ACETYLCHOLINE RECEPTOR BLOCKING AB
- ACETYLCHOLINE RECEPTOR BLOCKING AB
- Start Date
- Expiration Date
- AChR Blocking Ab; Myasthenia Gravis Ab
- CPT Codes
- Reference Test
- Transport Info
Centrifuge and immediately transfer serum to separate plastic tube
- Fasting Required?
- Patient Instructions
- Reference Range
Negative: 0-15% blocking
Indeterminate: 16-24% blocking
Positive: Equal to or greater than 25%
Semi-Quantitative Radioreceptor Assay
Approximately 90% of patients with myasthenia gravis MG) express antibodies to the acetylcholine receptor (aChR), which can be divided into binding, blocking, and modulating antibody. Binding antibody can activate complement and lead to loss of aChR. Blocking antibody may impair aChR binding 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. Approximately 10% of individuals with confirmed myasthenia gravis have no measurable binding, blocking, or modulating antibody.
Myasthenia gravis (MG) is an autoimmune disease in which an acetylcholine receptor (AChR) is the antibody target. The AChR in the motor end-plate of skeletal muscle is an integral membrane protein consisting of five subunits (a pentamer). The alpha chain carries both the binding site for cholinergic ligands (binding site for acetylcholine and bungarotoxin) and the main immunogenic region, a region against which a majority of the antibodies of MG patients are directed. In MG, acetylcholine-dependent neuromuscular transmission is impaired by a loss of signal transduction. The final result is that threshold potential in the cell is never reached and the muscle cannot contract. The patient experiences voluntary muscle weakness and fatigue characteristic of the disease, as well as difficulty in swallowing, diplopia, ptosis (in ocular MG), and, in severe cases, death. Individuals who manifest AChR antibodies generally do not express a single, monoclonal antibody population. The antibody population is divided into three classes: • Binding • Blocking • Modulating Binding antibodies are those that are epitopically directed toward the large hydrophilic domain of the receptor. This class of antibodies can activate the complement cascade, resulting in tissue damage and receptor loss. The AChR binding antibody radioimmunoassay detects a wide population of autoantibodies. The use of soluble receptor measures not only antibody directed against the extracellular region of the receptor, presumably the portion involved in the pathophysiology of the disease, but intracellular determinants of the receptor not normally exposed to immunoglobulins. The assay is incapable of differentiating general binding antibodies from the more specific modulating population. Moreover, the binding assay does not easily measure a blocking population. Blocking autoantibodies prevent the binding of acetylcholine to the receptor. They may act by direct steric interference or by an allosteric mechanism. The pathology associated with this type of antibody will result in the most rapid loss of receptor function. Modulating antibodies as a class accelerate endocytosis, resulting in loss of receptors. It is largely this class of antibodies to which clinical severity has been most closely associated. In fifty-three percent of samples with any measurable autoantibody, all three antibody populations were present. Addition of blocking and modulating antibody assays to the binding assay increased the number of samples that tested positive by approximately 10 percent. Studies show that the presence of modulating antibody generally compares more closely to disease severity than either binding or blocking classes. Drachman et al showed that the blocking population has a disease severity correlation nearly as high as that of modulating antibodies (88% vs. 91%). Approximately 90 percent of patients with myasthenia gravis (MG) express antibodies to the acetylcholine receptor (AChR), which can be divided into binding, blocking, and modulating antibody. Binding antibody can activate complement and lead to loss of AChR. Blocking antibody may impair AChR binding 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. Approximately 10 percent of individuals with confirmed myasthenia gravis have no measurable binding, blocking, or modulating antibody.