Autoimmune autonomic ganglionopathy

Abstract

Autoimmune autonomic ganglionopathy (AAG) is a rare disorder of antibody-mediated impairment of transmission across the autonomic ganglia resulting in severe autonomic failure, in which autoantibodies to ganglionic nicotinic acetylcholine receptors (gAChRs) may play a central role. Here, we developed luciferase immunoprecipitation systems (LIPS) to diagnose AAG based on immunoglobulin G antibodies 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 anti-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 and central nervous system involvement as an occasional complication of AAG. Our results demonstrated that the LIPS assay is a useful novel tool for detecting autoantibodies against gAChR in patients with AAG.