Received Nov 10; Accepted Jul 4.
Background Anti-acetylcholine receptor antibodies are heterogeneous antibodies that cause loss of muscle function by several mechanisms. Existence of end plate protein was first suggested by Simpson inas he found globulins that could block binding of alpha bungaratoxin a polypeptide from venom of Bungarus multicinctus to acetylcholine receptor in rats.
The first detailed study was done by Lindstorm et al. It showed no correlation between acetylcholine receptor antibodies and various determinants like age, sex, duration of disease, or ethnicity.
The titers were much lower than those in patients with generalized MG in clinical remission. Other sites of production exist as antibodies remain positive in patients in clinical remission after thymectomy. Some authors believe that these antibodies may block the binding of acetylcholine to receptor by occupying their space, a theory based on the minimal decrease in the receptor density on end plates of muscle fibers.
Other researchers believe that difference in expression is due to variability in binding capacity of antibodies to the receptor, which determines further activation of the destruction process.
Other diseases with positive anti-acetylcholine receptor antibodies are lupus, rheumatoid arthritis, liver disease, autoimmune hepatitis, Lambert-Eaton syndrome, small cell lung cancer, and Graves disease. Positive anti-acetylcholine receptor antibodies are also seen in patients on immunosuppressive therapy.
Antibody levels are independent of variables like age, sex, ethnicity, and duration of disease. The only exception to this is in patients with paraneoplastic syndrome in small cell lung cancer. An inverse relation is described between antibody levels and B cell numbers as they increase the antibody clearance from the serum of the patient.
Anti-acetylcholine receptor antibody is helpful in diagnosing MG and is used as the first test in patients with clinical indicators of the disease. Its high sensitivity and specificity of Levels are also used to differentiate the congenital form of MG from the acquired form as antibody is negative in former.
Antibody positivity also helps in deciding the type of treatment in patients without thymoma. Researchers have seen beneficial outcomes of thymectomy in antibody-positive patients without thymoma and borderline or no improvement in patients with low antibody titers and no thymoma seronegative MG.
These tests are part of the reflex panel for diagnosing MG. Negative antibody levels do not rule out MGand other tests, like single fiber electromyography or repetitive muscle stimulation, can be performed to confirm the diagnosis of MG.
Other conditions, like thyoma without MG, can also be associated with high titers of antibody, and antibody can be detected in patients with recent radiation exposure or patients receiving immunosuppressive treatment especially those receiving D-pencillamine therapy.
Seronegative MG patients are those who have the typical symptoms of MG but do not carry detectable levels of anti-AChR antibodies in their serum. These patients are often found to have anti-MuSk antibody and anti-striated muscle antibody in their serum.
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Media Gallery Acetylcholine receptor. Note 5 subunits, each with 4 membrane-spanning domains forming a rosette with a central opening.
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