Autoimmune autonomic ganglionopathy: Ganglionic acetylcholine receptor autoantibodies

Autoimmune Autonomic Ganglionopathy (AAG) is a rare immune-mediated disease of the autonomic nervous system. The incidence of AAG is unknown and diagnosis is often difficult due to the multicompartmental nature of the autonomic nervous system - sympathetic, parasympathetic and enteric components - with variable severity and number of components affected. Diagnostic confidence is increased when ganglionic acetylcholine receptor (gnACHR) autoantibodies are detected. Three gnACHR autoantibody diagnostic assays have been described (two binding assays, one receptor immunomodulation assay), but cross-validation between assays is limited. The prevalence of gnACHR autoantibodies in AAG is not known, with application of different clinical and laboratory criteria in the few studies of AAG cohorts and large retrospective laboratory studies of positive gnACHR autoantibodies lacking adequate clinical characterisation. Furthermore, the rate of unexpected gnACHR autoantibody positivity in conditions without overt autonomic dysfunction (false positive results) adds to the complexity of their interpretation. We review the pathophysiology of gnACHR autoantibodies and assays for their detection, with immunomodulation and high titer radioimmunoprecipitation results likely offering better AAG disease identification.