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Myasthenia gravis (MG) is an acquired disorder of neuromuscular transmission caused by the binding of pathogenic autoantibodies to muscle's postsynaptic nicotinic acetylcholine receptor (AChR). In a small minority of patients the pathogenic antibody is directed at the muscle-specific receptor tyrosine kinase (MuSK) antigen. The ensuing weakness in both cases reflects a critical loss of the AChR channel protein, which is required to activate the muscle action potential.
MG affects children (see MGEP / Myasthenia Gravis [MG] Evaluation, Pediatric) as well as adults. In adults with MG there is at least a 20% occurrence of thymoma or other neoplasm. Neoplasms are an endogenous source of the antigens driving production of autoantibodies.
Autoimmune serology is indispensable for initial evaluation and monitoring of patients with acquired disorders of neuromuscular transmission. The neurological diagnosis depends on the clinical context and electromyographic findings, and is confirmed more readily by the individual patient’s serological profile than by any single test.
Not all of the antibodies detected in this profile impair neuromuscular transmission (eg, antibodies directed at cytoplasmic epitopes accessible on solubilized AChR, or sarcomeric proteins that constitute the striational antigens).
See Myasthenia Gravis: Adult Diagnostic Algorithm in Special Instructions.
Initial evaluation of patients aged 20 or older with symptoms and signs of acquired myasthenia gravis (MG)
Bone marrow transplant recipients with suspected graft-versus-host disease, particularly if weakness has appeared
Confirming that a recently acquired neurological disorder has an autoimmune basis (eg, MG)
Providing a quantitative baseline for future comparisons in monitoring a patient's clinical course and the response to immunomodulatory treatment
Raising likelihood of neoplasia
If muscle acetylcholine receptor (AChR) modulating antibody value is (or exceeds) 90% AChR loss and striational antibody is detected, thymoma is likely. Reflexive testing will include collapsin response-mediated protein-5-lgG Western blot, ganglionic AChR antibody, glutamic acid decarboxylase (GAD65) antibody, and voltage-gated potassium channel complex (VGKC) antibody (which are frequent with thymoma).
Note: Single antibody tests may be requested in follow-up of patients with positive results documented in this laboratory.
The patient's autoantibody profile is more informative than the result of any single test for supporting a diagnosis of myasthenia gravis (MG), and for predicting the likelihood of thymoma (see MGETH / Myasthenia Gravis [MG] Evaluation, Thymoma).
Muscle acetylcholine receptor (AChR) and striational autoantibodies are characteristic but not diagnostic of MG. One or both are found in 13% of patients with Lambert-Eaton Syndrome (LES), but P/Q-type calcium channel autoantibodies are very rare in MG.
Results are sometimes positive in patients with neoplasia without evidence of neurological impairment.
Titers are generally higher in patients with severe weakness, or with thymoma, but severity cannot be predicted by antibody titer.
Test results for muscle acetylcholine receptor and striational antibodies may be negative for 6 to 12 months after MG symptom onset. Only 8% of nonimmunosuppressed patients with generalized MG remain seronegative beyond 12 months for all autoantibodies in the adult MG evaluation. Of those patients 38% will have the alternative muscle-specific receptor tyrosine kinase (MuSK)-specific autoantibody.
MuSK antibody-positive patients lack thymoma, and have predominantly oculobulbar symptoms that respond to plasmapheresis and immunosuppressant therapy. They do not benefit from thymectomy.
A positive result is not per se diagnostic of myasthenia gravis (MG). Positive values for muscle antibodies (acetylcholine receptor: AChR or striational) occur in 13% of Lambert-Eaton syndrome (LES) patients, 40% of patients with autoimmune liver disorders, approximately 10% of patients with lung cancer, and in patients with graft-versus-host disease, and recipients of D-penicillamine.
In this laboratory, false-positive results for AChR binding antibodies are excluded by retesting positive sera with (125)I-alpha-bungarotoxin in the absence of muscle AChR. False-positive results occur most frequently in the bioassay for AChR modulating antibody; serum redraw will be requested when only this assay yields a positive result. Curare-like drugs used during general anesthesia can yield transient false-positive results for AChR modulating antibodies.
Seropositive rates differ in different laboratories.
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 specimen received in the laboratory will be held 1 week and assayed if sufficiently decayed, or canceled if radioactivity remains.
ACh RECEPTOR (MUSCLE) BINDING ANTIBODY
< or =0.02 nmol/L
ACh RECEPTOR (MUSCLE) MODULATING ANTIBODIES
0-20% (reported as __% loss of AChR)
STRIATIONAL (STRIATED MUSCLE) ANTIBODIES
1. Lennon VA: Serological profile of myasthenia gravis and distinction from the Lambert-Eaton myasthenic syndrome. Neurology 1997;48(Suppl 5):S23-S27
2. Harper CM, Lennon VA: Lambert-Eaton syndrome. In Current Clinical Neurology: Myasthenia Gravis and Related Disorders. Edited by HJ Kaminski. Totowa, NJ, Humana Press, 2002, pp 269-291
3. Hoch W, McConville J, Helms S, et al: Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 2001 Mar;7(3):365-368
4. Chan KH, Lachance DH, Harper CM, Lennon VA: Frequency of seronegativity in adult-acquired generalized myasthenia gravis. Muscle Nerve 2007;36:651-658
5. Skjei KL, Lennon VA, Kuntz NL: Muscle specific kinase antibody-associated myasthenia gravis in children; clinical, serologic, electrophysiologic and pathologic characteristics and response to treatment. Ann Neurol 62(S11):S145-S146