Passive transfer of autoimmune autonomic neuropathy to mice

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

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


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
Issue number32
StatePublished - Aug 11 2004


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

ASJC Scopus subject areas

  • General Neuroscience


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