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Updated: Jun 14, 2025

Author Spotlight: Unveiling the Pathway Linking Obesity to Autoimmune Inflammation in Multiple Sclerosis
Published on: February 23, 2024
Serum glial fibrillary acidic protein predicts disease progression in multiple sclerosis
Evan Madill1,2, Brian C Healy1,2, Negar Molazadeh1
1Brigham Multiple Sclerosis Center, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Objective:
Glial fibrillary acidic protein (GFAP) is expressed in astrocytes and may be a useful marker of non-active progressive multiple sclerosis (MS). We evaluate serum GFAP (sGFAP) in a large cohort of MS patients to determine if it predicts progression independent of relapse activity (PIRA), future gait aid, and conversion to secondary progressive disease (SPMS).
Methods:
Adults with clinically isolated syndrome or any subtype of MS who were listed in the Brigham MS Center Research Database and had at least one sGFAP result were included. All clinic visits following first sample were analyzed for PIRA, future gait aid, and conversion to SPMS. Future cognitive dysfunction and fatigue were evaluated as secondary outcomes.
Results:
In total, 741 patients were included (average age: 42.3, average disease duration: 3.7 years, median EDSS: 2, and median follow-up duration: 10.0 years). Of 643 patients (86.8%) without progressive disease at baseline, 15.9% developed SPMS. Among all 741, 50.5% had PIRA and 18.6% developed a gait aid requirement. sGFAP level predicted PIRA, future gait aid, and conversion to SPMS in univariable models (p < 0.001, <0.001, and 0.002). sGFAP remained predictive for PIRA and future gait aid in multivariable models in those younger than 50 (p = 0.048, 0.003). Change in sGFAP level over time was not predictive. There was no association between sGFAP and future fatigue or cognitive dysfunction.
Interpretation:
sGFAP helps to predict PIRA, future gait aid, and conversion to SPMS in a large cohort of MS patients. Our data suggest that baseline levels may be more useful than the change over time.
Insights
Serum glial fibrillary acidic protein (sGFAP) levels can predict multiple sclerosis (MS) progression, including progression independent of relapse activity (PIRA) and future disability. Baseline sGFAP levels appear more valuable than changes over time for predicting MS outcomes.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Clinical Neurology
Background:
- Glial fibrillary acidic protein (GFAP) is an astrocyte marker.
- Elevated GFAP may indicate active central nervous system damage.
- Its utility in predicting multiple sclerosis (MS) progression requires further investigation.
Purpose of the Study:
- To evaluate serum GFAP (sGFAP) as a predictor of disease progression in a large cohort of MS patients.
- To determine if sGFAP predicts progression independent of relapse activity (PIRA), future gait aid use, and conversion to secondary progressive MS (SPMS).
Main Methods:
- Analysis of sGFAP levels in 741 adult MS patients from the Brigham MS Center Research Database.
- Longitudinal assessment of clinical outcomes including PIRA, gait aid requirement, and SPMS conversion.
- Evaluation of cognitive dysfunction and fatigue as secondary outcomes.
Main Results:
- sGFAP levels significantly predicted PIRA, future gait aid use, and SPMS conversion in univariable analyses.
- sGFAP remained a significant predictor for PIRA and gait aid in multivariable models for patients under 50.
- No association was found between sGFAP and future fatigue or cognitive dysfunction.
Conclusions:
- Baseline sGFAP levels are a valuable biomarker for predicting key aspects of MS progression, including PIRA and disability.
- sGFAP aids in identifying patients at higher risk for worsening disability and disease advancement.
- The predictive value of sGFAP in MS appears to be linked to baseline levels rather than changes over time.
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