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Autoantibodies to Ganglionic Acetylcholine Receptors in Autoimmune Autonomic Neuropathies
Open accessAbstract
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. 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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“Seropositivity for antiganglionic acetylcholine receptor antibodies is the serological hallmark of autoimmune autonomic ganglionopathy.”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [433]
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“Other antibodies, including ganglionic acetylcholine receptor antibodies and CRMP-5 (CV2), have also been associated with enteric dysmotility in paraneoplastic/autoimmune contexts (Blackburn et al., 2019; Vernino et al., 2000), and neuropathologic studies show that some patients have more extensive involvement (Sodhi et al., 1989).”
From Autonomic nervous system and gastrointestinal manifestations with an emphasis on gastric dysfunction (2026) · cites this paper as Vernino et al., 2000
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Metadata
- Authors
- Vernino, S., Low, P. A., Fealey, R. D., Stewart, J. D., Farrugia, G., & Lennon, V. A.
- Affiliations
- Mayo Clinic (US)
- Montreal Neurological Institute and Hospital (CA)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2000-09-21
- Volume
- 343
- Issue
- 12
- Pages
- 847-855
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2341201500
- Cited by
- 674
- References
- 34
- Citations by year
- 2026: 16 · 2025: 10 · 2024: 33 · 2023: 20 · 2022: 26 · 2021: 36 · 2020: 28 · 2019: 30 · 2018: 32 · 2017: 24 · 2016: 21 · 2015: 21 · 2014: 19 · 2013: 31 · 2012: 27
- FWCI
- 12.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Autoimmune Neurological Disorders and Treatments
- Health Sciences › Medicine › Clinical Neurology › Peripheral Neuropathies and Disorders
- Health Sciences › Medicine › Clinical Neurology › Myasthenia Gravis and Thymoma
- Keywords
- autoantibodies, postural orthostatic tachycardia syndrome, diabetic autonomic neuropathy, gastrointestinal motility disorders, autonomic dysfunction, serological markers, epibatidine, tonic pupil
- MeSH terms
- Adult, Aged, Autoantibodies, Autoimmune Diseases, Autonomic Nervous System Diseases, Diabetic Neuropathies, Female, Follow-Up Studies, Ganglia, Autonomic, Humans, Male, Middle Aged, Receptors, Nicotinic, Sensitivity and Specificity, Severity of Illness Index, Sweating, Paraneoplastic Syndromes, Nervous System
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