Immunization with neuronal nicotinic acetylcholine receptor induces neurological autoimmune disease
Open accessAbstract
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 alpha3 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.
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Experimental immunization with neuronal nicotinic acetylcholine receptors can reproduce autonomic and GI dysfunction in animal models, supporting a pathogenic role for some antibody-mediated processes.
“Experimental immunization with neuronal nicotinic acetylcholine receptors can reproduce autonomic and GI dysfunction in animal models, supporting a pathogenic role for some antibody-mediated processes (Lennon et al., 2003).”
From Autonomic nervous system and gastrointestinal manifestations with an emphasis on gastric dysfunction (2026) · cites this paper as Lennon et al., 2003
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References 35 · Cited by 178
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- Musunuru, K., and Darnell, R.B. 2001. Review. Paraneoplastic neuro- logic disease antigens: RNA-binding proteins and signaling proteins in neuronal degeneration. Annu. Rev. Neurosci. 24:239-262.
- Vernino, S., Kryzer, T.J., and Lennon, V.A. 2002. Autoimmune autonomic neuropathy and neuromuscular hyperexcitability disorders. In Manual of clinical and laboratory immunology. 6th edition. N.R. Rose, R.G. Hamil- ton, and B. Detrick, editors. ASM Press. Washington, DC, USA. 1013-1017.
- Szurszewski, J.H., and Miller, S.M. 1994. Physiology of prevertebral gan- glia. In Physiology of the gastrointestinal tract. 3rd edition. L.R. Johnson, edi- tor. Raven Press. New York, New York, USA. 795-877.
- Fukunaga, H., Engel, A.G., Lang, B., Newsom-Davis, J., and Vincent, A. 1983. Passive transfer of Lambert-Eaton myasthenic syndrome with IgG from man to mouse depletes the presynaptic membrane active zones. Proc. Natl. Acad. Sci. U. S. A. 80:7636-7640.
- Xu, W., et al. 1999. Megacystis, mydriasis, and ion channel defect in mice lacking the alpha3 neuronal nicotinic acetylcholine receptor. Proc. Natl. Acad. Sci. U. S. A. 96:5746-5751.
- Brimijoin, S., and Lennon, V.A. 1990. Autoimmune preganglionic sym- pathectomy induced by acetylcholinesterase antibodies. Proc. Natl. Acad. Sci. U. S. A. 87:9630-9634.
- Maneckjee, R., and Minna, J.D. 1990. Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines. Proc. Natl. Acad. Sci. U. S. A. 87:3294-3298.
- Chini, B., Clementi, F., Hukovic, N., and Sher, E. 1992. Neuronal-type α- bungarotoxin receptors and the α5-nicotinic receptor subunit gene are expressed in neuronal and nonneuronal human cell lines. Proc. Natl. Acad. Sci. U. S. A. 89:1572-1576.
- Klein, C.M., et al. 2003. The spectrum of autoimmune autonomic neu- ropathies. Ann. Neurol. In press.
- Authors
- Lennon, V. A., Ermilov, L. G., Szurszewski, J. H., & Vernino, S.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Lennon, Vanda A.
- Venue
- Journal of Clinical Investigation
- Published
- 2003-03-15
- Volume
- 111
- Issue
- 6
- Pages
- 907-913
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC153771
- OpenAlex
- W2108349925
- Cited by
- 178
- References
- 35
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 8 · 2023: 5 · 2022: 6 · 2021: 11 · 2020: 5 · 2019: 7 · 2018: 6 · 2017: 5 · 2016: 7 · 2015: 3 · 2014: 11 · 2013: 8 · 2012: 6
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Clinic
- National Institutes of Health (5r01ca037343-11)
- National Cancer Institute (CA-37343)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK17636)
- National Institute of Neurological Disorders and Stroke (K08NS002247, NS-02247)
- Topics
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Neurology › Myasthenia Gravis and Thymoma
- Keywords
- neuronal nicotinic acetylcholine receptors, alpha3 subunit, small cell lung cancer, gastrointestinal hypomotility, pupil dilation, bladder distension, cholinergic system, seizures, dementia, movement disorders
- MeSH terms
- Animals, Autoantibodies, Autonomic Nervous System Diseases, Urinary Bladder Diseases, Eye Diseases, Female, Ganglia, Autonomic, Humans, Immunization, Lung Neoplasms, Rabbits, Receptors, Nicotinic, Tumor Cells, Cultured, Carcinoma, Small Cell, Autoimmune Diseases of the Nervous System
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