Autonomic ganglia, acetylcholine receptor antibodies, and autoimmune ganglionopathy

Abstract

Nicotinic acetylcholine receptors (AChR) are ligand-gated cation channels that are present throughout the nervous system. The ganglionic (α3-type) neuronal AChR mediates fast synaptic transmission in sympathetic, parasympathetic and enteric autonomic ganglia. Autonomic ganglia are an important site of neural integration and regulation of autonomic reflexes. Impaired cholinergic ganglionic synaptic transmission is one important cause of autonomic failure. Ganglionic AChR antibodies are found in many patients with autoimmune autonomic ganglionopathy (AAG). These antibodies recognize the α3 subunit of the ganglionic AChR, and thus do not bind non-specifically to other nicotinic AChR. Patients with high levels of ganglionic AChR antibodies typically present with rapid onset of severe autonomic failure, with orthostatic hypotension, gastrointestinal dysmotility, anhidrosis, bladder dysfunction and sicca symptoms. Impaired pupillary light reflex is often seen. Like myasthenia gravis, AAG is an antibody-mediated neurological disorder. Antibodies from patients with AAG inhibit ganglionic AChR currents and impair transmission in autonomic ganglia. An animal model of AAG in the rabbit recapitulates the important clinical features of the human disease and provides additional evidence that AAG is an antibody-mediated disorder caused by impairment of synaptic transmission in autonomic ganglia.

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.…”

Autoimmune autonomic ganglionopathy manifesting as acute-onset orthostatic hypotension in a patient undergoing peritoneal dialysis

“…In the present case, the patient had autonomic neuropathy with superficial light sense impairment, although movement impairment was not involved. In this regard, AASN and GBS should be considered in the differential diagnosis because they can both show autonomic and sensory impairment [9]. Although the presence of an antecedent event, the monophasic nature of the clinical course, and ganglionopathy are shared in AAG and AASN, the presence of obvious sensory involvement and the positive titers of anti-gAChR antibodies strongly indicate AAG, rather than AASN [4].…”

“…The clinical features of AAG reflect impairment in sympathetic (orthostatic hypotension, anhidrosis), parasympathetic (reduced lacrimation, salivation, and pupil constriction), and enteric functions (ileus, abdominal colic, diarrhea, and constipation). The combination of tonic pupils and gastrointestinal dysmotility in the setting of severe orthostatic hypotension is particularly suggestive of AAG [9].…”

“…Up to 50 % of patients with the acute or subacute form of this disorder have high levels of autoantibodies that bind to gAChR [9]. As gAChR is located only in the sympathetic, parasympathetic, and enteric autonomic ganglia, AAG is considered to show autonomic dysfunction without sensory and motor impairment [4].…”

Abelson Family Tyrosine Kinases Regulate the Function of Nicotinic Acetylcholine Receptors and Nicotinic Synapses on Autonomic Neurons

“…Consistent with their diversity and widespread distribution, nAChRs are involved in several neurological disorders. Autonomic ganglia feature nAChRs assembled from ␣7 subunits (␣7-nAChRs) and from ␣3, ␤4, ␣5 Ϯ ␤2 subunits (␣3*-nAChRs) (Margiotta and Pugh, 2004), and a constellation of ganglionopathies are associated with the presence of ␣3 subunit autoantibodies that impair receptor function and synaptic transmission (Vernino et al, 2009). In brain, nAChRs containing ␣4 and ␤2 subunits (␣4␤2-nAChRs) have been in implicated in Alzheimer's disease, Parkinson's disease, and schizophrenia (Newhouse and Kelton, 2000).…”