Acetylcholine Receptor (Muscle AChR) Binding Antibody, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Myasthenia gravis (MG) is characterized by weakness and easy fatigability that are relieved by rest and anticholinesterase drugs. The weakness in most cases results from an autoantibody-mediated loss of functional acetylcholine receptors (AChR) in the postsynaptic membrane of skeletal muscle.
Demonstration of muscle AChR autoantibodies in a patient's serum supports the diagnosis of acquired (autoimmune) MG, and quantitation provides a baseline for future comparisons.
Muscle AChR antibodies are not found in congenital forms of MG and are uncommon in neurologic conditions other than acquired MG, with the exception of patients with paraneoplastic autoimmune neurological disorders, and Lambert-Eaton myasthenic syndrome (LES) with or without cancer (13% of LES patients have positive results for muscle AChR binding or striational antibodies). Patients with autoimmune liver disease are also frequently seropositive.
The assay for muscle AChR binding antibodies is considered a first-order test for the laboratory diagnosis of MG, and for detecting "subclinical MG" in recipients of D-penicillamine, in patients with thymoma without clinical evidence of MG, and in patients with graft-versus-host disease.
Confirming the diagnosis of myasthenia gravis (MG)
Distinguishing acquired disease (90% positive) from congenital disease (negative)
Detecting subclinical MG in patients with thymoma or graft-versus-host disease
Monitoring disease progression in MG or response to immunotherapy
An adjunct to the test for P/Q-type calcium channel binding antibodies as a diagnostic aid for Lambert-Eaton myasthenic syndrome (LES) or primary lung carcinoma
Values >0.02 nmol/L are consistent with a diagnosis of acquired myasthenia gravis (MG), provided that clinical/electrophysiological criteria support that diagnosis.
The assay for muscle acetylcholine receptor (AChR) binding antibodies is positive in approximately 90% of nonimmunosuppressed patients with generalized MG.
The frequency of antibody detection is lower in MG patients with weakness clinically restricted to ocular muscles (71%), and antibody titers are generally low in ocular MG (eg, 0.03-1.0 nmol/L).
Results may be negative in the first 12 months after symptoms of MG appear or during immunosuppressant therapy.
Note: In follow up of seronegative patients with adult-aquired generalized MG, 17.4% seroconvert to positive at 12 months (ie, seronegativity rate at 12 months is 8.4%). Thirty eight percent of persistently seronegative patients have muscle-specific kinase (MuSK) antibody.
Sera of nonmyasthenic subjects bind per liter 0.02 nmol or less of muscle AChR complexed with (125)I-labeled-alpha-bungarotoxin.
In general, there is not a close correlation between antibody titer and severity of weakness, but in individual patients, clinical improvement is usually accompanied by a decrease in titer.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Positive results for muscle acetylcholine receptor (AChR) binding or striational antibodies are found in 13% of patients with Lambert-Eaton myasthenic syndrome (LES). This does not mean that myasthenia gravis (MG) and LES co-exist. Antibodies to P/Q type calcium channels are found in 95% of LES patients, but not in MG, except in very rare paraneoplastic cases related to small-cell lung carcinoma.
Positive results are frequently found with autoimmune liver disease.
Magnitude of the result is not useful for predicting severity of MG.
This test should not be requested in patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. The specific waiting period before specimen collection will depend on the isotope administered, the dose given and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held 1 week and assayed if sufficiently decayed, or canceled if radioactivity remains.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
< or =0.02 nmol/L
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Lennon VA: Serological diagnosis of myasthenia gravis and distinction from the Lambert-Eaton myasthenic syndrome. Neurology 1997;48(Suppl 5):S23-S27
2. Lachance DH, Lennon VA: Chapter 19, Paraneoplastic neurological autoimmunity. In Neuroimmunology in Clinical Practice. Edited by B Kalman, T Brannagan III. Blackwell Publishing Ltd, 2008, pp 210-217