26306 Myasthenia Gravis Evaluation with Muscle-Specific Kinase (MuSK) Reflex, Serum (MGMR)

​​​​Acetylcholine Receptor (Muscle AChR) Antibodies, Ach Receptor Ab, AChR (Acetylcholine Receptor), AChR Receptor Blocking Ab, Anti-Skeletal Muscle Antibodies, Binding, Blocking, and Modulating Abs, Blocking Ab, Muscle End-Plate Antibodies, MUSK, MuSK myasthenia, Myasthenia Gravis Antibodies, Myasthenia Gravis, Myoid Antibody, Thymoma

​ACh Receptor (Muscle) Binding Ab

MuSK Autoantibody

​Diagnosing autoimmune myasthenia gravis (MG) in adults and children

Distinguishing autoimmune from congenital MG in adults and children or other acquired forms of neuromuscular junction transmission disorders

Establishing a quantitative baseline value that allows comparison with future levels if weakness is worsening

​Patient Preparation:

1. For optimal antibody detection, specimen collection is recommended prior to initiation of immunosuppressant medication or intravenous immunoglobulin treatment.​

2. 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.

Centrifuge and aliquot serum into a plastic vial. 

​These results should only be interpreted in the appropriate clinical and electrophysiological context and are not diagnostic in isolation.

Specimens should be collected prior to administration of immunosuppressant therapy as this may reduce the diagnostic sensitivity of the assay; the neurological diagnosis is further confounded if steroid myopathy develops.

Positive muscle acetylcholine receptor (AChR) may occur in autoimmune liver disorders and in patients with graft-versus-host disease and recipients of D-penicillamine.

Weakly positive results may occur with hypergammaglobulinemia and should be interpreted with caution in the appropriate clinical context.

AChR modulating antibodies will only be performed if AChR binding antibodies are present or if there is an interfering substance present which precludes testing for AChR binding antibodies.

Seropositive rates and quantitative results differ across laboratories and patient results tested at different laboratories should not be treated equivalently.

The presence of alpha-bungarotoxin antibodies may interfere with the AChR muscle binding antibody assay and therefore if detected, AChR binding results will not be reported. 

​Fatigable weakness due to impaired postsynaptic transmission at the neuromuscular junction is characteristic of myasthenia gravis (MG). A clinical diagnosis should be supported by electrodiagnostic testing, ie, clinical-electrodiagnosis (EDX). Positive autoimmune serology increases certainty of MG diagnosis but needs to be interpreted in the proper clinical-EDX context with response to anticholinesterase medications supporting the diagnosis. Most cases are autoimmune and are caused by IgG autoantibodies binding to critical postsynaptic membrane molecules (nicotinic muscle acetylcholine receptor [AChR] or its interacting proteins, such as muscle-specific kinase [MuSK]). Serologically, the detection of AChR binding antibody provides the best diagnostic sensitivity. However, the presence of both AChR binding and modulating activity improves diagnostic accuracy. Autoantibody detection frequency is lowest in patients with weakness confined to extraocular muscles (72% are positive for AChR binding antibodies) and highest in patients with generalized weakness due to MG (92% are positive for AChR binding antibodies). In adults with MG and AChR antibodies, approximately 20% will have thymoma and, very rarely (<1%), extrathymic cancers. Computerized tomography (CT) imaging of the chest is considered the standard of care to evaluate for thymoma.

MuSK antibody is detectable in more than one-third of patients with MG and are seronegative for muscle AChR antibodies. MuSK is involved in integrating and stabilizing AChR clusters at the motor endplate. MuSK is activated when the nerve-derived proteoglycan agrin binds to its receptor, lipoprotein-related protein 4 (LRP4). Patients with MuSK MG are more commonly female. Onset can occur at any age (pediatric to older adult). Patients derive less benefit from anticholinesterase medications and no neoplasm has associated with MuSK MG. Although beneficial, thymectomy has not been demonstrated to be helpful in MuSK MG. Patients with both AChR and MuSK autoantibodies benefit from immunotherapy, however, patients with MuSK autoantibodies tend to have more steroid dependence.

In patients with seronegative MG, reconsideration of the diagnosis is important. If clinical-EDX criteria are still met, repeating serological testing within one year can increase serological positivity for AChR antibodies by 15%. The diagnostic sensitivity of these tests depends on the disease severity and duration of symptoms. AChR binding antibodies may be undetectable for 6 to 12 months after MG symptom onset. Only about 5% of adult patients with generalized MG who at not immunosuppressed remain seronegative for muscle AChR beyond 12 months. Objective improvement by electrodiagnostic and strength testing following a therapeutic trial of plasmapheresis or intravenous immune globulin can justify consideration of long-term immunosuppression in patients who are seronegative meeting clinical-EDX criteria.

Note: Single antibody tests may be requested in the follow-up of patients with positive results previously documented in this laboratory.

Testing Algorithm:

If acetylcholine receptor (AChR)-binding antibodies are greater than 0.02 nmol/L, then AChR muscle modulating antibody will be performed at an additional charge.

If AChR-binding antibodies are 0.02 nmol/L or less, then muscle-specific kinase (MuSK) autoantibody will be performed at an additional charge.

If unable to report AChR binding antibody due to interfering substances, then AChR muscle modulating antibody will be performed at an additional charge.

If unable to report AChR binding antibody due to interfering substances and AChR muscle modulating antibody is negative, then MuSK autoantibody will be performed at an additional charge.

​Positive results in this antibody evaluation are indicative of autoimmune myasthenia gravis (MG). These results should be interpreted in the appropriate clinical and electrophysiological context.

In the presence of either acetylcholine receptor (AChR) antibodies a paraneoplastic basis should be considered with thymoma being the most commonly associated tumor with myasthenia gravis. Currently, muscle-specific kinase antibody positive MG is not associated with a paraneoplastic etiology.

Negative results do not exclude the diagnosis of an autoimmune neuromuscular junction disorder. If clinical suspicion remains and symptoms persistent or worsen consider re-testing.