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.
Highlights
The pathophysiology of multiple sclerosis (MS) is a complex interplay of B and T lymphocytes, demyelination, and axonal demise [1]
chitinase-3-like protein 1 (CHI3L1) levels were higher in PMS patients compared to relapsing–remitting MS (RRMS) in the cerebrospinal fluid (CSF) and in serum
The calculated Glia score showed significantly higher levels in PMS patients compared to RRMS patients in the CSF and in serum
Summary
The pathophysiology of multiple sclerosis (MS) is a complex interplay of B and T lymphocytes, demyelination, and axonal demise [1]. The most extensively investigated marker for axonal damage is neurofilament light chain (NfL), which was shown to be elevated in the cerebrospinal fluid (CSF) of MS patients, correlating with MRI parameters of patients and being a potential prognostic biomarker [8,9,10,11]. A further marker for glial activation, especially microglial activation, chitinase-3-like protein 1 (CHI3L1), was shown to be elevated in the CSF of MS patients compared to controls and a putative prognostic biomarker in patients with a clinically isolated syndrome (CIS) [14,15,16,17,18]. 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
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