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. 2020 Jul 16:11:608.
doi: 10.3389/fneur.2020.00608. eCollection 2020.

A Score Based on NfL and Glial Markers May Differentiate Between Relapsing-Remitting and Progressive MS Course

André Huss  1 , Markus Otto  1 , Makbule Senel  1 , Albert C Ludolph  1 , Ahmed Abdelhak  1   2 , Hayrettin Tumani  1   3
Affiliations

A Score Based on NfL and Glial Markers May Differentiate Between Relapsing-Remitting and Progressive MS Course

André Huss et al. Front Neurol. .

Abstract

Background: The diagnostic use of biomarkers in body fluids of multiple sclerosis (MS) patients allows the monitoring of different pathophysiological aspects of the disease. We previously reported elevated cerebrospinal fluid (CSF) and serum levels of glial fibrillary acidic protein (GFAP) but not neurofilament light chain (NfL) in progressive (PMS) compared to relapsing-remitting MS (RRMS) patients. Objectives: We analyzed the glial marker chitinase-3-like protein 1 (CHI3L1) in the CSF and serum of PMS and RRMS patients. To capture the extent of glial processes in relation to axonal damage in each individual patient, we established a score based on CHI3L1, GFAP, and NfL and compared this score between RRMS and PMS patients and its association with the extended disability status scale (EDSS). Methods: For this retrospective study, we included 86 MS patients (47 RRMS and 39 PMS) and 20 patients with other non-inflammatory neurological diseases (OND) as controls. NfL and GFAP levels were determined by the single-molecule array (Simoa). CHI3L1 levels were measured with classical enzyme-linked immunosorbent assay. A score was calculated based on glial to axonal markers (CHI3L1*GFAP/NfL, referred to as "Glia score"). Results: CHI3L1 showed higher CSF levels in PMS vs. RRMS and controls (p < 0.001 and p < 0.0001, respectively), RMS vs. controls (p < 0.01), and higher serum levels for PMS vs. RRMS (p < 0.05). The Glia score was higher in the CSF of PMS compared to RRMS patients (p < 0.0001) and in the serum of PMS patients compared to RRMS (p < 0.01). Furthermore, the Glia score and CHI3L1 in serum but not in CSF correlated with the disability as determined by EDSS in the PMS group but not in the RRMS group (Spearman ρ = 0.46 and 0.45, p = 0.003 and 0.004, respectively). Discussion: Our data indicate the involvement of glial mechanisms during the pathogenesis of PMS. Moreover, a calculated score may help to differentiate between PMS and RMS in the CSF and monitor disease progression in the serum of PMS patients.

Keywords: CSF; glial markers; multiple sclerosis; neurofilament light chain; progressive MS; serum.

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Figures

Figure 1
Figure 1
Chitinase-3-like protein 1 (CHI3L1) levels in cerebrospinal fluid (CSF) and serum of progressive multiple sclerosis (PMS) and relapsing–remitting MS (RRMS) patients. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.
Figure 2
Figure 2
Glia score in the cerebrospinal fluid (CSF) of progressive multiple sclerosis (PMS) and relapsing–remitting MS (RRMS) patients. ****p < 0.0001.
Figure 3
Figure 3
Glia score in the serum of progressive multiple sclerosis (PMS) and relapsing–remitting MS (RRMS) patients. **p < 0.01.
Figure 4
Figure 4
Receiver operating characteristics (ROC) analyses of Glia score (diamonds), CHI3L1 (triangle down), glial fibrillary acidic protein (GFAP) (square), and neurofilament light chain (NfL) (triangle up) in the cerebrospinal fluid (CSF) and for the comparison of progressive multiple sclerosis (PMS) vs. relapsing MS (RMS) patients. AUC, area under the curve.
Figure 5
Figure 5
Receiver operating characteristics (ROC) analyses of Glia score (diamonds), CHI3L1 (triangle down), glial fibrillary acidic protein (GFAP) (square), and neurofilament light chain (NfL) (triangle up) in the serum and for the comparison of progressive multiple sclerosis (PMS) vs. relapsing MS (RMS) patients. AUC, area under the curve.
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References

    1. Compston A, Coles A. Multiple sclerosis. Lancet. (2002) 359:1221–31. 10.1016/S0140-6736(02)08220-X - DOI - PubMed
    1. Kuhlmann T, Lingfeld G, Bitsch A, Schuchardt J, Brück W. Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain. (2002) 125:2202–12. 10.1093/brain/awf235 - DOI - PubMed
    1. Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol. (2015) 14:183–93. 10.1016/S1474-4422(14)70256-X - DOI - PubMed
    1. Lassmann H, van Horssen J, Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol. (2012) 8:647–56. 10.1038/nrneurol.2012.168 - DOI - PubMed
    1. Lassmann H. Mechanisms of white matter damage in multiple sclerosis. Glia. (2014) 62:1816–30. 10.1002/glia.22597 - DOI - PubMed