Exploring the role of circulating glial fibrillary acidic protein and neurofilament light chain in myasthenia gravis.

BACKGROUND

Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction caused by antibodies against the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). Although these antibodies enable diagnosis, they correlate poorly with disease activity and prognosis. Emerging data suggest that MG involves broader neuroimmune mechanisms beyond the peripheral synapse. Glial fibrillary acidic protein (GFAP), a marker of astroglial activation, and neurofilament light chain (NfL), a marker of neuroaxonal injury, have been proposed as circulating biomarkers in several neurological diseases. This study aimed to evaluate serum GFAP and NfL concentrations in MG patients and to assess its potential diagnostic utility.

METHODS

In this retrospective case-control study, 137 patients with confirmed MG and 338 healthy controls were enrolled. Clinical classification followed MGFA criteria. Anti-AChR and anti-MuSK antibodies were measured by ELISA. Serum GFAP and NfL concentrations were quantified using a fully automated chemiluminescent immunoassay (Lumipulse G1200). Group comparisons were performed using non-parametric tests, correlations using Spearman analysis, and independent determinants assessed with multivariable linear regression. Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic performance.

RESULTS

Serum GFAP concentrations were higher in MG patients than controls (44.6 vs 29.6 pg/mL) and strongly correlated with age (r = 0.64, p < 0.0001), but not with antibody titers. In multivariable regression, age was the main independent determinant of GFAP (β = 0.00827, p < 0.0001), whereas MG status was not. GFAP showed moderate diagnostic performance (AUC = 0.704). In an age- and sex-matched analysis, NfL concentrations were modestly higher in MG patients compared with controls (30.2 vs 15.5 pg/mL; p = 0.047). A moderate positive correlation between GFAP and NfL was observed in both groups.

CONCLUSIONS

Circulating GFAP levels are elevated in MG but are primarily driven by age and sex rather than disease-specific mechanisms, limiting their diagnostic utility. NfL shows a modest increase, suggesting subtle neuroaxonal involvement; however, its clinical relevance remains uncertain. Together, these findings indicate that GFAP and NfL reflect non-specific neurobiological processes rather than robust biomarkers of MG.