Acetylcholine receptor (AChR) antibodies are autoantibodies produced by the immune system that mistakenly target proteins called acetylcholine receptors that are located on muscles that you can consciously or voluntarily control (known as skeletal muscle fibers). This test detects and measures AChR antibodies in the blood.
Muscle movement starts when an impulse is sent down a nerve to the nerve ending, where it stimulates the release of acetylcholine, a chemical substance (neurotransmitter) that transmits messages between specific types of cells. Acetylcholine travels across the very small gap between the nerve ending and a muscle fiber (this gap is called the "neuromuscular junction").
When acetylcholine reaches the muscle fiber, it binds to one of many acetylcholine receptors or "docking stations" 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:
- Binding antibodies attach to the receptors on nerve cells and may initiate an inflammatory reaction that destroys the receptors.
- 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.
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, 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 two tests may be useful when a healthcare practitioner strongly suspects myasthenia gravis and the "binding" test is negative.
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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. Repeat testing of AChR antibodies in those with initially negative results may be useful as the concentration of antibodies may increase as the disease progresses, resulting in a subsequent positive AChR antibody test result.
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AChR antibodies are not normally present in the blood. They are autoantibodies and their presence indicates an autoimmune response.
If you have AChR antibodies and symptoms of myasthenia gravis (MG), then it is likely that you have this condition. The extent to which AChR antibodies are elevated does not predict the severity of the disease at the time of diagnosis. However, changes in AChR antibody concentrations over time may help inform the effectiveness of treatment or predict the recurrence of disease. Therefore, repeat testing of AChR antibodies may be requested in some cases.
AChR antibodies may also be positive with some thymomas, in people who are being treated with drugs such as penicillamine, with some small cell lung cancers, with autoimmune liver disease, with Guillain-Barre syndrome, and with Lambert-Eaton myasthenic syndrome (a condition associated with interference with the release of acetylcholine from the nerve ending).
Results from other tests for autoantibodies, such as anti-MuSK (muscle-specific kinase) antibody test, anti-LRP4 (LDL-receptor-related protein 4) antibody test, and anti-striated muscle antibody test, may also aid in establishing a diagnosis.
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Potential symptoms of myasthenia gravis (MG) may include:
Muscle weakness caused by myasthenia gravis worsens as the affected muscle is used. Because symptoms usually improve with rest, muscle weakness can come and go. However, the symptoms tend to progress over time, usually reaching their worst within a few years after the onset of the disease.
Although myasthenia gravis can affect any of the muscles that you control voluntarily, certain muscle groups are more commonly affected than others.
Eye muscles:
In more than half of people who develop myasthenia gravis, their first signs and symptoms involve eye problems, such as:
- Drooping of one or both eyelids (ptosis)
- Double vision (diplopia), which may be horizontal or vertical, and improves or resolves when one eye is closed
Face and throat muscles:
In about 15% of people with myasthenia gravis, the first symptoms involve face and throat muscles, which can:
- Impair speaking. Your speech might sound soft or nasal, depending on which muscles have been affected.
- Cause difficulty swallowing. You might choke easily, making it difficult to eat, drink or take pills. In some cases, liquids you're trying to swallow come out your nose.
- Affect chewing. The muscles used for chewing might wear out halfway through a meal, particularly if you've been eating something hard to chew, such as steak.
- Change facial expressions. For example, your smile might look like a snarl.
Neck and limb muscles:
Myasthenia gravis can also cause weakness in your neck, arms and legs. Weakness in your legs can affect how you walk. Weak neck muscles make it hard to hold up your head.
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