Autoimmunity to acetylcholine receptor channels.

Yoshikawa, Hiroaki

Anti‐acetylcholine receptor antibody (AChRAb) targets nicotinic acetylcholine receptors (AChRs) of the neuromuscular junction (NMJ). AChRAb induces degradation of AChRs, which causes a decrease in the efficacy of neuromuscular transmission. The clinical condition induced by this process is myasthenia gravis (MG). Transmission failure at the NMJ is detectable by a repetitive nerve stimulation test. AChRAb may be complicated with thymic abnormalities (thymoma and/or lymphoreticular hyperplasia [LFH]). Moreover, autoimmune thyroid disease may accompany MG. Thymoma and LFH have etiological roles in AChRAb production, and the removal of thymoma and LFH improve MG symptoms. MG therapies, such as acetylcholine esterase inhibitor (AChEI), aim to increase the efficacy of NMJ transmission; however, the effect of AChEI is limited. The primary therapy aims to decrease AChRAb and is combined with thymectomy. There are two methods to remove AChRAb from the patients' blood: (1) reduce the production of immunoglobulins by administration of corticosteroid and/or immunosuppressants and (2) remove immunoglobulin by blood purification. In some patients, long‐lasting immunosuppression is necessary, which causes adverse events. Combinatory use of other immunosuppressants reduces the adverse events of corticosteroids. In addition, intravenous immunoglobulin is available to modify the proportion of immunoglobulin in patients' blood. Recently, humanized monoclonal antibodies against specific molecules have been introduced for immunoglobulin modification; however, they are not AChRAb specific. Thus, it is necessary to consider the safety and cost‐effectiveness of therapies.

CHOLINERGIC receptors; MYASTHENIA gravis; NICOTINIC acetylcholine receptors; AUTOIMMUNITY; NEURAL stimulation; NEUROMUSCULAR transmission; THYROTROPIN receptors; INTRAVENOUS immunoglobulins

Neurology & Clinical Neuroscience, 2024, Vol 12, Issue 3, p143

2049-4173

Academic Journal

10.1111/ncn3.12659