GFAP, CHI3L1 and GCIPL Thickness as Baseline Predictors of Early Disability Progression in MS

Disability accumulation in multiple sclerosis often occurs independent of relapses and inflammatory activity, yet reliable predictors for early progression remain limited. Our aim was to evaluate the utility of baseline fluid and optical coherence tomography (OCT) biomarkers for predicting early disability progression in newly diagnosed relapsing-remitting MS (RRMS). We performed a monocentric observational cohort study on 72 RRMS patients that were enrolled within 6 months of diagnosis and followed for 2 years. Baseline serum and cerebrospinal fluid (CSF) samples were analyzed for neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and chitinase-3-like protein 1 (CHI3L1). Confirmed disability progression at 1 year (1yCDP) was defined by either an increase in Expanded Disability Status Scale or a ≥20% worsening on Nine-Hole Peg Test or Timed 25-Foot Walk. Seventeen patients (23.6%) developed 1yCDP. Elevated baseline CSF GFAP (OR = 5.79, 95% CI 1.72-19.45; p = 0.005) and CSF CHI3L1 thickness (OR = 4.14, 95% CI 1.49-11.49; p = 0.006) and reduced ganglion cell-inner plexiform layer (GCIPL) thickness (OR = 0.90, 95% CI 0.84-0.97; p = 0.006) independently predicted 1yCDP. A multivariate model including age, CSF GFAP and GCIPL achieved AUC = 0.831, with a sensitivity of 87.5% and specificity of 61.5%. This study provides evidence that baseline patient profiling using CSF GFAP, CSF CHI3L1 and GCIPL thickness may help predict early disability progression in RRMS.