Circulating GFAP and Neurofilament Light Chain in Myasthenia Gravis: A Preliminary Exploratory Case Series
Aurora Zanghì, Paola Sofia Di Filippo, Emanuele D’AmicoIntroduction:
Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are circulating biomarkers reflecting astroglial activation and axonal injury. While these markers have been extensively investigated in neurodegenerative and neuroinflammatory diseases, their relevance in autoimmune neuromuscular disorders such as myasthenia gravis (MG) remains unclear.
Methods:
A preliminary, exploratory, cross-sectional case series of 7 patients with confirmed MG was conducted. Serum GFAP and NfL concentrations were measured using ultrasensitive assays. Within-cohort relationships between biomarkers, clinical severity scores, and age were summarized using Spearman correlation analysis and exploratory age-adjusted linear models, interpreted descriptively rather than as confirmatory hypothesis tests. Individual biomarker values were also benchmarked descriptively against published age-stratified serum upper reference limits derived from healthy adults.
Results:
In this cohort, GFAP and NfL levels showed a high positive within-cohort correlation (p = 0.93, p = 0.002). No clear relationship with the MG Activities of Daily Living scale or Quantitative MG clinical scores was observed, although the sample size precludes exclusion of clinically meaningful associations. Age showed positive associations with both GFAP (β = 0.51, p = 0.039) and NfL levels (β = 0.56, p = 0.049), consistent with the known age dependence of these biomarkers. Compared with the published external age-stratified limits, GFAP was below the relevant threshold in all seven participants, whereas NfL exceeded it in four of seven (57.1%); among the four participants within the 18-69-year age range, two exceeded the NfL limit.
Discussion:
In this preliminary exploratory cohort of patients with MG, circulating GFAP and NfL showed a high within-cohort correlation. Because of the very small sample size, absence of controls, and heterogeneous treatment exposure, these findings should be interpreted as descriptive and hypothesis-generating. External benchmarking showed a discordant descriptive pattern for NfL and GFAP, but it cannot establish MG-specific biomarker abnormality because the reference cohort was not assay-matched and 3 participants were outside its age range.
Conclusion:
Simultaneous measurement of serum GFAP and NfL was feasible in this small MG cohort. Larger, controlled, longitudinal studies are required to determine whether these biomarkers provide disease-specific or clinically meaningful information in MG. The external benchmark was descriptive only and requires confirmation using contemporaneous age-matched controls and an assay-matched platform.