Serum utrophin levels in patients with myasthenia gravis: an exploratory study

The role of utrophin, a protein expressed at neuromuscular junctions, remains unclear in myasthenia gravis (MG). This study aimed to investigate serum utrophin levels in immunotherapy-naïve patients with different MG subtypes and evaluate changes before and after immunotherapy initiation.

We measured serum utrophin levels in immunotherapy-naïve MG patients (n = 39), including acetylcholine receptor (AChR) antibody-positive MG (AChR-MG) (n = 30; ocular type: n = 10, generalized type: n = 20) and muscle-specific tyrosine kinase antibody-positive MG (MuSK-MG) (n = 9; all generalized type) patients and healthy controls (HCs) (n = 21). We analyzed relationships between serum utrophin levels, clinical parameters, and antibody levels. In generalized AChR-MG, serum utrophin levels were measured before and after immunotherapy.

Median serum utrophin levels tended to be higher in patients with MG than in HCs (34.0 vs. 13.8 ng/mL; Hodges-Lehmann estimate, 7.04 ng/mL; 95% confidence interval: -0.09-37.3; p = 0.051). In MuSK-MG, an exploratory positive correlation with the MG Foundation of America (MGFA) classification was observed (ρ = 0.69, nominal p = 0.041). In generalized AChR-MG, median concentrations numerically decreased from 43.8 to 20.2 ng/mL after immunotherapy (p = 0.064), but no significant change was observed in the 15 patients whose paired samples were both within the standard range (p = 0.80).

These exploratory findings suggest that circulating utrophin may reflect disease-related biological changes in MG, although definitive conclusions regarding its biomarker utility cannot be drawn. Further validation in larger cohorts using analytically validated assays is warranted.