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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.01232

Intrathecal, not systemic inflammation is correlated with Multiple Sclerosis severity, especially in Progressive Multiple Sclerosis

  • 1National Institute of Allergy and Infectious Diseases (NIAID), United States

Objective
To test the hypothesis that Multiple Sclerosis (MS) patients have increased peripheral inflammation compared to healthy donors and that this systemic activation of the immune system, reflected by acute phase reactants (APRs) measured in the blood, contributes to intrathecal inflammation, which in turn contributes to the development of disability in MS.
Methods
Eight serum APRs measured in a prospectively-collected cross-sectional cohort with a total of 51 healthy donors and 291 untreated MS patients were standardized and assembled into related biomarker clusters to derive global measures of systemic inflammation. The resulting APR clusters were compared between diagnostic categories and correlated to equivalently-derived cerebrospinal fluid (CSF) biomarkers of innate and adaptive immunity. Finally, correlations were calculated between biomarkers of systemic and intrathecal inflammation and MS severity measures, which predict future rates of disability progression.
Results
While two blood APR clusters were elevated in MS patients, only one exhibited a weak correlation with MS severity. All CSF inflammation clusters, except CSF albumin, correlated with at least one measure of MS severity, with biomarkers of humoral adaptive immunity exhibiting the strongest correlations, especially in Progressive MS.
Conclusion
Systemic inflammation does not appear to be strongly associated with intrathecal inflammation in MS. Positive correlations between markers of intrathecal inflammation, especially of humoral immunity, with MS severity measures support a pathogenic role of intrathecal (compartmentalized) inflammation in central nervous system tissue destruction, including in Progressive MS.

Keywords: Multiple Sclerosis, Inflammation, Systemic infections, Cerebrospinal Fluid, Adaptive Immunity, T cells, Acute phase reactant, Progressive multiple sclerosis, B cells, innate immunity

Received: 09 Aug 2019; Accepted: 05 Nov 2019.

Copyright: © 2019 Milstein, Barbour, Jackson, Kosa and Bielekova. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Bibiana Bielekova, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD 20892-9807, Maryland, United States, Bibi.Bielekova@nih.gov