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GFAP, CHI3L1 and GCIPL Thickness as Baseline Predictors of Early Disability Progression in MS
Ion Iulian Enache1,2, Vlad Eugen Tiu2,3, Cătălina Andreea Anghel3
1Neurology Department, Emergency University Hospital Bucharest, Splaiul Independenței 169, 050098 Bucharest, Romania.
International Journal of Molecular Sciences
|December 30, 2025
Summary
Biomarkers in cerebrospinal fluid (CSF) and optical coherence tomography (OCT) can predict early disability progression in relapsing-remitting multiple sclerosis (RRMS). Elevated CSF GFAP, CSF CHI3L1, and reduced GCIPL thickness are key indicators for predicting MS worsening.
Area of Science:
- Neurology
- Biomarkers
- Neuroimmunology
Background:
- Disability accumulation in multiple sclerosis (MS) often occurs independently of relapses and inflammation.
- Predicting early disability progression in newly diagnosed relapsing-remitting MS (RRMS) remains challenging.
- Identifying reliable early predictors is crucial for timely intervention and management.
Purpose of the Study:
- To evaluate the utility of baseline fluid and optical coherence tomography (OCT) biomarkers for predicting early disability progression in newly diagnosed RRMS patients.
- To assess the predictive value of specific biomarkers including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and chitinase-3-like protein 1 (CHI3L1) in serum and cerebrospinal fluid (CSF).
- To determine the association between retinal layer thickness measured by OCT and 1-year confirmed disability progression (1yCDP).
Main Methods:
- A monocentric observational cohort study involving 72 newly diagnosed RRMS patients followed for 2 years.
- Baseline serum and CSF samples were analyzed for NfL, GFAP, and CHI3L1 levels.
- Confirmed disability progression at 1 year (1yCDP) was defined by changes in the Expanded Disability Status Scale (EDSS) or functional tests (Nine-Hole Peg Test, Timed 25-Foot Walk).
- OCT was used to measure retinal layer thickness, including the ganglion cell-inner plexiform layer (GCIPL).
Main Results:
- Seventeen patients (23.6%) experienced 1yCDP.
- Elevated baseline CSF GFAP (OR=5.79, p=0.005) and CSF CHI3L1 (OR=4.14, p=0.006) independently predicted 1yCDP.
- Reduced GCIPL thickness (OR=0.90, p=0.006) also independently predicted 1yCDP.
- A multivariate model incorporating age, CSF GFAP, and GCIPL thickness achieved an AUC of 0.831, with 87.5% sensitivity and 61.5% specificity.
Conclusions:
- Baseline profiling using CSF GFAP, CSF CHI3L1, and GCIPL thickness can effectively predict early disability progression in RRMS patients.
- These biomarkers offer valuable insights into disease activity and progression beyond inflammatory markers.
- This approach may aid in identifying patients at higher risk for early progression, enabling personalized treatment strategies.
