Serum GFAP as a biomarker for disease severity in multiple sclerosis

Abstract

While neurofilament light chain (NfL) measurement in serum is a well-established marker of neuroaxonal damage in multiple sclerosis (MS), data on astroglial markers in serum are missing. In our study, glial fibrillary acid protein (GFAP) and NfL were measured in cerebrospinal fluid (CSF) and serum of MS patients and patients with other non-inflammatory neurological diseases (OND) using the Simoa technology. Clinical data like age, gender, expanded disability status scale (EDSS) and MRI findings were correlated to neurochemical markers. We included 80 MS patients: 42 relapsing-remitting MS (RRMS), 38 progressive MS (PMS), as well as 20 OND. Serum GFAP levels were higher in PMS compared to RRMS and OND (p < 0.001, p = 0.02 respectively). Serum GFAP levels correlated with disease severity in the whole MS group and PMS (Spearman-rho = 0.5, p < 0.001 in both groups). Serum GFAP correlated with serum NfL in PMS patients (Spearman-rho = 0.4, p = 0.01). Levels of serum GFAP were higher with increasing MRI-lesion count (p = 0.01). in summary, we report elevated levels of GFAP in the serum of MS patients. Since serum levels of GFAP correlate with the clinical severity scores and MRI lesion count, especially in PMS patients, it might be a suitable disease progression marker.

Figure 1

GFAP CSF and serum levels in multiple sclerosis patients and patients with other non-inflammatory neurological diseases (OND). GFAP: glial fibrillary acidic protein. CSF: cerebrospinal fluid, PMS: progressive multiple sclerosis, RRMS: relapsing-remitting multiple sclerosis. P-values were calculated with Kruskal-Wallis test followed by Dunn’s multiple comparison tests. ^*p < 0.05; ^***p < 0.001.

Figure 2

Spearman correlation (rho) between serum glial fibrillary acidic protein (GFAP) and expanded disability status scale (EDSS) in the whole multiple sclerosis (MS), progressive (PMS) and primary progressive (PPMS) patients. ^**p < 0.01, ^***p < 0.001.

Figure 3

NfL CSF and serum levels in multiple sclerosis patients and patients with other non-inflammatory neurological diseases (OND). NfL: neurofilament light chain, CSF: cerebrospinal fluid, PMS: progressive multiple sclerosis, RRMS: relapsing-remitting multiple sclerosis. OND: other non-inflammatory neurological diseases. P-values were calculated with Kruskal-Wallis test followed by Dunn’s multiple comparison test. ^***p < 0.001.

Figure 4

Spearman correlation (rho) between glial fibrillary acidic protein (GFAP) and neurofilaments light (NfL) in cerebrospinal fluid (CSF) and serum in the whole multiple sclerosis (MS), progressive (PMS) and primary progressive (PPMS) patients. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001.

Figure 5

Quotient of glial fibrillary acidic protein (GFAP) and neurofilaments light (NfL) in cerebrospinal fluid (CSF) and serum in progressive multiple sclerosis patients (PMS) compared to relapsing-remitting multiple sclerosis (RRMS). n.s.: not significant.