Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies

Background: 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. Autoa ntibodies specific for nicotinic acetylcholine receptors in the autonomic g anglia are potentially pathogenic and may serve as serologic markers of var ious forms of autoimmune autonomic neuropathy. Methods: We tested serum from 157 patients with a variety of types of dysau tonomia. Immunoprecipitation assays with iodine-125-labeled epibatidine and solubilized human neuroblastoma acetylcholine receptors were used to detec t autoantibodies that bound to or blocked ganglionic receptors. Results: Ganglionic-receptor-binding antibodies were found in 19 of 46 pati ents with idiopathic or paraneoplastic autonomic neuropathy (41 percent), i n 6 of 67 patients with postural tachycardia syndrome, idiopathic gastroint estinal dysmotility, or diabetic autonomic neuropathy (9 percent), and in n one of 44 patients with other autonomic disorders. High levels of the bindi ng antibodies correlated with more severe autonomic dysfunction (including the presence of tonic pupils). Levels of these antibodies decreased in pati ents who had clinical improvement. All seven patients with ganglionic-recep tor-blocking antibodies had ganglionic-receptor-binding antibodies and had idiopathic or paraneoplastic autonomic neuropathy. Conclusions: Seropositivity for antibodies that bind to or block ganglionic acetylcholine receptors identifies patients with various forms of autoimmu ne 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 tha t the antibodies have a pathogenic role in these types of neuropathy. (N En gl J Med 2000;343:847-55.) (C) 2000, Massachusetts Medical Society.