To validate a quantitative assay to measure antibodies to the muscle-specific tyrosine kinase (MuSK) to aid in the assessment, monitoring, and management of patients with seronegative myasthenia gravis (MG).

A validated radioimmunoprecipitation assay (RIPA) was used for the measurement of MuSK autoantibodies. Analytical performance including accuracy, precision, linearity, and method agreement was assessed. The assay was cross-validated with a reference RIPA assay using 50 blinded samples. Clinical histories were not known. Analysis of clinical diagnostic data was performed. Over 53,000 clinical sample data were analyzed for positivity rate, antibody titer, and serial measurement patterns.

The MuSK antibody assay had an analytical measurement range (AMR) from 1 – 82 U/mL. Accuracy and precision across the measuring range was <±18% bias and <12% CV. The linear range demonstrated good recovery (90-120%) at each dilution within the AMR. Method agreement was 100% between the two RIPA methods. Of the >53,000 clinical results examined, positivity rate was ~1.3% and 61.1% were classified as low titer (1 – 100 U/mL). The top 5% of samples had high titers above 4500 U/mL, including values >16,400 U/mL. Around 10% of individuals who test positive for MuSK have serial monitoring of titer results.

This study demonstrates a simple and sensitive clinical assay for detecting MuSK antibodies to aid in the diagnosis of MG, disease activity monitoring, and management of patients with AChR antibody-negative MG.