Blood glial fibrillary acidic protein in patients with multiple sclerosis: a systematic review and meta-analysis

Emerging evidence suggests that Glial fibrillary acidic protein (GFAP) may help track disease activity and progression in multiple sclerosis (MS), particularly in distinguishing between relapsing and progressive forms. This study aims to systematically assess blood GFAP levels in MS patients compared to healthy controls and across different MS subtypes. We systematically searched PubMed and Web of Science up to February 20, 2025, for studies reporting blood GFAP levels in patients with MS and controls. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Effect sizes were calculated using Hedges’ g. A random effects model was applied when heterogeneity was significant (I² > 50%), and a fixed effects model otherwise. Heterogeneity was assessed using the I² statistic, and publication bias was evaluated through funnel plots and Egger’s and Begg’s tests. From 581 records, 20 studies with a total of 2,808 participants were included. Blood GFAP levels were significantly higher in MS patients compared to controls (SMD = 0.94; 95% CI [0.62, 1.25]; I² = 92.15%; p < 0.001). We also found elevated GFAP levels in all major MS subtypes: relapsing-remitting MS (RRMS) (SMD = 0.76; 95% CI [0.36, 1.16]; I² = 91.12%; p < 0.001), SPMS (SMD = 0.76; 95% CI [0.53, 0.98]; I² = 0.00%; p < 0.001), PPMS (SMD = 1.55; 95% CI [0.11, 2.29]; I² = 96.57%; p = 0.03), and combined PMS (SMD = 1.12; 95% CI [0.49, 1.75]; I² = 94.41%; p < 0.001) compared to controls. Additionally, GFAP levels were significantly higher in PMS than in RRMS (SMD = 0.64; 95% CI [0.34, 0.94]; I² = 78.19%; p < 0.001). Our findings suggest that blood GFAP may serve as a supportive biomarker for disease progression and subtype monitoring in MS. Given its non-specific nature and interindividual variability, its greatest clinical potential may lie in longitudinal assessment rather than single-time-point diagnostics. Further studies are needed to validate its use alongside established tools for tracking disease activity and therapeutic outcomes.