Please use this identifier to cite or link to this item:
https://hdl.handle.net/10356/153838
Title: | Changes in cerebrospinal fluid balance of TNF and TNF receptors in naïve multiple sclerosis patients : early involvement in compartmentalised intrathecal inflammation | Authors: | Magliozzi, Roberta Pezzini, Francesco Pucci, Mairi Rossi, Stefania Facchiano, Francesco Marastoni, Damiano Montagnana, Martina Lippi, Giuseppe Reynolds, Richard Calabrese, Massimiliano |
Keywords: | Science::Medicine | Issue Date: | 2021 | Source: | Magliozzi, R., Pezzini, F., Pucci, M., Rossi, S., Facchiano, F., Marastoni, D., Montagnana, M., Lippi, G., Reynolds, R. & Calabrese, M. (2021). Changes in cerebrospinal fluid balance of TNF and TNF receptors in naïve multiple sclerosis patients : early involvement in compartmentalised intrathecal inflammation. Cells, 10(7), 1712-. https://dx.doi.org/10.3390/cells10071712 | Journal: | Cells | Abstract: | An imbalance of TNF signalling in the inflammatory milieu generated by meningeal immune cell infiltrates in the subarachnoid space in multiple sclerosis (MS), and its animal model may lead to increased cortical pathology. In order to explore whether this feature may be present from the early stages of MS and may be associated with the clinical outcome, the protein levels of TNF, sTNF-R1 and sTNF-R2 were assayed in CSF collected from 122 treatment-naïve MS patients and 36 subjects with other neurological conditions at diagnosis. Potential correlations with other CSF cytokines/chemokines and with clinical and imaging parameters at diagnosis (T0) and after 2 years of follow-up (T24) were evaluated. Significantly increased levels of TNF (fold change: 7.739; p < 0.001), sTNF-R1 (fold change: 1.693; p < 0.001) and sTNF-R2 (fold change: 2.189; p < 0.001) were detected in CSF of MS patients compared to the control group at T0. Increased TNF levels in CSF were significantly (p < 0.01) associated with increased EDSS change (r = 0.43), relapses (r = 0.48) and the appearance of white matter lesions (r = 0.49). CSF levels of TNFR1 were associated with cortical lesion volume (r = 0.41) at T0, as well as with new cortical lesions (r = 0.56), whilst no correlation could be found between TNFR2 levels in CSF and clinical or MRI features. Combined correlation and pathway analysis (ingenuity) of the CSF protein pattern associated with TNF expression (encompassing elevated levels of BAFF, IFN-γ, IL-1β, IL-10, IL-8, IL-16, CCL21, haptoglobin and fibrinogen) showed a particular relationship to the interaction between innate and adaptive immune response. The CSF sTNF-R1-associated pattern (encompassing high levels of CXCL13, TWEAK, LIGHT, IL-35, osteopontin, pentraxin-3, sCD163 and chitinase-3-L1) was mainly related to altered T cell and B cell signalling. Finally, the CSF TNFR2-associated pattern (encompassing high CSF levels of IFN-β, IFN-λ2, sIL-6Rα) was linked to Th cell differentiation and regulatory cytokine signalling. In conclusion, dysregulation of TNF and TNF-R1/2 pathways associates with specific clinical/MRI profiles and can be identified at a very early stage in MS patients, at the time of diagnosis, contributing to the prediction of the disease outcome. | URI: | https://hdl.handle.net/10356/153838 | ISSN: | 2073-4409 | DOI: | 10.3390/cells10071712 | Schools: | Lee Kong Chian School of Medicine (LKCMedicine) | Rights: | © 2021 The Author(s). Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | LKCMedicine Journal Articles |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
cells-10-01712-v2.pdf | 2.63 MB | Adobe PDF | ![]() View/Open |
SCOPUSTM
Citations
20
17
Updated on Feb 12, 2025
Web of ScienceTM
Citations
20
7
Updated on Oct 29, 2023
Page view(s)
136
Updated on Feb 15, 2025
Download(s) 50
92
Updated on Feb 15, 2025
Google ScholarTM
Check
Altmetric
Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.