Causes of Myasthenia Gravis

Myasthenia gravis (MG) is a neuromuscular autoimmune disorder. It occurs when a person’s immune system mistakenly attacks certain proteins that play a key role in nerve-muscle communication. This leads to muscle fatigue and weakness, which worsens with exercise and improves with rest.

Self-reactive antibodies

MG is caused by problems in the transmission of nerve impulses to muscles. It occurs when normal communication between nerves and muscles is interrupted at the neuromuscular junction — the place where nerve cells come into contact with the muscles they control.

Normally when impulses travel down a nerve, nerve endings release a chemical called acetylcholine. Acetylcholine travels from nerve endings and binds to acetylcholine receptors (AChRs) located on the surface of muscle cells, in order to promote muscle contraction.

The body’s immune system normally produces antibodies that help fight off infections and threats. In MG patients, however, the immune system produces self-reactive antibodies that mistakenly block, alter, or destroy AChRs at the neuromuscular junction. With fewer working receptors available, muscles lose their ability to contract properly and progressively weaken.

MG is caused mostly by antibodies targeting the AChR itself. However, antibodies directed against the muscle-specific kinase (MuSK) protein, can also lead to impaired signal transmission at the neuromuscular junction. Yet, around 10%–15% of patients have double-seronegative MG, meaning that neither AChR nor MuSk self-reactive antibodies can be found circulating in their bloodstream.

In recent years, researchers have discovered two self-reactive antibodies targeting the proteins agrin and low-density lipoprotein receptor-related protein 4 in patients with double-seronegative MG. These proteins are key for the formation and maintenance of neuromuscular junctions. As such, self-reactive antibodies targeting these proteins are likely to cause MG in these patients.

Thymus gland abnormalities

The precise origin of the autoimmune response in MG is not known, but researchers believe that abnormalities of the thymus gland, an organ that is part of the immune system, play a role.

Research has shown that in most cases, MG patients have an enlarged thymus — a condition known as thymus hyperplasia — caused by an increased number of cells within the organ. Moreover, about 10%–15% of patients have tumors in the thymus called thymomas, which are usually benign. Researchers believe that in MG patients, the thymus may trigger or help maintain the production of the harmful self-reactive antibodies that drive the disease.

Nevertheless, abnormalities leading to the production of anti-MuSK antibodies are poorly understood and appear not to involve the thymus.

Other causes

Most individuals with MG have no family history, and the disorder seems to occur spontaneously. However, 3%–5% of patients may have family members with MG or other autoimmune disorders, but the inheritance pattern is unclear.

In rare cases, children of mothers with MG may be born with transient neonatal MG, but most of them recover after receiving adequate treatment following birth.

There also is a rare and hereditary form called congenital MG. This type is caused by genetic mutations in genes involved in nerve-muscle communication and is not driven by an autoimmune response. Patients with this form of MG typically start experiencing muscle weakness in early childhood, although this may also happen later in life.


Last updated: July 27, 2021


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2021 Myasthenia Gravis Survey Results

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Myasthenia Gravis News conducted a survey from Feb. 11-March 28 to gain greater insight into the characteristics of the MG community and disease management. Results of the survey have now been published. Click on the image to view the infographic, and click here to read the story.