Antibody Positivity Rates in Myasthenia Gravis
In patients suspected of having myasthenia gravis, approximately 80% with generalized disease test positive for acetylcholine receptor (AChR) antibodies, while only 50% with purely ocular disease are AChR-positive; among those who are AChR-negative, approximately one-third (33%) will be positive for muscle-specific kinase (MuSK) antibodies. 1
AChR Antibody Positivity
- AChR antibodies are present in approximately 80% of patients with generalized myasthenia gravis, making this the most common antibody detected 1, 2
- In purely ocular myasthenia gravis, AChR antibody sensitivity drops significantly to only 50% 1, 2
- A recent 2025 meta-analysis of 44 studies (n=4,937 patients with ocular MG) confirmed 59% pooled positivity for anti-AChR antibodies (95% CI: 52%-66%) 3
- AChR antibody positivity carries important prognostic implications: patients with positive AChR antibodies have 1.82 times greater risk of progressing from ocular to generalized myasthenia gravis (95% CI: 1.15-2.88) 3
- Thymoma prevalence is 35% (95% CI: 3%-90%) in AChR-positive ocular myasthenia patients, underscoring the critical importance of detecting these antibodies 3
MuSK Antibody Positivity
- Among AChR-negative patients, approximately one-third (33%) will test positive for anti-MuSK antibodies 1, 2
- In the general myasthenia gravis population, MuSK antibodies are detected in approximately 6% of all patients 4
- In purely ocular myasthenia gravis, MuSK antibody positivity is only 5% (95% CI: 2%-9%) based on pooled analysis of 34 studies (n=3,380 patients) 3
- A landmark 2001 study demonstrated that 70% of AChR-antibody-seronegative MG patients have MuSK antibodies 5
Other Antibodies and Seronegative Disease
- Approximately 10% of myasthenia gravis patients remain seronegative by conventional AChR and MuSK testing 4
- Using more sensitive detection methods in previously seronegative patients reveals: 25% have AChR antibodies, 4% have MuSK antibodies, 7% have LRP4 antibodies, and 6% have titin antibodies when tested with highly sensitive assays 6
- In total, 37% of conventionally seronegative MG patients test positive for at least one antibody when comprehensive testing with sensitive methods is performed 6
- LRP4 (low-density lipoprotein receptor-related protein 4) antibodies represent a third autoantigen in myasthenia gravis, though less commonly detected 4
Double-Positive Antibodies
- Double seropositivity for both AChR and MuSK antibodies is extremely rare, occurring in only 0.1% of patients (4 out of 5,180 patients across 62 studies) 3
- Patients with coexistence of multiple antibodies tend to have more severe disease compared to single-antibody or seronegative patients 6
Clinical Testing Algorithm
- Always test AChR antibodies first as the initial diagnostic test, given the 80% positivity rate in generalized disease 1, 2
- Test MuSK antibodies only when AChR antibodies return negative, as this sequential approach is more cost-effective given MuSK's lower prevalence and higher testing cost 1, 2, 3
- Consider anti-striated muscle antibodies in the initial workup, particularly given the association with thymoma 1
- In patients remaining seronegative after conventional testing, consider referral for highly sensitive radioimmunoassays or cell-based assays that can detect antibodies missed by routine methods 6