Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis
Author(s)
Type
Journal Article
Abstract
Objective
Intrathecal inflammation, compartmentalized in cerebrospinal fluid (CSF) and in meningeal infiltrates, has fundamental role in inflammation, demyelination, and neuronal injury in cerebral cortex in multiple sclerosis (MS). Since the exact link between intrathecal inflammation and mechanisms of cortical pathology remains unknown, we aimed to investigate a detailed proteomic CSF profiling which is able to reflect cortical damage in early MS.
Methods
We combined new proteomic method, TRIDENT, CSF analysis, and advanced 3T magnetic resonance imaging (MRI), in 64 MS patients at the time of diagnosis and 26 controls with other neurological disorders. MS patients were stratified according to cortical lesion (CL) load.
Results
We identified 227 proteins differently expressed between the patients with high and low CL load. These were mainly related to complement and coagulation cascade as well as to iron homeostasis pathway (30 and 6% of all identified proteins, respectively). Accordingly, in the CSF of MS patients with high CL load at diagnosis, significantly higher levels of sCD163 (P < 0.0001), free hemoglobin (Hb) (P < 0.05), haptoglobin (P < 0.0001), and fibrinogen (P < 0.01) were detected. By contrast, CSF levels of sCD14 were significantly (P < 0.05) higher in MS patients with low CL load. Furthermore, CSF levels of sCD163 positively correlated (P < 0.01) with CSF levels of neurofilament, fibrinogen, and B cell‐related molecules, such as CXCL13, CXCL12, IL10, and BAFF.
Interpretation
Intrathecal dysregulation of iron homeostasis and coagulation pathway as well as B‐cell and monocyte activity are strictly correlated with cortical damage at early disease stages.
Intrathecal inflammation, compartmentalized in cerebrospinal fluid (CSF) and in meningeal infiltrates, has fundamental role in inflammation, demyelination, and neuronal injury in cerebral cortex in multiple sclerosis (MS). Since the exact link between intrathecal inflammation and mechanisms of cortical pathology remains unknown, we aimed to investigate a detailed proteomic CSF profiling which is able to reflect cortical damage in early MS.
Methods
We combined new proteomic method, TRIDENT, CSF analysis, and advanced 3T magnetic resonance imaging (MRI), in 64 MS patients at the time of diagnosis and 26 controls with other neurological disorders. MS patients were stratified according to cortical lesion (CL) load.
Results
We identified 227 proteins differently expressed between the patients with high and low CL load. These were mainly related to complement and coagulation cascade as well as to iron homeostasis pathway (30 and 6% of all identified proteins, respectively). Accordingly, in the CSF of MS patients with high CL load at diagnosis, significantly higher levels of sCD163 (P < 0.0001), free hemoglobin (Hb) (P < 0.05), haptoglobin (P < 0.0001), and fibrinogen (P < 0.01) were detected. By contrast, CSF levels of sCD14 were significantly (P < 0.05) higher in MS patients with low CL load. Furthermore, CSF levels of sCD163 positively correlated (P < 0.01) with CSF levels of neurofilament, fibrinogen, and B cell‐related molecules, such as CXCL13, CXCL12, IL10, and BAFF.
Interpretation
Intrathecal dysregulation of iron homeostasis and coagulation pathway as well as B‐cell and monocyte activity are strictly correlated with cortical damage at early disease stages.
Date Issued
2019-11-01
Date Acceptance
2019-08-12
Citation
Annals of Clinical and Translational Neurology, 2019, 6 (11), pp.2150-2163
ISSN
2328-9503
Publisher
Wiley Open Access
Start Page
2150
End Page
2163
Journal / Book Title
Annals of Clinical and Translational Neurology
Volume
6
Issue
11
Copyright Statement
© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000493574100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Neurosciences & Neurology
BRAIN-BARRIER DISRUPTION
CEREBROSPINAL-FLUID
B-CELLS
MENINGEAL INFLAMMATION
HEMOGLOBIN
DEMYELINATION
FIBRINOGEN
PROTEIN
IDENTIFICATION
WIDESPREAD
Publication Status
Published
Date Publish Online
2019-11-01