Understanding Myasthenia Gravis Antibodies

Reviewed by: HU Medical Review Board

Myasthenia gravis (MG) is an autoimmune disorder that affects muscles, causing weakness. This weakness often gets worse as the day goes on. Many people first experience these symptoms in their eyes, or ocular muscles. The weakness may stay localized to only the eyes, or it may progress to affect other muscle groups.1

Like many autoimmune disorders, the symptoms of MG are caused by antibodies. Antibodies are proteins made by the immune system to protect your body.1

They typically recognize foreign substances produced by germs, such as bacteria and viruses. They are created every time we are infected with a virus or bacteria and can help our body fight that same or sometimes similar bug faster if we encounter it again.1

The immune system can make mistakes when creating these antibodies. It can create antibodies that signal the immune system to attack healthy tissue. This is what happens in MG.1

What antibodies are involved?

Research shows that 85 percent of people living with MG have antibodies against acetylcholine (ACh) receptors. About 6 percent of people with MG have antibodies against MuSK. Even fewer have antibodies against LRP4.1

However, there are some people who do not show any antibodies when they are tested. Scientists believe this group may have antibodies to molecules that we have not identified yet. In some people, the antibodies that cause MG can be related to a kind of thymus tumor called a thymoma.1

How do they work?

Nerves from the brain send signals to muscles to get them to work. The place where they talk to each other is called the neuromuscular junction. The nerve releases a molecule called ACh. The muscle has ACh receptors that ACh attaches to, causing a signal to the muscle.2

When enough molecules bind to the ACh receptors, the muscle will contract. Both MuSK and LRP4 are proteins involved in this process and required for proper ACh receptor function.2

In MG, the body creates antibodies against 1 of these proteins. In the case of ACh receptor antibodies, there are 2 processes that cause dysfunction of the neuromuscular junction. When the antibody binds to its target on the surface of the muscle cell it:1

  • Causes the ACh receptor to be removed from the surface
  • Triggers an inflammatory immune response that results in damage and destruction of the muscle membrane

What is the result?

Both of these processes result in less ACh receptors on the muscle membrane. This makes it hard for enough ACh molecules to bind to enough ACh receptors on the muscle to trigger a muscle contraction. This causes the muscle weakness that affects those living with MG.1

MuSK and LRP4 proteins are involved in muscle contraction in more complicated ways. They help tell the body where to put ACh receptors on the muscle membrane. However, the immune system can also create antibodies against them.

When they are targeted by antibodies, the body does not properly organize ACh receptors on the muscle. Without the correct ACh receptor organization, the muscles will not properly respond to nerve ACh signals.2

Impact on treatment

Your doctor may prescribe different treatments according to which antibodies you have.

Pyridostigmine is a common MG drug that increases the amount of ACh in the neuromuscular junction. It works best in people with ACh receptor antibodies. It can also work in those who have MuSK antibodies. However, it is more likely to cause side effects in these people. They may need to be treated with other drugs.3

Doctors often also prescribe drugs that suppress your immune system. These include steroids, azathioprine, and mycophenolate mofetil. These drugs decrease the immune system’s attack of the neuromuscular junction triggered by the antibodies. These drugs often work well regardless of which MG antibodies you have.3

For those with a thymoma, doctors often recommend removing the thymus. This can cure or significantly decrease MG symptoms in some people. Doctors do not recommend removing your thymus if you do not have a thymoma.3

What is next?

Researchers continue to study MG and the antibodies related to MG. They hope to create treatments that are specific to each type of antibody. If you have more questions about your MG antibodies or your MG treatment, speak to your doctor.

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