A candidate biomarker of glial fibrillary acidic protein in CSF and blood in differentiating multiple sclerosis and its subtypes: A systematic review and meta-analysis

Abstract

Objective: Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease of the central nervous system. Glial fibrillary acidic protein (GFAP) is a monomeric intermediate filament protein. A systematic review and meta-analysis was performed regarding a candidate biomarker for astrocytic damage of cerebrospinal fluid (CSF) and blood GFAP levels in differentiating multiple sclerosis and its subtypes.

Methods: Relevant studies published prior to October 2020 were retrieved from the PubMed, Web of Science, Cochrane Library and clinicaltrials.gov databases using the following keywords: 'Multiple sclerosis' or 'MS' and 'Glial Fibrillary Acidic Protein' or 'GFAP'. Two authors independently selected the articles and extracted the data. Of the 31 full articles screened, 11 were included in the qualitative analysis and meta-analysis. Differences in the mean CSF and blood GFAP levels were used as the main efficacy measures, and the meta-analysis was performed using Review Manager version 5.3 software.

Results: Eleven clinical trials comprising 960 patients were selected. CSF GFAP levels were higher in 503 MS patients than in 252 (healthy and disease) controls, with a moderate effect size of 0.72 (p < 0.00001). Mean CSF GFAP levels were significantly higher in 325 MS patients with relapsing disease than in 140 MS patients with progressive disease (SMD=-0.47; 95% CI=-0.80 to -0.15; P = 0.005). CSF GFAP levels in 161 MS patients in relapse (irrespective of MS subtype) were significantly higher than those in 180 MS patients in remission (MD=103.83; 95% CI=68.09 to139.57; P<0.001). The performances of GFAP in blood for differentiating patients with MS from controls were also significant. Blood GFAP was higher in 245 MS patients than in 53 (healthy and disease) controls, with a moderate effect size of 37.25 (p < 0.00001).

Conclusion: The level of CSF-GFAP is correlated with MS and its different subtypes, reflecting the different degrees of damage to astrocytes in different subtypes of MS. In addition, progressive MS is more closely related to the increase in cerebrospinal fluid GFAP level than relapsing-remitting MS, and GFAP may be a useful marker of disease progression. Moreover, the GFAP level in the blood of MS patients is higher than that in the control group, and the sample size needs to be further expanded for verification in the future..

Keywords: Glial fibrillary acidic protein; Meta-analysis; Multiple sclerosis; Systematic review.