A functional autoantibody in narcolepsy.
Narcolepsy is widely believed to have an autoimmune basis, but conventional immunological approaches have failed to detect a serum autoantibody marker. Since cholinergic hyperactivity is a feature of narcolepsy-cataplexy, we transferred IgG from nine patients with narcolepsy and nine healthy controls to mice and assessed the effect on smooth muscle contractile responses to cholinergic stimulation. IgG from all narcolepsy patients significantly enhanced bladder contractile responses to the muscarinic agonist carbachol and to neuronally released acetylcholine compared with control IgG (p<0.0001), whereas contraction of the sympathetically innervated vas deferens was unaltered. Our findings provide direct evidence for the autoimmune hypothesis of narcolepsy.
Smith
Anthony J F
AJ
Department of Immunology, Allergy and Arthritis, Flinders Medical Centre, Bedford Park, SA 5042, Australia.
Jackson
Michael W
MW
Neufing
Petra
P
McEvoy
R D
RD
Gordon
Tom P
TP
D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000032:analysis* / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D005260:Female; D006683:HLA-DQ Antigens / Q000032:analysis; D059866:HLA-DQ beta-Chains; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology; D009290:Narcolepsy / Q000175:diagnosis / Q000276:immunology*; D010275:Parasympathetic Nervous System / Q000502:physiology; D009435:Synaptic Transmission
D001323:Autoantibodies; D018679:Cholinergic Agonists; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D002217:Carbachol