Causes of myasthenia gravis

Last updated Dec. 19, 2024, by Lindsey Shapiro, PhD
Fact-checked by Joana Carvalho, PhD

Myasthenia gravis (MG) is a neuromuscular disease that has an autoimmune origin, meaning it’s caused by a mistaken attack by the body’s immune system. Self-reactive antibodies produced by the immune system are at the forefront of this attack, which affects the function of the neuromuscular junction — the region where nerve and muscle cells communicate to coordinate voluntary movements.

The disorder leads to symptoms of muscle weakness and fatigue that worsen with exercise and improve with rest. There are several types of MG.

It isn’t always clear why the self-reactive antibodies in MG arise, but their production has been linked to abnormalities in the thymus gland, an organ that’s part of the immune system. MG is caused by the immune system’s attack on various components of the neuromuscular junction.

Self-reactive antibodies

For proper communication to occur at the neuromuscular junction, nerve cells release a chemical called acetylcholine that travels to the surface of a muscle cell. There it binds to acetylcholine receptors, known as AChRs, to elicit muscle contraction.

Although antibodies normally serve to protect the body against infections, in autoimmune diseases, the immune system wrongfully produces self-reactive antibodies or autoantibodies, that target the body’s own healthy tissues.

The most common cause of MG is the production of autoantibodies that target AChRs at the neuromuscular junction, which occurs in about 85% of patients. When there is an insufficient number of receptors available for acetylcholine to bind to, muscles lose their ability to contract properly, leading to progressive muscle weakness and fatigue.

In about 6% of patients, antibodies targeting muscle-specific kinase or MuSK — another protein important for the function of the neuromuscular junction — are present, which are thought to be the cause of MG for those individuals.

About 10% of patients have double-seronegative myasthenia gravis, meaning neither AChR nor MuSK autoantibodies can be found in their bloodstream.

More recent research has identified that, in such cases, there may be antibodies against other proteins important for the formation and maintenance of the neuromuscular junction that are causing the disease, such as those targeting agrin or low-density lipoprotein receptor-related protein 4 (LRP4). The lack of self-reactive antibodies in seronegative patients may also be explained by the tests’ inability to detect them.

Thymus gland abnormalities

While the production of autoantibodies is known to drive myasthenia gravis symptoms, their precise origin is not well established. Researchers believe abnormalities in the thymus gland may play a role.

Located in the chest between the lungs, the thymus gland is a component of the immune system that works to produce white blood cells that fight off infection. Early in life, the thymus is very active and produces a lot of immune cells, but its function gradually diminishes as a person gets older and other immune organs take over.

About 70% of MG patients have thymic hyperplasia, a condition wherein the thymus is enlarged due to an increased number of cells in the organ, which indicates an overly active immune response. Moreover, about 10%-15% of patients have tumors in the thymus called thymomas, which normally grow slowly and don’t tend to spread to other organs, but may still affect the gland’s function.

Given that, researchers believe the thymus may trigger or help maintain the production of the harmful self-reactive antibodies that drive MG. This particularly is thought to be the case among patients with antibodies targeting AChRs. Abnormalities leading to the production of anti-MuSK or other types of antibodies are poorly understood and seem not to involve the thymus.

Other causes

Most people living with MG have no family history of the disorder; it seems to occur spontaneously. While 3%-5% of patients have family members with MG or other autoimmune conditions, the inheritance pattern remains unclear. Some studies have suggested that certain genetic factors may increase a person’s susceptibility to developing MG. These include specific genetic variations in genes that encode human leukocyte antigen (HLA) cell surface proteins, which play a key role in immune system regulation.

About 10%-20% of babies born to mothers with MG will develop a temporary form of the disease called transient neonatal MG. That can happen because, during pregnancy, a mother’s autoantibodies may be transferred to her unborn child through the placenta. In most cases, babies with this form of MG will naturally recover in the weeks after birth, as their own antibodies replace their mother’s.

Some people have mutations in genes involved in nerve-muscle communication, and thus develop symptoms similar to those of MG that are not caused by an autoimmune response. These genetic conditions fall under the umbrella term of congenital myasthenia or congenital myasthenic syndrome (CMS). Despite the similarities, CMS and MG are considered to be different disease entities, each with distinct underlying causes and requiring different types of treatment.

Myasthenia Gravis News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.