TY - GEN
T1 - Neuronal acetylcholine receptor autoimmunity
AU - Vernino, Steven
PY - 2008/6
Y1 - 2008/6
N2 - Nicotinic acetylcholine receptors (AChRs) are ligand-gated cation channels that are present throughout the nervous system. The muscle AChR mediates transmission at the neuromuscular junction; antibodies against the muscle AChR are the cause of myasthenia gravis. There are numerous subtypes of AChRs present throughout the nervous system. These neuronal AChRs are closely related to the muscle AChR structurally, but are pharmacologically and immunologically distinct. The ganglionic (α3-type) neuronal AChR mediates fast synaptic transmission in sympathetic, parasympathetic, and enteric autonomic ganglia. Ganglionic AChR antibodies are found in up to 50% of patients with autoimmune autonomic ganglionopathy (AAG). Patients with AAG present with severe autonomic failure. Major clinical features include orthostatic hypotension, gastrointestinal dysmotility, anhidrosis, bladder dysfunction, and sicca symptoms. Impaired pupillary light reflex is often seen. Like myasthenia, AAG is an antibody-mediated neurological disorder. Patients may improve with plasma exchange treatment or other immunomodulatory treatment. Experimental AAG, which recapitulates many of the features of the human disease, can be induced in rabbits by immunization against the ganglionic AChR or by passive transfer of antibodies to mice. Ganglionic AChR IgG inhibits nicotinic membrane current in cultured neuroblastoma cells. Central nervous system neuronal AChRs may also be targets of autoimmunity. For example, antibodies against α7-type AChRs have been identified in a few patients with encephalitis. It is still unclear if antibodies against receptors in the central nervous system can directly cause disease.
AB - Nicotinic acetylcholine receptors (AChRs) are ligand-gated cation channels that are present throughout the nervous system. The muscle AChR mediates transmission at the neuromuscular junction; antibodies against the muscle AChR are the cause of myasthenia gravis. There are numerous subtypes of AChRs present throughout the nervous system. These neuronal AChRs are closely related to the muscle AChR structurally, but are pharmacologically and immunologically distinct. The ganglionic (α3-type) neuronal AChR mediates fast synaptic transmission in sympathetic, parasympathetic, and enteric autonomic ganglia. Ganglionic AChR antibodies are found in up to 50% of patients with autoimmune autonomic ganglionopathy (AAG). Patients with AAG present with severe autonomic failure. Major clinical features include orthostatic hypotension, gastrointestinal dysmotility, anhidrosis, bladder dysfunction, and sicca symptoms. Impaired pupillary light reflex is often seen. Like myasthenia, AAG is an antibody-mediated neurological disorder. Patients may improve with plasma exchange treatment or other immunomodulatory treatment. Experimental AAG, which recapitulates many of the features of the human disease, can be induced in rabbits by immunization against the ganglionic AChR or by passive transfer of antibodies to mice. Ganglionic AChR IgG inhibits nicotinic membrane current in cultured neuroblastoma cells. Central nervous system neuronal AChRs may also be targets of autoimmunity. For example, antibodies against α7-type AChRs have been identified in a few patients with encephalitis. It is still unclear if antibodies against receptors in the central nervous system can directly cause disease.
KW - Autonomic neuropathy
KW - Gastrointestinal dysmotility
KW - Orthostatic hypotension
KW - Thymoma
UR - http://www.scopus.com/inward/record.url?scp=45249092801&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=45249092801&partnerID=8YFLogxK
U2 - 10.1196/annals.1405.011
DO - 10.1196/annals.1405.011
M3 - Conference contribution
C2 - 18567861
AN - SCOPUS:45249092801
SN - 9781573316873
T3 - Annals of the New York Academy of Sciences
SP - 124
EP - 128
BT - Myasthenia Gravis and Related Disorders 11th International Conference
PB - Blackwell Publishing Inc.
ER -