptors identifies patients with various forms of autoimmune autonomic neuropathy and distinguishes these disorders from other types of dysautonomia. The positive correlation between high levels of ganglionic-receptor antibodies and the severity of autonomic dysfunction suggests that the antibodies have a pathogenic role in these types of neuropathy.
特发性自主神经病变是一种严重的亚急性疾病，推测有自身免疫基础。它与可能伴随肺癌或其他肿瘤的亚急性自主神经病变难以区分。自主神经节中烟碱型乙酰胆碱受体的特异性自身抗体具有潜在致病性，可能作为各种自身免疫性自主神经病变的血清学标志物。
我们检测了157例患有各种类型自主神经功能障碍患者的血清。采用碘-125标记的厄瓜多尔箭毒蛙毒素和溶解的人神经母细胞瘤乙酰胆碱受体进行免疫沉淀试验，以检测与神经节受体结合或阻断神经节受体的自身抗体。
在46例特发性或副肿瘤性自主神经病变患者中，有19例（41%）发现神经节受体结合抗体；在67例患有体位性心动过速综合征、特发性胃肠动力障碍或糖尿病性自主神经病变的患者中，有6例（9%）发现神经节受体结合抗体；而在44例患有其他自主神经疾病的患者中均未发现。高水平的结合抗体与更严重的自主神经功能障碍（包括强直性瞳孔的存在）相关。这些抗体的水平在临床症状改善的患者中下降。所有7例具有神经节受体阻断抗体的患者均有神经节受体结合抗体，且患有特发性或副肿瘤性自主神经病变。
与神经节乙酰胆碱受体结合或阻断神经节乙酰胆碱受体的抗体呈血清学阳性，可识别各种形式的自身免疫性自主神经病变患者，并将这些疾病与其他类型的自主神经功能障碍区分开来。高水平的神经节受体抗体与自主神经功能障碍的严重程度呈正相关，提示这些抗体在这些类型的神经病变中起致病作用。
