Experimental autoimmune autonomic neuropathy

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Antibodies specific for the neuronal ganglionic nicotinic acetylcholine receptor (nAChR) are found in high titer in serum of patients with subacute autonomic failure. This clinical disorder is known as autoimmune autonomic neuropathy (AAN). Rabbits immunized with a neuronal nAChR α3 subunit fusion protein produce ganglionic nAChR antibodies and develop autonomic failure (experimental AAN, or EAAN). We used quantitative measures of autonomic function to demonstrate that this animal model of neuronal nAChR autoimmunity recapitulates the cardinal autonomic features of AAN in humans. The severity of dysautonomia in the rabbit ranges from isolated cardiovagal impairment to severe panautonomic failure with fixed mydriasis, gastroparesis, dry eyes, impaired heart rate variability, hypotension, and low plasma catecholamines. The severity of autonomic failure correlates with serum antibody levels. Immunohistochemical staining of superior cervical ganglia and myenteric plexus neurons demonstrates intact presynaptic nerve terminals and intact postsynaptic neurons containing cytoplasmic nAChR, but lacking surface nAChR. These findings define the autonomic physiology and histopathology of this novel animal model and support the concept that AAN in humans is a disorder of ganglionic cholinergic synaptic transmission caused by ganglionic nAChR antibodies.

Original languageEnglish (US)
Pages (from-to)2053-2059
Number of pages7
JournalJournal of Neurophysiology
Volume90
Issue number3
DOIs
StatePublished - Sep 1 2003

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Experimental Autoimmune Neuritis
Nicotinic Receptors
Antibodies
Cervical Plexus
Animal Models
Primary Dysautonomias
Gastroparesis
Rabbits
Mydriasis
Neurons
Myenteric Plexus
Superior Cervical Ganglion
Presynaptic Terminals
Protein Subunits
Serum
Autoimmunity
Synaptic Transmission
Hypotension
Cholinergic Agents
Catecholamines

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Experimental autoimmune autonomic neuropathy. / Vernino, Steven; Low, Phillip Anson; Lennon, Vanda A.

In: Journal of Neurophysiology, Vol. 90, No. 3, 01.09.2003, p. 2053-2059.

Research output: Contribution to journalArticle

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