Acetylcholine receptor antibody | Pathology Tests Explained

What is being tested?

Acetylcholine receptor (ACHR) antibodies are autoantibodies produced by the immune system that mistakenly target proteins called acetylcholine receptors that are located on skeletal muscle fibres. This test detects and measures ACHR antibodies in the blood.

Acetylcholine receptors function as "docking stations" for acetylcholine, a chemical substance (neurotransmitter) that transmits messages between nerve cells. Muscle movement starts when an impulse is sent down a nerve to the nerve ending, where it stimulates the release of acetylcholine. Acetylcholine travels across a microscopic gap between the nerve ending and a muscle fibre at the "neuromuscular junction." When it reaches the muscle fibre, it binds to one of many acetylcholine receptors and activates it, initiating muscle contraction.

ACHR antibodies impede communication between nerves and skeletal muscles, inhibit muscle contraction, and cause rapid muscle fatigue by preventing activation of the acetylcholine receptors. They do this in three major ways:

When they bind to the receptors, the antibodies may initiate an inflammatory reaction that destroys them.
The antibodies may sit on the receptors, preventing acetylcholine from binding.
The antibodies may cross-link the receptors, causing them to be taken up into the muscle cell and removed from the neuromuscular junction.

The end result of this interference is the development of myasthenia gravis (MG), a chronic autoimmune disorder associated with the presence of these antibodies and with their effects on muscle control.

ACHR antibodies may be detected in different ways to determine which mechanism may be the problem in a particular individual, and the antibodies may be referred to as "binding," "blocking," or "modulating." However, the technique that measures "binding" is the most commonly performed and, generally speaking, it is rare for the other two tests to be positive without the "binding" test being positive as well. These other approaches may be useful when the doctor strongly suspects myasthenia gravis and the "binding" test is negative. These are not available in routine laboratories in Australia.

How is it used?

An acetylcholine receptor (ACHR) antibody test is used to help diagnose myasthenia gravis (MG) and to distinguish it from other conditions that may cause similar symptoms, such as chronic muscle fatigue and weakness.

ACHR antibodies hinder the action of acetylcholine, a chemical (neurotransmitter) that transmits messages between nerve cells. The antibodies do this in three major ways:

"Binding" antibodies attach to the acetylcholine receptors on nerve cells and may initiate an inflammatory reaction that destroys them.
"Blocking" antibodies may sit on the receptors, preventing acetylcholine from binding.
"Modulating" antibodies may cross-link the receptors, causing them to be taken up into the muscle cell and removed from the neuromuscular junction.

Three different types of tests are available to determine which of these may be the problem in a particular individual. However, the test that measures "binding" antibodies is most commonly used because it is generally rare for the other two tests to be positive without the "binding" test being positive as well.

One or more of the ACHR antibody tests may be ordered as part of a panel of tests that may also include a striated muscle antibody test to help establish a diagnosis. Depending upon results, an anti-MuSK (muscle-specific kinase) antibody test may also be ordered.

The ACHR antibody test may be ordered initially as a baseline test and then as indicated to evaluate MG disease activity and/or response to therapy.

People with MG often have an enlarged thymus gland and may have thymomas (typically benign tumours of the thymus). Located under the breastbone, the thymus is an active part of the immune system during childhood but normally becomes less active after puberty. If a thymoma is detected, such as during a chest computed tomography (CT) scan done for a different reason, then an ACHR antibody test may sometimes be used to determine whether the person has developed these antibodies.

When is it requested?

The ACHR antibody test may be ordered when a person has symptoms that suggest MG, such as:

Drooping eyelid
Double vision
Decreased eye movement control
Difficulty swallowing, chewing, with choking, drooling and gagging
Slurred speech
Weak neck muscles
Trouble holding up head
Difficulty breathing
Difficulty walking and an altered gait
Specific muscle weakness but normal feelings/sensations
Muscle weakness that worsens with sustained effort and improves with rest
When a person has been diagnosed with MG, an ACHR antibody test may be ordered occasionally to evaluate MG disease activity and/or response to therapy.

An ACHR antibody test may sometimes be ordered when a thymoma is detected.

What does the result mean?

ACHR antibodies are not normally present in the blood. They are autoantibodies and their presence indicates an autoimmune response.

If a person has ACHR antibodies and symptoms of MG, then it is likely that the person has this condition.

ACHR antibodies may be seen with some thymomas, in people who are being treated with drugs such as penicillamine, with some small cell lung cancers, with autoimmune liver disease, and with Lambert-Eaton myasthenic syndrome (a condition associated with interference with the release of acetylcholine from the nerve ending).

A negative test result does not rule out MG. Up to 50% of those with ocular MG (affecting only eye-related muscles) and about 10-15% of those with generalized MG will be negative for ACHR antibodies.

In general, the greater the quantity of ACHR antibody, the more likely a person is to have significant symptoms, but the test results cannot be used to evaluate the severity of symptoms in a specific person.

Is there anything else I should know?

Use of drugs such as succinylcholine can increase ACHR antibodies.

People who have MG are more likely to also have other autoimmune disorders, such as rheumatoid arthritis or systemic lupus erythematosus.

Up to 70% of those suspected to have generalised MG but negative for ACHR antibodies will be positive for Anti-MuSK (muscle-specific kinase) antibodies.

Recent radioactive treatments can interfere with testing.

Common questions

Can myasthenia gravis (MG) be inherited?

As an autoimmune process, no. Some people may inherit a genetic defect that causes congenital myasthenic syndrome, a condition with similar symptoms.

Can MG be passed from one person to another?

MG is not contagious, but a pregnant woman with MG can pass some of her ACHR antibodies to her fetus. This can cause a newborn to have MG symptoms for several weeks after birth.

Can MG affect my heart?

No, the receptors for heart and smooth (digestive) muscles are different from skeletal muscles so they are not affected by the formation of ACHR binding antibodies.

Can this test be performed in my doctor's office?

No, it is specialised testing that is not offered by every laboratory. Your blood will likely need to be sent to a reference laboratory for testing.

How serious is MG?

Most people who have it can live a normal or near normal life with treatment and monitoring. One of the most serious complications is a respiratory myasthenic crisis that can occur when muscles that control breathing are weakened. This can be a medical emergency and often requires hospitalisation.