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NEUROLOGY 2007;68:1917-1921
© 2007 American Academy of Neurology

Autoimmune autonomic ganglionopathy

IgG effects on ganglionic acetylcholine receptor current

Z. Wang, MD, P. A. Low, MD, J. Jordan, MD, R. Freeman, MD, C. H. Gibbons, MD, C. Schroeder, MD, P. Sandroni, MD and S. Vernino, MD, PhD

From the Department of Neurology (Z.W., S.V.), University of Texas Southwestern Medical Center, Dallas, Department of Neurology (P.A.L., P.S.), Mayo Clinic College of Medicine, Rochester, MN, and Department of Neurology (R.F., C.H.G.), Beth Israel Deaconess Medical Center, Boston, MA; and Medical University Charité (J.J., C.S.), Franz Volhard Clinical Research Center, Max Delbrück Center for Molecular Medicine, HELIOS Klinikum, Berlin, Germany.

Address correspondence and reprint requests to Dr. S. Vernino, UT Southwestern Department of Neurology, 5323 Harry Hines Blvd., Dallas, TX 75390-9036 steven.vernino{at}utsouthwestern.edu

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.

Supported by NIH grants NS32352 (P.A.L., S.V.), NS48077 (S.V.), and DK68055 (S.V.).

Disclosure: The authors report no conflicts of interest.

Received September 29, 2006. Accepted in final form January 31, 2007.




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S. Vernino, P. Sandroni, W. Singer, and P. A. Low
Invited Article: Autonomic ganglia: Target and novel therapeutic tool
Neurology, May 13, 2008; 70(20): 1926 - 1932.
[Abstract] [Full Text] [PDF]


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