Abstract
Background and Objectives To evaluate the extent of intrathecal inflammation in patients with primary progressive MS (PPMS) at the time of diagnosis and to define markers and a specific inflammatory profile capable of distinguishing progressive from relapsing-remitting multiple sclerosis (RRMS).
Methods Levels of 34 pro- and anti-inflammatory cytokines and chemokines in the CSF were evaluated at the diagnosis in 16 patients with PPMS and 80 with RRMS. All patients underwent clinical evaluation, including Expanded Disability Status Scale assessment and a 3T brain MRI to detect white matter and cortical lesion number and volume and global and regional cortical thickness.
Results Higher levels of CXCL12 (odds ratio [OR] = 3.97, 95% CI [1.34–11.7]) and the monocyte-related osteopontin (OR = 2.24, 95% CI [1.01–4.99]) were detected in patients with PPMS, whereas levels of interleukin-10 (IL10) (OR = 0.28, 95% CI [0.09–0.96]) were significantly increased in those with RRMS. High CXCL12 levels were detected in patients with increased gray matter lesion number and volume (p = 0.001, r = 0.832 and r = 0.821, respectively). Pathway analysis confirmed the chronic inflammatory processes occurring in PPMS.
Conclusions At the time of diagnosis, a specific CSF protein profile can recognize the presence of early intrathecal inflammatory processes, possibly stratifying PPMS with respect to RRMS. Elevated CSF levels of CXCL12 and osteopontin suggested a key role of brain innate immunity and glia activity in MS. These molecules could represent useful candidate markers of MS progression, with implications for the pathogenesis and treatment of progressive MS.
Classification of Evidence This study provides Class III evidence that CXCL12 and monocyte-related osteopontin may be correlated with PPMS, and IL-10 may be related to RRMS. It is may be correlated due to Bonferroni correction negating the statistical correlations found in the study.
Glossary
- BAFF=
- B-cell activating factor;
- CCL=
- chemokine (C-C motif) ligand;
- CTh=
- cortical thickness;
- CXCL=
- chemokine (C-X-C motif) ligand;
- DIR=
- double inversion recovery;
- EDSS=
- Expanded Disability Status Scale;
- IgG=
- immunoglobulin G;
- IL=
- interleukin;
- MIPAV=
- Medical Image Processing and Visualization;
- MMP=
- matrix metallopeptidase;
- MS=
- multiple sclerosis;
- OR=
- odds ratio;
- PPMS=
- primary progressive MS;
- RRMS=
- relapsing-remitting MS;
- SPMS=
- secondary progressive MS;
- sTNFR=
- soluble TNF receptor;
- TE=
- echo time;
- TI=
- inversion time;
- TNF=
- tumor necrosis factor;
- TR=
- repetition time;
- TSE=
- turbo spin echo;
- TWEAK=
- TNF-related weak inducer of apoptosis;
- VIF=
- variance inflation factor;
- WM=
- white matter;
- WMLV=
- WM lesion volume
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors have contributed equally to this work and share first authorship.
The Article Processing Charge was funded by the authors.
Class of Evidence: NPub.org/coe
- Received March 1, 2021.
- Accepted in final form July 21, 2021.
- Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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