A 28-year-old woman with seronegative myasthenia gravis undergoes antibody testing. Which is the most common antibody found in seronegative myasthenia gravis patients?

Explanation

## Antibodies in Seronegative Myasthenia Gravis **Key Point:** Anti-MuSK (muscle-specific kinase) antibodies are found in 40–70% of seronegative MG patients, making them the most common antibody in this subgroup. ### Classification of MG by Serology | Antibody Type | Frequency in MG | Clinical Features | Pathophysiology | | --- | --- | --- | --- | | Anti-AChR | 80–85% of generalized MG | Generalized weakness, ocular signs | Complement-mediated destruction of AChR | | Anti-MuSK | 40–70% of seronegative MG | Bulbar/neck/respiratory weakness; less ocular | IgG4-mediated blockade of MuSK function | | Anti-LRP4 | <5% of seronegative MG | Rare; similar to anti-MuSK | Emerging; less well characterized | | Double seronegative | ~10% of MG | Variable; may have other antibodies | Unknown; possibly other NMJ proteins | ### Anti-MuSK Antibody Features **High-Yield:** MuSK is a receptor tyrosine kinase essential for neuromuscular junction development and maintenance. Anti-MuSK antibodies: - Are predominantly **IgG4** subclass (non-complement-fixing) - Cause functional blockade rather than destruction of the NMJ - Associated with **bulbar and neck weakness** as prominent features - Often show **less ocular involvement** compared to anti-AChR MG - May respond better to **immunosuppression** than anti-AChR MG - Have a **poorer response to anticholinesterase agents** ### Clinical Pearl **Clinical Pearl:** Seronegative MG with prominent bulbar weakness and poor response to anticholinesterase should raise suspicion for anti-MuSK antibodies. Testing for anti-MuSK is essential in all seronegative patients before labeling them as "double seronegative." ### Mnemonic **Mnemonic:** **MuSK = Muscle-Specific Kinase** — remember that anti-MuSK is the most common antibody in seronegative disease and is associated with **more bulbar/respiratory symptoms** and **less ocular** involvement. ### Anti-LRP4 and Double Seronegative **Warning:** Anti-LRP4 antibodies are rare (<5%) and not yet routinely tested. Many "seronegative" patients may actually have anti-MuSK or other unidentified antibodies. True double-seronegative MG exists but is uncommon.