Acetylcholine Receptor Antibody
Myasthenia gravis is an acquired autoimmune disease characterized by muscle weakness and progressive fatigability. The fundamental defect is failure of neuromuscular transmission due to formation of specific autoantibodies directed against the acetylcholine receptor (AChR) in the postsynaptic membrane of skeletal muscle. Binding of these autoantibodies prevents acetylcholine binding to the receptor, damages the postsynaptic membrane, and accelerates receptor degradation. Synaptic transmission fails when the autoantibodies cause a critical loss of the cation channel protein, which is required to activate the muscle action potential.
Acetylcholine receptor (AChR) binding antibody is positive in approximately 90% of nonimmunosuppressed patients with generalized MG. AChR autoantibodies can be divided into binding, blocking and modulating antibodies. Binding antibody can activate complement and lead to loss of AChR. Blocking antibody may impair binding of acetylcholine to the receptor, leading to poor muscle contraction. Modulating antibody causes receptor endocytosis resulting in loss of AChR expression, which correlates most closely with clinical severity of disease.
Detection of AChR binding antibodies supports a diagnosis of acquired myasthenia gravis in patients with supportive clinical and electrophysiological findings. Antibody levels are usually high in generalized myasthenia gravis and in myasthenia gravis associated with thymoma. Results may be negative during the first 12 months after symptom onset or during immunosuppressant therapy. The frequency of AChR binding antibody detection is lower (70%) in MG patients with weakness clinically restricted to ocular muscles. Positive AChR results may also be found in patients with Lambert Eaton Syndrome and autoimmune liver disease. Generally, there is not a good correlation between antibody titer and the severity of weakness.
AChR binding antibody is recommended as the initial case finding test because it is faster and more economical to perform. AChR modulating antibodies are indicated when AChR binding antibody is negative and when myasthenia gravis is mild, ocular restricted, or of less than one-year duration.
Autoantibodies directed against the contractile proteins of striated muscle are present in approximately 35 percent of patients with myasthenia, but in 80 percent of those with thymoma. These antibodies may be a useful serological marker for the diagnosis of thymoma in those patients with early onset myasthenia gravis occurring between 20 and 50 years of age. In this cohort, thymoma can be found in 60 percent of patients with anti-striated muscle antibodies, but in less than 10 percent of those without these antibodies. The false-positive rate (striational antibodies present without thymoma) is under 10 percent, but it rises to 50 percent in those 40 to 50 years of age or older. This test is most predictive of thymoma when accompanied by positive CRMP-5 IgG and acetylcholine receptor modulating autoantibodies.
These antibodies may also be detected in patients with: Lambert-Eaton myasthenic syndrome, small-cell lung carcinoma, breast carcinoma, patients with rheumatoid arthritis treated with D-penicillamine, bone marrow transplant recipients having graft-versus-host disease, and autoimmune liver disorders.
Reference ranges are:
AchR binding antibody – 0 to 0.4 nmol/L
AchR blocking antibody – 0 to 26 percent blocking
AchR modulating antibody – 0 to 20% loss of AchR
Specimen requirement is a red top of tube of blood.
