Passive transfer of autoimmune autonomic neuropathy to mice

Steven Vernino, Leonid G. Ermilov, Lei Sha, Joseph H. Szurszewski, Phillip Anson Low, Vanda A Lennon

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Autoimmune autonomic neuropathy (AAN) is an acquired, often severe, form of dysautonomia. Many patients with AAN have serum antibodies specific for the neuronal ganglionic nicotinic acetylcholine receptor (AChR). Rabbits immunized with a fusion protein corresponding to the N-terminal extracellular domain of the ganglionic AChR α3 subunit produce ganglionic AChR antibodies and develop signs of experimental AAN (EAAN) that recapitulate the cardinal autonomic features of AAN in man. We now demonstrate that EAAN is an antibody-mediated disorder by documenting sympathetic, parasympathetic, and enteric autonomic dysfunction in mice injected with rabbit IgG containing ganglionic AChR antibodies. Recipient mice develop transient gastrointestinal dysmotility, urinary retention, dilated pupils, reduced heart rate variability, and impaired catecholamine response to stress. The autonomic signs are associatedm with a reversible failure of nicotinic cholinergic synaptic transmission in superior mesenteric ganglia. Mice injected with IgG from two patients with AAN (of three tested) demonstrated a milder phenotype with evidence of urinary retention and gastrointestinal dysmotility. The demonstration that ganglionic AChR-specific IgG causes impaired autonomic synaptic transmission and autonomic failure in mice implicates an antibody-mediated pathogenesis for AAN. The antibody effect is potentially reversible, justifying early use of immunomodulatory therapy directed at lowering IgG levels and abrogating IgG production in patients with AAN.

Original languageEnglish (US)
Pages (from-to)7037-7042
Number of pages6
JournalJournal of Neuroscience
Volume24
Issue number32
DOIs
StatePublished - Aug 11 2004

Fingerprint

Cholinergic Receptors
Immunoglobulin G
Antibodies
Urinary Retention
Synaptic Transmission
Experimental Autoimmune Neuritis
Primary Dysautonomias
Rabbits
Immunomodulation
Nicotinic Receptors
Pupil
Ganglia
Cholinergic Agents
Catecholamines
Heart Rate
Phenotype
Serum
Proteins

Keywords

  • Electrophysiology
  • Gastrointestinal dysmotility
  • Neuronal nicotinic acetylcholine receptor
  • Parasympathetic
  • Pupil
  • Sympathetic

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Passive transfer of autoimmune autonomic neuropathy to mice. / Vernino, Steven; Ermilov, Leonid G.; Sha, Lei; Szurszewski, Joseph H.; Low, Phillip Anson; Lennon, Vanda A.

In: Journal of Neuroscience, Vol. 24, No. 32, 11.08.2004, p. 7037-7042.

Research output: Contribution to journalArticle

Vernino, Steven ; Ermilov, Leonid G. ; Sha, Lei ; Szurszewski, Joseph H. ; Low, Phillip Anson ; Lennon, Vanda A. / Passive transfer of autoimmune autonomic neuropathy to mice. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 32. pp. 7037-7042.
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