Serum GFAP in multiple sclerosis: correlation with disease type and MRI markers of disease severity

Abstract

Neurofilament light chain (NfL) has been demonstrated to correlate with multiple sclerosis disease severity as well as treatment response. nevertheless, additional serum biomarkers are still needed to better differentiate disease activity from disease progression. The aim of our study was to assess serum glial fibrillary acid protein (s-GFAP) and neurofilament light chain (s-NfL) in a cohort of 129 multiple sclerosis (MS) patients. Eighteen primary progressive multiple sclerosis (PPMS) and 111 relapsing remitting MS (RRMS) were included. We showed that these 2 biomarkers were significantly correlated with each other (R = 0.72, p < 0.001). Moreover, both biomarkers were higher in PPMS than in RRMS even if multivariate analysis only confirmed this difference for s-GFAP (130.3 ± 72.8 pg/ ml vs 83.4 ± 41.1 pg/ml, p = 0.008). Finally, s-GFAP was correlated with white matter lesion load and inversely correlated with WM and GM volume. Our results seem to confirm the added value of s-GFAP in the context of multiple sclerosis. Multiple sclerosis (MS) is a complex autoimmune neurological disease 1. Despite progresses in the management of MS, reliable and easy-to-use biomarkers are needed to accurately identify patients at risk of future disease progression 2. The recent development of highly sensitive immunoassay platforms has enabled the measurement in the serum of several biomarkers of interest in MS. Notably, serum neurofilament light chain (s-NfL) is correlated with disease activity, treatment response, risk of disease progression and MRI markers of disease activity/severity 3-8. Serum Glial Fibrillary Acid Protein (s-GFAP), an intermediate astrocytes cytoskeletal protein, has been only more recently shown to be higher in progressive MS than in RRMS and correlate with disability 9-11 .

Neurofilament light chain as a biomarker for diagnosis of multiple sclerosis

“…A cohort study by Xavier Ayrignac and colleagues evaluated sNFL and s-GFAP levels in 129 MS patients (Ayrignac et al, 2020[ 5 ]). 111 out of 129 patients had PPMS while the other 18 had RRMS.…”

“…However, analysis revealed that the s-GFAP measurements were significantly different. Their results showed that the s-GFAP levels correlated with the white matter lesion load by MRI, but had an inverse correlation with white matter and grey matter volume (Ayrignac et al, 2020[ 5 ]).…”

“…Table 1 (Tab. 1) (References in Table 1: Arrambide et al, 2016[ 4 ]; Ayrignac et al, 2020[ 5 ]; Barro et al, 2018[ 7 ]; Bhan et al, 2018[ 9 ]; Bittner et al, 2020[ 10 ]; Bjornevik et al, 2020[ 11 ]; Dalla Costa et al, 2019[ 20 ]; Disanto et al, 2016[ 23 ], 2017[ 24 ]; Engel et al, 2019[ 26 ]; Gaetani et al, 2019[ 32 ][ 33 ]; Gil-Perotin et al, 2019[ 37 ]; Gunnarsson et al, 2011[ 40 ]; Haghighi et al, 2004[ 41 ]; Håkansson et al, 2017[ 44 ], 2018[ 43 ]; Hendricks et al, 2019[ 48 ]; Jakimovski et al, 2019[ 53 ]; Kuhle et al, 2015[ 59 ], 2016[ 58 ], 2017[ 61 ], 2019[ 60 ]; Lycke et al, 1998[ 64 ]; Malmeström et al, 2003[ 65 ]; Manouchehrinia et al, 2020[ 66 ]; Modvig et al, 2015[ 71 ]; Norgren et al, 2003[ 73 ]; Novakova et al, 2017[ 74 ][ 75 ][ 77 ], 2018[ 76 ]; Olesen et al, 2019[ 78 ]; Panek et al, 2020[ 79 ]; Piehl et al, 2018[ 82 ]; Quintana et al, 2018[ 83 ]; Robinson et al, 2020[ 87 ]; Sejbaek et al, 2019[ 96 ]; Sellebjerg et al, 2019[ 97 ]; Siller et al, 2019[ 98 ]; Thebault et al, 2019[ 104 ]; Tortorella et al, 2018[ 106 ]; van der Vuurst de Vries et al, 2019[ 110 ]; Watanabe et al, 2019[ 112 ]; Wong et al, 2019[ 116 ]; Zhang et al, 2007[ 120 ]) lists various studies that have measured NfL levels in MS patients.…”

Circulating miRNAs as Potential Biomarkers Distinguishing Relapsing–Remitting from Secondary Progressive Multiple Sclerosis. A Review

“…Pasquali et al reported that the plasmatic levels of proinflammatory cytokines, both IFN-γ and IL-17, are higher in RRMS compared to SPMS patients, while the level of transforming growth factor-β (TGF-β), a molecule with immunosuppressant activity, was much lower in RRMS in comparison to SPMS [ 35 ]. Another group of active molecules indicated in the literature are light neurofilaments (NFL) and glial fibrillary acid protein (GFAP), a marker of astrocyte damage and astrogliosis, in serum [ 36 , 37 ]. Högel et al claimed that GFAP and NFL levels in serum are higher in patients with SPMS than RRMS, as well as correlate with a higher EDSS parameter [ 38 ].…”

“…Högel et al claimed that GFAP and NFL levels in serum are higher in patients with SPMS than RRMS, as well as correlate with a higher EDSS parameter [ 38 ]. Whereas Ayrignac et al demonstrated higher levels of both NFL and GFAP in serum from PPMS compared to RRMS, indicating that they might be markers of the disease progression [ 37 ]. Based on the above studies, we consider NFL and GFAP as potential progressive MS and RRMS distinguishing biomarkers.…”