Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis

Abstract

Objective:To investigate glial and neuronal biomarkers in cerebrospinal fluid (CSF) samples from patients with relapsing–remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS), and to evaluate their ability to predict conversion from CIS to clinically definite MS (CDMS) and also disability progression in MS.Methods:CSF levels of neurofilament light protein (NFL), t-tau, p-tau, glial fibrillary acidic protein (GFAP), S-100B, human chitinase 3-like 1 protein (YKL-40), monocyte chemoattractant protein-1 (MCP-1), α-sAPP and β-sAPP; and Aβ38, Aβ40 and Aβ42, were analyzed in 109 CIS patients and 192 RRMS patients. The mean follow-up time of these 301 patients was 11.7 ± 6.4 years.Results:High levels of NFL were associated with early conversion from CIS to CDMS (hazard ratio (HR) with 95% confidence interval (CI): 2.69 (1.75 – 4.15); p < 0.0001). High levels of YKL-40 and GFAP were associated with earlier progression in the Expanded Disability Status Scale (EDSS), score 3: YKL-40 (HR (95% CI): 2.78 (1.48 – 5.23); p = 0.001) and GFAP (HR (95% CI): 1.83 (1.01 – 3.35); p = 0.04). High levels of YKL-40 were associated with earlier progression to EDSS 6 (HR (95% CI): 4.57 (1.01 – 20.83); p = 0.05).Conclusions:CSF levels of NFL in CIS patients are an independent prognostic marker for conversion to CDMS. Whereas, CSF levels of YKL-40 and GFAP are independent prognostic markers for disability progression in MS.

CHIT1 at Diagnosis Reflects Long‐Term Multiple Sclerosis Disease Activity

“…Only 1 previous study considered CHIT1 in the context of prognosis in MS but was limited in terms of a smaller study population and of sampling patients with an indication to switch therapies at different time points in disease instead of newly diagnosed patients . Baseline (diagnostic stage) CSF CHI3L1 levels have been associated with earlier progression to disability . There is a similar trend in our study, but we demonstrated this to be secondary to the substantially stronger association with CHIT1.…”

Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing–remitting multiple sclerosis

“…NFL levels did not differ between patients in relapse and patients not in relapse at the time of CSF collection in our study. Data on NFL levels in relation to relapse status in other studies are inconsistent , possibly because of differences in sample size and patient selection. Our finding of similar levels of NFL irrespective of relapse implies a positive quality as a clinical biomarker.…”

Transcriptome sequencing of neurologic diseases associated genes in HHV-6A infected human astrocyte

“…Significant expression differences of SERPINA1 (AAT) were identified as potential disease signatures for MS patients [95] and elevates in the cerebrospinal fluid of patients with MS [96]. CXCL16 could be a novel biomarker and potential predictor of disease activity in MS [97]. IFITM3 leads to neuropathological impairments and brain dysfunction in astrocytes [98].…”