Blood Tests for Diagnosing and Managing Myasthenia Gravis
The primary blood tests for diagnosing myasthenia gravis include anti-acetylcholine receptor (AChR) antibodies, anti-muscle-specific kinase (MuSK) antibodies, and anti-lipoprotein-related protein 4 (LRP4) antibodies, with additional testing for concurrent conditions and monitoring of treatment effects.
Primary Diagnostic Antibody Tests
Anti-Acetylcholine Receptor (AChR) Antibodies
- First-line serological test for suspected myasthenia gravis
- Positive in approximately 80-85% of patients with generalized myasthenia gravis 1
- Only positive in about 50% of patients with ocular myasthenia gravis 2
- Three types can be measured:
- Binding antibodies (most commonly tested)
- Blocking antibodies
- Modulating antibodies
Anti-Muscle-Specific Kinase (MuSK) Antibodies
- Should be tested when AChR antibodies are negative 2
- Positive in approximately one-third of AChR-negative patients 2
- Critical for diagnosis of MuSK-positive MG, which may respond differently to treatment 3
Anti-Lipoprotein-Related Protein 4 (LRP4) Antibodies
- Third well-established pathogenic antibody in MG 4
- Should be tested in patients negative for both AChR and MuSK antibodies 2
- Associated with both generalized and ocular myasthenia gravis 2
Additional Antibody Tests
Anti-Striated Muscle Antibodies
- Important to test alongside AChR antibodies 2
- Particularly useful for detecting thymoma association
- Positive in many patients with thymoma-associated MG 2
Other Antibodies (for specific clinical scenarios)
- Anti-titin antibodies
- Anti-ryanodine receptor (RyR) antibodies
- Anti-agrin antibodies
- Anti-Kv1.4 potassium channel antibodies
- Anti-cortactin antibodies 1, 4
Tests for Concurrent Conditions and Complications
Thymus Evaluation
- Chest imaging (CT/MRI) to evaluate for thymoma, especially in AChR-positive patients 2
- Thymoma is present in approximately 10-15% of MG patients
Tests for Concurrent Myositis
- Creatine phosphokinase (CPK)
- Aldolase
- Erythrocyte sedimentation rate (ESR)
- C-reactive protein (CRP) 2
Cardiac Evaluation (if respiratory symptoms or elevated CPK)
- Troponin T
- Electrocardiogram (ECG)
- Transthoracic echocardiogram (TTE) 2
Monitoring Tests During Treatment
Pulmonary Function Tests
- Negative inspiratory force (NIF)
- Vital capacity (VC)
- Critical for monitoring respiratory function, especially during crisis 2
Complete Blood Count and Metabolic Panel
- Monitor for side effects of immunosuppressive therapy
- Check creatinine weekly if on certain medications 2
Diagnostic Algorithm
Initial presentation with suspected MG symptoms (ptosis, diplopia, muscle weakness):
- Order AChR antibodies (binding, blocking, modulating) and anti-striated muscle antibodies
If AChR antibodies negative:
- Order anti-MuSK antibodies
- If still negative, order anti-LRP4 antibodies
If all antibody tests negative (seronegative MG):
For all confirmed MG patients:
- Check for concurrent conditions (myositis, cardiac involvement)
- Evaluate thymus with imaging
- Monitor pulmonary function if generalized symptoms present
Important Considerations
- Single-fiber electromyography is considered the gold standard for diagnosis with positivity in over 90% of patients with ocular myasthenia 2
- Cell-based assays have improved sensitivity for detecting antibodies in previously seronegative patients 5
- Antibody profile helps determine prognosis and treatment response 1
- Avoid medications that can worsen myasthenia gravis during treatment (β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, macrolides) 2, 6
Pitfalls to Avoid
- Not testing for MuSK and LRP4 antibodies when AChR antibodies are negative
- Missing concurrent conditions like myositis or cardiac involvement
- Failing to recognize that ocular myasthenia has lower antibody positivity rates than generalized MG
- Not considering cell-based assays for seronegative patients with strong clinical suspicion of MG
- Overlooking the need for pulmonary function testing in patients with generalized symptoms