Myasthenia gravis (MG) is a neuromuscular autoimmune disorder. It occurs when a person’s immune system mistakenly attacks their muscles. This leads to muscle fatigue and weakness, which worsens with exercise and improves with rest.

Antibodies as cause of MG

Myasthenia gravis is caused by problems in the transmission of nerve impulses to muscles. It occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction — the place where nerve cells end and connect with the muscles they control.

Normally when impulses travel down the nerve, the nerve endings release a chemical called acetylcholine. Acetylcholine travels from the nerve ending and binds to acetylcholine receptors on the surface of the muscle cells, which are activated and generate a muscle contraction.

The body’s immune system produces antibodies that normally help fight off infections and threats. In MG patients, the antibodies mistakenly block, alter, or destroy the receptors for acetylcholine at the neuromuscular junction. With fewer working receptor sites available, the muscles cannot contract properly, and easily become tired and weak.

MG is caused mostly by antibodies attacking the acetylcholine receptor itself. However, antibodies to MuSK (Muscle-Specific Kinase) protein, also can lead to impaired signal transmission at the neuromuscular junction.

Thymus gland

The precise origin of the autoimmune response in MG is not known, but researchers believe that abnormalities of the thymus gland, a part of the immune system, almost certainly plays a part.

Research has shown that in most cases, MG patients have increased numbers of cells in the thymus and about 10-15 percent of affected individuals have thymomas (tumors) in the thymus. Researchers suggest that the thymus of an MG patient may trigger or maintain the production of the antibodies that block the transmission of nerve signals.

The abnormalities that lead to the production of anti-MuSK antibodies is poorly understood and appears not to involve the thymus.

Other causes of MG

Most individuals with MG have no family history and the disorder seems to occur spontaneously. However, 3 to 5 percent of patients may have a amily member with MG or other autoimmune disorders, but the inheritance pattern is unknown.

There also is a distinct type of myasthenia called congenital myasthenic syndrome. In this rare and hereditary form of myasthenia, the muscle weakness typically begins in early childhood, but also may appear in adolescence or adulthood. The condition is caused by a genetic mutation and not by an autoimmune response.

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