Clinical Features of Autoimmune Autonomic Ganglionopathy and the Detection of Subunit-Specific Autoantibodies to the Ganglionic Acetylcholine Receptor in Japanese Patients

Abstract

Autoimmune autonomic ganglionopathy (AAG) is a rare acquired channelopathy that is characterized by pandysautonomia, in which autoantibodies to ganglionic nicotinic acetylcholine receptors (gAChR) may play a central role. Radioimmunoprecipitation (RIP) assays have been used for the sensitive detection of autoantibodies to gAChR in the serum of patients with AAG. Here, we developed luciferase immunoprecipitation systems (LIPS) to diagnose AAG based on IgGs to both the α3 and β4 gAChR subunits in patient serum. We reviewed the serological and clinical data of 50 Japanese patients who were diagnosed with AAG. With the LIPS testing, we detected anti-α3 and -β4 gAChR antibodies in 48% (24/50) of the patients. A gradual mode of onset was more common in the seropositive group than in the seronegative group. Patients with AAG frequently have orthostatic hypotension and upper and lower gastrointestinal tract symptoms, with or without anti-gAChR. The occurrence of autonomic symptoms was not significantly different between the seropositive and seronegative group, with the exception of achalasia in three patients from the seropositive group. In addition, we found a significant overrepresentation of autoimmune diseases in the seropositive group and endocrinological abnormalities as an occasional complication of AAG. Our results demonstrated that the LIPS assay was a useful novel tool for detecting autoantibodies against gAChR in patients with AAG.

Autoimmune postural orthostatic tachycardia syndrome

“…We queried the presence or absence of each of the following functions that are controlled by the autonomic system as reported in our previous study: syncope or orthostatic hypotension (OH) for orthostatic intolerance (OI); arrhythmia; pupillary dysfunction; sicca complex; coughing episodes; skin dryness or hypohidrosis/anhidrosis for heat intolerance; upper GI system problems; diarrhea or constipation indicating dysfunction of the lower GI system; dysuria or urinary retention needing catheterization for bladder dysfunction; and sexual dysfunction 11. For the all patients, questionnaires were sent to the referring neurologists.…”

“…Sandroni and Low demonstrated occasional positivity to gAChR antibodies in POTS patients 10. Previously, we reported the relationship among the anti‐gAChR antibodies, autonomic dysfunction, and autoimmune rheumatic diseases 11, 12, 13. We attempted to elucidate the autoimmune pathophysiology of POTS in this study as a part of our comprehensive approach.…”

“…Serum gAChR α 3 and β 4 antibodies were detected using Luciferase immunoprecipitation system (LIPS) assays, as described previously 11. Antibody levels were expressed as the antibody index (A.I.).…”

Acquired anhidrosis in a case of autoimmune autonomic ganglionopathy

“…AAG with ganglionic nicotinic acetylcholine receptor (gnAChR) antibodies, which block transmission at autonomic ganglia, delay the peak of symptoms relating to autonomic neuropathies and are associated with other autoimmune diseases compared with AAG without those antibodies. [2][3][4] To date, detailed descriptions regarding the dysregulation of sweating in AAG are limited. 5 Here, we present a case of an acquired anhidrosis in AAG.…”

“…AAG is characterized by gnAChR antibody reactivity, but a substantial percentage of AAG patients are seronegative for gnAChR antibodies. 4 In our case, we considered AAG due to an acute onset of orthostatic hypotension, constipation, impotence and dysuria in addition to anhidrosis. A decreased accumulation and increased washout rate by MIBG indicated lower distribution and function of cardiac sympathetic nerves.…”