Antibody Testing for Myasthenia Gravis Diagnosis
Order acetylcholine receptor (AChR) antibodies first, followed by muscle-specific kinase (MuSK) antibodies if AChR is negative, and include antistriated muscle antibodies in the initial workup. 1, 2, 3
Primary Antibody Panel (Order These First)
1. Anti-Acetylcholine Receptor (AChR) Antibodies
- This is your first-line test and confirms diagnosis in approximately 80% of patients with generalized myasthenia gravis 2, 3, 4
- Sensitivity drops to only 50% in purely ocular myasthenia gravis 3, 4
- Positive result definitively confirms the diagnosis 2, 4
2. Anti-Muscle-Specific Kinase (MuSK) Antibodies
- Order this when AChR antibodies are negative 1, 2, 3
- Approximately one-third of AChR-seronegative patients will be MuSK-positive 3, 4, 5
- MuSK-positive patients have distinctive clinical features including predominant bulbar weakness and may require different treatment approaches 6, 7
3. Antistriated Muscle Antibodies
- Include in the initial workup alongside AChR testing 1, 2
- These antibodies react with muscle proteins including titin, ryanodine receptor (RyR), and Kv1.4 8
- Presence indicates more severe disease and higher likelihood of thymoma (10-20% association) 3, 8
- Anti-Kv1.4 antibody specifically warns of potential lethal autoimmune myocarditis 8
Secondary Antibody Testing (If Above Are Negative)
4. Anti-Lipoprotein-Related Protein 4 (LRP4) Antibodies
- Consider when both AChR and MuSK antibodies are negative 1, 5
- Identifies a subset of previously "seronegative" patients 5
Critical Pitfall to Avoid
Do not stop testing after negative AChR antibodies. Up to 20% of myasthenia gravis patients are AChR-negative, and approximately 66% of these "seronegative" patients actually have low-affinity AChR antibodies detectable by specialized techniques or will be positive for MuSK or LRP4 antibodies 9, 5. The term "seronegative myasthenia gravis" is increasingly recognized as a misnomer, as most have detectable antibodies with appropriate testing 9.
Essential Concurrent Testing (Not Antibodies, But Order Simultaneously)
While not antibody tests, these are part of the comprehensive diagnostic workup recommended by guidelines:
- Electrodiagnostic studies: Single-fiber EMG (>90% sensitivity) or repetitive nerve stimulation 1, 2, 3, 4
- Pulmonary function tests: Negative inspiratory force and vital capacity to assess respiratory muscle involvement 1, 2, 3, 4
- CPK, aldolase, ESR, CRP: To evaluate for concurrent myositis 1, 2, 4
- Troponin and ECG: If respiratory insufficiency or elevated CPK present, to rule out myocarditis 1, 2, 4
- CT chest with contrast: After diagnosis confirmation to evaluate for thymoma 3, 4