What is the recommended blood test for diagnosing Myasthenia Gravis (MG)?

Recommended Blood Tests for Diagnosing Myasthenia Gravis

Anti-acetylcholine receptor (anti-AChR) antibody testing should be the initial blood test for diagnosing myasthenia gravis, followed by anti-muscle-specific kinase (anti-MuSK) antibody testing if AChR antibodies are negative. 1

Primary Antibody Testing

First-Line Testing

• Anti-AChR antibody testing:
  • Detects antibodies in approximately 80-85% of patients with generalized MG
  • Detects antibodies in approximately 50% of patients with ocular MG
  • Should be performed using radioimmunoprecipitation assay (RIPA) which has nearly 100% specificity but sensitivity between 50-92% 2

Second-Line Testing (if AChR antibody negative)

• Anti-MuSK antibody testing:
  • Present in 6-10% of MG patients
  • Particularly important in AChR-negative generalized MG
  • Associated with distinct clinical features including prominent neck, bulbar, and respiratory muscle involvement 1, 3

Third-Line Testing (if both AChR and MuSK antibody negative)

• Anti-LRP4 (lipoprotein receptor-related protein 4) antibody testing:
  • Present in 2-50% of previously seronegative MG cases 2
  • Emerging as an important diagnostic marker

Advanced Testing for Seronegative Cases

For patients who test negative with conventional assays but have strong clinical suspicion of MG:

• Cell-based assays (CBAs) for AChR and MuSK antibodies:

  • Higher sensitivity than traditional RIPA methods 2
  • Available as fixed cell-based assays (f-CBA) or live cell-based assays (L-CBA)

• Clustered AChR cell-based assay:

  • Can detect low-affinity AChR antibodies missed by standard tests
  • May identify antibodies in up to 66% of previously seronegative patients 4
  • Uses AChR clustered with rapsyn protein to better mimic neuromuscular junction conditions

Additional Antibody Testing (Based on Clinical Context)

• Anti-striated muscle antibodies (anti-titin, anti-ryanodine receptor):

  • Particularly useful when thymoma is suspected
  • Often present alongside AChR antibodies 1

• Other antibodies that may be considered in specific cases:

  • Anti-agrin antibodies
  • Anti-KV1.4 antibodies
  • Anti-cortactin antibodies 5

Recommended Testing Algorithm

1. Start with AChR binding and blocking antibody assays using RIPA and/or f-CBA
2. If AChR antibody negative, proceed to MuSK antibody testing using RIPA and/or CBA
3. If both AChR and MuSK antibodies are negative, consider clustered live cell-based assay (L-CBA) 2
4. Consider additional antibody testing based on clinical presentation

Important Considerations

• Antibody status helps determine prognosis and treatment selection
• AChR-positive MG generally has better prognosis than MuSK-positive MG 1
• Seronegative status does not rule out MG - clinical features and electrodiagnostic studies remain important
• Collect blood samples before immunomodulatory treatment when possible, as treatment may affect antibody levels
• A negative antibody test does not exclude the diagnosis of MG if clinical suspicion is high

Complementary Diagnostic Testing

While not blood tests, these are important complementary diagnostic approaches:

• Electrodiagnostic studies (repetitive nerve stimulation and single-fiber EMG)
• Edrophonium (Tensilon) test
• Ice pack test
• Pulmonary function assessment 1

Remember that antibody testing should be interpreted in the context of clinical presentation and other diagnostic tests, as no single test has 100% sensitivity for diagnosing MG.