Potassium channel complex autoimmunity induced by inhaled brain tissue aerosol

Jeffrey W. Meeusen, Christopher J. Klein, Istvan Pirko, Keegan E. Haselkorn, Thomas J. Kryzer, Sean J. Pittock, Daniel H. Lachance, P. James Dyck, Vanda A. Lennon

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Objective: To test the hypothesis that autoimmunity induced by inhalation of aerosolized brain tissue caused outbreaks of sensory-predominant polyradiculoneuropathy among swine abattoir employees in the Midwestern United States. Methods: Mice were exposed intranasally, 5 days per week, to liquefied brain tissue. Serum from exposed mice, patients, and unaffected abattoir employees were analyzed for clinically pertinent neural autoantibodies. Results: Patients, coworkers, and mice exposed to liquefied brain tissue had an autoantibody profile dominated by neural cation channel immunoglobulin Gs (IgGs). The most compelling link between patients and exposed mice was magnetic resonance imaging (MRI) evidence of grossly swollen spinal nerve roots. Autoantibody responses in patients and mice were dose-dependent and declined after antigen exposure ceased. Autoantibodies detected most frequently, and at high levels, bound to detergent-solubilized macromolecular complexes containing neuronal voltage-gated potassium channels ligated with a high affinity Kv1 channel antagonist, 125I-α-dendrotoxin. Exposed mice exhibited a behavioral phenotype consistent with potassium channel dysfunction recognized in drosophila with mutant ("shaker") channels: reduced sensitivity to isoflurane-induced anesthesia. Pathological and electrophysiological findings in patients supported peripheral nerve hyperexcitability over destructive axonal loss. The pain-predominant symptoms were consistent with sensory nerve hyperexcitability. Interpretation: Our observations establish that inhaled neural antigens readily induce neurological autoimmunity and identify voltage-gated potassium channel complexes as a major immunogen.

Original languageEnglish (US)
Pages (from-to)417-426
Number of pages10
JournalAnnals of neurology
Volume71
Issue number3
DOIs
StatePublished - Mar 2012

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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