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Autoimmune autonomic ganglionopathy: IgG effects on ganglionic acetylcholine receptor current

Item Type:Article
Title:Autoimmune autonomic ganglionopathy: IgG effects on ganglionic acetylcholine receptor current
Creators Name:Wang, Z. and Lowden, P.A. and Jordan, J. and Freeman, R. and Gibbons, C.H. and Schroeder, C. and Sandroni, P. and Vernino, S.
Abstract:Background: Autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated form of diffuse autonomic failure. Many patients have serum antibodies that bind to the ganglionic acetylcholine receptors (AChRs) that mediate fast synaptic transmission in autonomic ganglia. Previous clinical studies and observations in animal models suggest that AAG is an antibody-mediated neurologic disorder. Methods: Using whole-cell patch clamp techniques, we recorded ganglionic AChR currents in cultured human IMR-32 cells and examined the effects of bath application of IgG derived from patients with AAG. Results: IgG from seven patients with AAG all produced a progressive decline in whole-cell ganglionic AChR current, whereas IgG from control subjects had no effect. The effect was abolished at low temperature. Fab antibody fragments had no effect unless a secondary antibody was added concurrently. IgG from one patient also produced a more immediate reduction of ganglionic AChR current. Conclusions: The characteristics of antibody-mediated inhibition of ganglionic acetylcholine receptor (AChR) current are consistent with modulation and blocking of the membrane AChR, analogous to the effects of muscle AChR antibodies in myasthenia gravis. Our observations demonstrate that antibodies in patients with autoimmune autonomic ganglionopathy (AAG) cause physiologic changes in ganglionic AChR function and confirm that AAG is an antibody-mediated disorder.
Keywords:Autoantibodies, Autoimmune Diseases, Autonomic Nervous System Diseases, Cell Line, Tumor, Ganglia, Immunoglobulin G, Membrane Potentials, Patch-Clamp Techniques, Receptors, Animals, Rabbits
Publisher:American Academy of Neurology
Page Range:1917-1921
Date:29 May 2007
Official Publication:https://doi.org/10.1212/01.wnl.0000263185.30294.61
PubMed:View item in PubMed

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