Autoimmune Autonomic Neuropathy

Acetylcholine is one of many neurotransmitters in the autonomic nervous system.

Acetylcholine receptors are subdivided into muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors, while the nicotinic acetylcholine receptors are ligand-gated ion channels. There are 5 muscarinic receptors and 17 nicotinic acetylcholine receptors .

One of these receptors, ganglionic (α3) acetylcholine receptor (AChR), is a target for auto antibodies resulting in autonomic dysfunction.

Autonomic dysfunction associated with ganglionic antibody is called autoimmune autonomic ganglionopathy (AAG), but has been replaced by the term autoimmune autonomic neuropathy (AAN).

Autoimmune autonomic neuropathy is mentioned as new diagnosis in ICD11 Beta Draft:

7N36.1 Autoimmune autonomic neuropathy, ganglionic acetylcholine receptor antibody positive

7N37.1 Limited autoimmune autonomic neuropathy: ganglionic acetylcholine receptor antibody positive

Lower G-AchR antibodies titers are often associated with either subacute-chronic variants of autonomic neuropathy or limited forms of autonomic neuropathy. Reference: Other autonomic neuropathies associated with ganglionic antibody

Autoimmune autonomic ganglionopathy is a clinically heterogeneous disease with variable presentation, particularly in subjects with lower antibody titers. Reference: Antibody titers predict clinical features of autoimmune autonomic ganglionopathy

Patients with primary autonomic neuropathies might manifest restricted forms of autonomic dysfunctions, such as cholinergic dysautonomia, postural orthostatic tachycardia syndrome and diffuse sympathetic and parasympathetic dysfunctions. Orthostatic symptoms are common, and they can be accompanied by syncope. Chronic progression is possible. Reference: Wide range of clinicopathological features in immune-mediated autonomic neuropathies

Reversible cognitive impairment is independently associated with both orthostatic hypotension and elevated nicotinic acetylcholine receptor autoantibodies, thereby expanding the clinical spectrum of autonomic ganglionopathy and, in so doing, providing an additional treatable cause of cognitive impairment. Reference: Autoimmune autonomic ganglionopathy with reversible cognitive impairment


More articles on the subject:

Postural orthostatic tachycardia syndrome: the Mayo clinic experience

Treatment-responsive pandysautonomia in an adolescent with ganglionic α3-AChR antibodies

Autoantibody-induced internalization of nicotinic acetylcholine receptor α3 subunit exogenously expressed in human embryonic kidney cells

Gastrointestinal hypomotility with loss of enteric nicotinic acetylcholine receptors: active immunization model in mice

Sudomotor dysfunction in autoimmune autonomic ganglionopathy

Efficacy of immunotherapy in seropositive and seronegative putative autoimmune autonomic ganglionopathy

Ganglionic acetylcholine receptor autoantibody: oncological, neurological, and serological accompaniments

Autonomic ganglia, acetylcholine receptor antibodies, and autoimmune ganglionopathy

Passive Transfer of Autoimmune Autonomic Neuropathy to Mice

Ganglionic Acetylcholine Receptor Autoantibody:Oncological, Neurological, and Serological Accompaniments

Autonomic Involvement in Subacute and Chronic Immune-Mediated Neuropathies