Which autoimmune disease is mediated by antibodies against the acetylcholine receptor at the neuromuscular junction?

• A. Myasthenia gravis
• B. Lambert-Eaton syndrome
• C. Multiple Sclerosis
• D. Guillain-Barré syndrome

Answer: (A)

Autoantibodies against the nicotinic acetylcholine receptor at the neuromuscular junction cause myasthenia gravis. When these antibodies bind the receptors, they promote receptor internalization and activate complement, reducing the number of functional ACh receptors on the postsynaptic membrane. With fewer receptors, the end-plate potential is less likely to reach threshold, so muscle fibers fail to fire reliably, especially with repeated use. That produces the hallmark pattern of fatigable weakness, often starting with ptosis and diplopia and progressing to proximal muscle weakness. Symptoms typically vary throughout the day and improve with rest; they also respond to acetylcholinesterase inhibitors that increase acetylcholine availability at the junction and to immunomodulatory therapies, with a frequent association to thymic abnormalities.

For context, the other conditions involve different mechanisms: Lambert-Eaton syndrome features antibodies against presynaptic calcium channels, reducing acetylcholine release and sometimes showing improvement with activity; multiple sclerosis is a CNS demyelinating disease; Guillain-Barré syndrome is an autoimmune peripheral neuropathy affecting nerve myelin or axons.