Test Catalog

Test ID: MUSK    
Muscle-Specific Kinase (MuSK) Autoantibody, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosis of autoimmune muscle-specific kinase (MuSK) myasthenia gravis

 

Second-order test to aid in the diagnosis of autoimmune myasthenia gravis when first-line serologic tests are negative

 

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

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See Myasthenia Gravis Evaluation with MuSK Reflex Algorithm in Special Instructions.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Fatigable weakness due to impaired synaptic transmission at the neuromuscular junction is characteristic of myasthenia gravis (MG). The diagnosis is made by clinical and electromyographic criteria. Positive autoimmune serology must be interpreted in the clinical and electrophysiological context and response to anticholinesterase medication. Most cases are autoimmune and are caused by IgG autoantibodies binding to critical postsynaptic membrane molecules (nicotinic acetylcholine receptor or its interacting proteins).(1) Autoantibody detection frequency is lowest in patients with weakness confined to extraocular muscles (71% muscle acetylcholine receptor: AChR binding).(2) Mayo Clinic’s first-line serological evaluation detects muscle AChR antibody in 92% of nonimmunosuppressed patients with generalized weakness due to MG. Muscle-specific kinase (MuSK) antibody is detectable in more than one-third of those seronegative for muscle AChR antibody (less than 4% of all patients).(3) Physiologically, MuSK is involved in integrating and stabilizing AChR clusters in the motor endplate. MuSK is activated when the nerve-derived proteoglycan agrin binds to its receptor, lipoprotein-related protein 4 (LRP4). Antibodies to LRP4 itself have been described in rare patients.(1)

 

Six percent of nonimmunosuppressed patients with generalized MG lack demonstrable AChR or MuSK antibodies (double seronegative). Other rare autoantibodies no doubt remain to be discovered in such cases. However, as in autoimmune AChR MG and MuSK MG, testing for common organ-specific and nonorgan-specific autoantibodies is a valuable ancillary investigation in evaluating seronegative acquired generalized MG. General serological testing, coupled with family or personal history, will disclose autoimmune phenomena in 77% of those cases.(3) These disorders may include thyroid disease, type 1 diabetes, vitiligo, premature greying, rheumatoid arthritis, or lupus. Testing may also reveal antinuclear antibodies, glutamic acid decarboxylase (GAD65) antibodies, thyroperoxidase/thyroglobulin antibodies, or gastric parietal cell antibodies.(3) Objective improvement in strength following a therapeutic trial of plasmapheresis or intravenous immune globulin would justify consideration of long-term immunosuppression.

 

Females are generally affected by autoimmune MuSK MG more often than males. Onset can occur at any age (pediatric to elderly). Patients may derive limited benefit from anticholinesterase medication. The thymus is normal, and patients are generally not benefited by thymectomy. Antibody-lowering therapies are effective. Bulbar, facial, and respiratory weakness are prominent, and crises are common.(1,4)

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

Interpretation Provides information to assist in interpretation of the test results

A positive result, in the appropriate clinical context, confirms the diagnosis of autoimmune muscle-specific kinase myasthenia gravis.

 

Seropositivity justifies consideration of immunotherapy.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Immunosuppressant therapy is a common cause of false-seronegativity. It is, therefore, important to perform a comprehensive serological evaluation before initiating immunosuppressant therapy.

 

Interpretation of a patient’s serological and clinical status is further complicated when characteristic signs of myasthenia gravis are obscured by a superimposed steroid-induced myopathy.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Li Y, Arora Y, Levin K: Myasthenia gravis: Newer therapies offer sustained improvement. Cleve Clin J Med 2013 Nov;80(11):711-721

2. Lennon VA: Serological profile of myasthenia gravis and distinction from the Lambert-Eaton myasthenic syndrome. Neurology 1997;48 (Suppl 5):S23-S27

3. Chan KH, Lachance DH, Harper CM, Lennon VA: Frequency of seronegativity in adult-acquired generalized myasthenia gravis. Muscle Nerve 2007 Nov;36(5):651-658

4. Skjei KL, Lennon VA, Kuntz NL: Muscle specific kinase autoimmune myasthenia gravis in children: A case series. Neuromuscul Disord 2013 Nov;23(11):874-882

Special Instructions Library of PDFs including pertinent information and forms related to the test