Blood Testing for Myasthenia Gravis
For suspected myasthenia gravis, order anti-acetylcholine receptor (AChR) antibodies first, followed by anti-MuSK antibodies if AChR is negative, and consider anti-LRP4 antibodies in double-seronegative cases. 1, 2
Initial Serological Testing Algorithm
Start with anti-AChR antibodies as the first-line blood test, as these are present in 80-85% of patients with generalized myasthenia gravis, though only 50% of purely ocular cases will be positive. 1, 3 The American Academy of Neurology specifically recommends this as the initial diagnostic step. 1
Sequential Testing Approach
If AChR antibodies are negative, proceed immediately to anti-muscle-specific kinase (MuSK) antibodies, as approximately one-third of seronegative patients will be MuSK-positive (5-8% of all MG patients). 1, 3
If both AChR and MuSK antibodies are negative, consider testing for anti-lipoprotein receptor-related protein 4 (LRP4) antibodies, though these are found in less than 1% of cases. 3, 4
Approximately 10% of patients remain seronegative for all known antibodies despite having clinical myasthenia gravis. 3
Assay Method Considerations
The radioimmunoprecipitation assay (RIPA) has been the historical standard with nearly 100% specificity for AChR antibodies, but sensitivity ranges only 50-92%. 5 Cell-based assays (both fixed and live) demonstrate higher sensitivity than RIPA and are increasingly recommended, particularly for detecting MuSK antibodies where RIPA has notably lower performance. 5
A complete reflex testing algorithm on the first pretreatment sample is now recommended, starting with binding and blocking assays for AChR antibodies, then reflexing to MuSK antibodies if negative, followed by clustered live cell-based assays if both are negative. 5
Additional Blood Tests for Differential Diagnosis
While not specific for myasthenia gravis, obtain anti-striational muscle antibodies when AChR antibodies are positive, as these help identify patients with thymoma—present in 10-20% of AChR-positive MG patients. 2, 6 Approximately 30-50% of patients with thymomas have myasthenia gravis, and in 20% of thymoma patients, mortality is related to MG complications. 2
Critical Timing Considerations
Do not delay treatment while waiting for antibody results. 1 The American Academy of Neurology emphasizes that clinical suspicion combined with bedside testing (ice pack test) and electrodiagnostic studies should guide immediate management decisions, with serological confirmation following. 1
Common Pitfalls to Avoid
Never rule out myasthenia gravis based on negative AChR antibodies alone, as 15-20% of generalized MG and 50% of ocular MG will be AChR-negative. 1, 3
Recognize that purely ocular myasthenia has significantly lower antibody positivity rates (40-77% for AChR) compared to generalized disease, making clinical and electrodiagnostic testing more critical in these cases. 2
Important clinical context: Patients with MuSK-positive MG often have distinct clinical features including prominent bulbar and facial weakness, may respond poorly to acetylcholinesterase inhibitors, and typically require different treatment approaches than AChR-positive patients. 3, 7, 4
Preoperative Testing Requirements
Any patient with suspected myasthenia gravis requiring surgery must have serum anti-AChR antibody levels measured preoperatively to avoid respiratory failure during anesthesia. 2 This is particularly critical given that respiratory compromise represents a life-threatening complication requiring immediate recognition. 1