Neuronal nicotinic ACH receptor antibody in subacute autonomic neuropathy and cancer-related syndromes

Steven Vernino, Jill Adamski, Thomas J. Kryzer, Robert D. Fealey, Vanda A. Lennon

Research output: Contribution to journalArticle

176 Citations (Scopus)

Abstract

Background: Autoantibodies specific for the acetylcholine receptor (AChR) of skeletal muscle (containing the α1 subunit) impair neuromuscular transmission in myasthenia gravis (MG). AChRs mediating fast synaptic transmission through autonomic ganglia are structurally similar to muscle AChR, but contain the α3 subunit. We propose that ganglionic AChR autoimmunity may cause dysautonomia. Objective: To test serum of patients with autonomic neuropathy for autoantibodies of neuronal ganglionic AChR specificity. Methods: We developed an immunoprecipitation radioassay by complexing epibatidine (125I-labeled high affinity agonist) to a Triton X- 100-solubilized AChR antigen from peripheral neuroblastoma membranes. Monoclonal rat immunoglobulins (IgG) specific for muscle or neuronal AChRs validated the assay's specificity. We tested serum from 52 healthy subjects, 12 patients with subacute autonomic neuropathy, and 248 patients with other neurologic disorders. Results: Twelve patients had antibodies that bound unequivocally to ganglionic AChR. Five had subacute autonomic neuropathy, and three (of six tested) had Isaacs' syndrome; four of these eight had a carcinoma (lung, bladder, rectum, thyroid). The remaining four seropositive patients (two Lambert-Eaton syndrome, one dementia, one sensory neuronopathy) all had Ca2+ channel antibodies and three had small cell lung carcinoma. No healthy subject had ganglionic AChR antibodies, nor did 62 patients with MG and muscle AChR antibodies. Conclusion: Neuronal AChR antibodies are a novel serologic marker of neurologic autoimmunity. The pathogenicity of neuronal AChR autoantibodies in autonomic neuropathy, Isaacs' syndrome, or other neurologic disorders remains to be shown, as has been demonstrated for muscle AChR antibodies in MG. An autoimmune and potentially paraneoplastic etiology is implicated in seropositive patients.

Original languageEnglish (US)
Pages (from-to)1806-1813
Number of pages8
JournalNeurology
Volume50
Issue number6
StatePublished - Jun 1998

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Nicotinic Receptors
Cholinergic Receptors
Antibodies
Neoplasms
Myasthenia Gravis
Isaacs Syndrome
Autoantibodies
Muscles
epibatidine
Nervous System Diseases
Autoimmunity
Healthy Volunteers
Lambert-Eaton Myasthenic Syndrome
Autonomic Ganglia
Primary Dysautonomias
Small Cell Lung Carcinoma
Octoxynol
Serum
Neuroblastoma
Immunoprecipitation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Vernino, S., Adamski, J., Kryzer, T. J., Fealey, R. D., & Lennon, V. A. (1998). Neuronal nicotinic ACH receptor antibody in subacute autonomic neuropathy and cancer-related syndromes. Neurology, 50(6), 1806-1813.

Neuronal nicotinic ACH receptor antibody in subacute autonomic neuropathy and cancer-related syndromes. / Vernino, Steven; Adamski, Jill; Kryzer, Thomas J.; Fealey, Robert D.; Lennon, Vanda A.

In: Neurology, Vol. 50, No. 6, 06.1998, p. 1806-1813.

Research output: Contribution to journalArticle

Vernino, S, Adamski, J, Kryzer, TJ, Fealey, RD & Lennon, VA 1998, 'Neuronal nicotinic ACH receptor antibody in subacute autonomic neuropathy and cancer-related syndromes', Neurology, vol. 50, no. 6, pp. 1806-1813.
Vernino, Steven ; Adamski, Jill ; Kryzer, Thomas J. ; Fealey, Robert D. ; Lennon, Vanda A. / Neuronal nicotinic ACH receptor antibody in subacute autonomic neuropathy and cancer-related syndromes. In: Neurology. 1998 ; Vol. 50, No. 6. pp. 1806-1813.
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