Acetylcholine Receptor (AChR)-modulating Antibodies

Diagnose myasthenia gravis (MG); monitor response to treatment of myasthenia gravis.

False positives can occur in patients with serum drawn within 48 hours of administration of general anesthesia and muscle relaxants. Antibodies to a-bungarotoxin (a-BTX) may sometimes be found in patients treated with snake venom. Recently administered radioisotopes may interfere with the assay in unpredictable ways. Acetylcholine receptor autoantibodies are not typically found in congenital myasthenia gravis.

Myasthenia gravis is an autoimmune disorder manifested by muscle weakness caused by the loss or dysfunction of acetylcholine receptors (AChR) of skeletal muscle. Autoantibodies (binding, blocking, and/or modulating) to postsynaptic AChRs are detectable in the serum of 90% of patients with generalized MG and in 55% to 70% of patients with ocular myasthenia. These autoantibodies interfere with normal neuromuscular function, causing muscle weakness and fatigue. Receptor antibody levels tend to rise several weeks before symptoms increase in patients with established MG. Remission after thymectomy is associated with a progressive decline in antibody levels. Consequently, measurements of AChR antibodies can be used in monitoring disease progression as well as the effects of treatment. Modulating antibodies are responsible for the degradation of AChR at the muscle cell surface. Modulating antibodies bind to two receptor molecules on the cell surface and accelerate internalization, triggering endocytosis and degradation. The relative increase in this degradation rate closely corresponds to the disease severity.

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