Disease Severity in MuSK Myasthenia Gravis Could Correlate to Antibody Levels

A new study published in the Journal of Neuroimmunology¹ indicates that disease severity of muscle-specific kinase (MuSK) myasthenia gravis (MG) could be linked to MuSK antibody levels. The researchers also found that immunoglobulin G levels were not helpful in determining disease severity.

MG, an autoimmune disorder, is primarily categorized by muscle weakness that mainly affects the face and neck muscles as well as overall fatigue. About 3% of those with MG in Japan have autoantibodies against MuSK.² MuSK antibodies do not usually activate the complement but are mediated by pathogenic autoantibodies like immunoglobulin G4 (IgG4). The use of MuSK antibodies to measure disease severity has been less popular due to conflicting findings. MuSK antibody measurements have been used in Japan in the past, which led to the researchers investigating the relationship by retrospectively evaluating a cohort of Japanese patients to assess the relationship between MuSK antibody levels and clinical symptoms.

Data from January 1, 2013, to December 31, 2024, were analyzed for this study, with all patients having MuSK-MG and being immunotherapy naive. Patients included in this study had all available data from the MG Activities of Daily Living (MG-ADL) scores, and MuSK antibody levels were measured and reported. Generalized linear mixed-effects models were used to assess the relationship, and a separate generalized linear mixed-effects model analysis was used to assess the specificity in correlation.

There were 6 patients included in the study who had been diagnosed with MuSK-MG and followed longitudinally starting at their immunotherapy-naive state. The patients contributed 103 data points for the primary analysis and 81 data points for the secondary analysis. For the primary analysis, there was a significant positive intrapatient correlation between MG-ADL scores (F ratio = 17.48), with this finding supported by a scatter plot evaluating each individual patient.

A secondary analysis was done to assess whether the correlation with MuSK antibodies was just a reflection of general immune status. The analysis included both MuSK antibody levels and total IgG level as fixed effects. This secondary analysis found that MuSK antibody level was positively, significantly, and specifically correlated with MG-ADL score (F ratio = 10.97), whereas total IgG level had no independent correlation (F ratio = 0.27).

There were some limitations to this study. The sample size of the study was small and requires further studies to confirm the findings with larger populations. All patients came from a single center, potentially limiting generalizability. The study design was retrospective, which could introduce selection bias. Patients with a larger number of data points could have influenced the results of the study. Interpatient correlation could not be determined due to the small sample size of the study.

The researchers concluded that “MuSK antibody levels serve a specific clinical role in correlating with intrapatient disease activity.” The finding, they wrote, shows the utility of MuSK antibody levels as a means of monitoring therapeutic response, as it is indicative of a specific pathogenic process. Future studies will need to confirm the finding in larger cohorts of patients diagnosed with MuSK-MG.

References

1. Yasuda M, Uzawa A, Ogaya E, et al. Longitudinal MuSK antibody levels may correlate with disease severity in MuSK myasthenia gravis. J Neuroimmunol. 2026;414:578876. doi:10.1016/j.jneuroim.2026.578876
2. Suzuki S, Masuda M, Uzawa A, et al. Japan MG registry: chronological surveys over 10 years. Clin Exp Neuroimmunol. 2022;14(1):5-12. doi:10.1111/cen3.12731