CSF inflammatory biomarkers responsive to treatment in progressive multiple sclerosis capture residual inflammation associated with axonal damage

Multiple Sclerosis : Clinical and Laboratory Research
Jeppe Romme ChristensenFinn Sellebjerg

Abstract

Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation. To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers. CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS. CSF concentrations of 20 inflammatory biomarkers and CSF biomarkers of axonal damage (neurofilament light chain (NFL)) and demyelination were analysed using electrochemiluminescent assay and enzyme-linked immunosorbent assay (ELISA). In all, 17 natalizumab- and 23 methylprednisolone-treated patients had paired CSF samples. CSF sCD27 displayed superior standardised response means and highly significant decreases during both natalizumab and methylprednisolone treatment; however, post-treatment levels remained above healthy donor reference levels. Correlation analyses of CSF inflammatory biomarkers and NFL before, during and after treatment demonstrated that CSF sCD27 consistently correlates with NFL. ...Continue Reading

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Citations

Apr 4, 2019·Nature Reviews. Neurology·Dalia Rotstein, Xavier Montalban
Apr 30, 2019·Frontiers in Immunology·Florian DeisenhammerUwe K Zettl
May 25, 2020·Journal of Neurology·Thomas WilliamsJeremy Chataway
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Apr 24, 2021·Frontiers in Neuroscience·Carolina Ferreira-AtuestaSharmilee Gnanapavan
May 14, 2021·Multiple Sclerosis and Related Disorders·Alexander Cuculiza HenriksenJeppe Romme Christensen
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Aug 26, 2021·Neurology. Neuroimmunology and Neuroinflammation·Helene Højsgaard ChowFinn Sellebjerg

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA

Clinical Trials Mentioned

NCT01077466
NCT01305837

Software Mentioned

SPSS

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