Inflammation-related plasma and CSF biomarkers for multiple sclerosis

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DOI

  • Jesse Huang, Karolinska Univ Hosp, Karolinska Institutet, Karolinska University Hospital
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  • Mohsen Khademi, Karolinska Univ Hosp, Karolinska Institutet, Karolinska University Hospital
  • ,
  • Lars Fugger
  • Örjan Lindhe, Uppsala University, Uppsala, Sweden, Jonkobing, Sweden
  • ,
  • Lenka Novakova, Univ Gothenburg, University of Gothenburg, Gothenburg Global Biodivers Ctr
  • ,
  • Markus Axelsson, Univ Gothenburg, University of Gothenburg, Gothenburg Global Biodivers Ctr
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  • Clas Malmeström, Univ Gothenburg, University of Gothenburg, Gothenburg Global Biodivers Ctr
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  • Clara Constantinescu, Univ Gothenburg, University of Gothenburg, Gothenburg Global Biodivers Ctr
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  • Jan Lycke, Univ Gothenburg, University of Gothenburg, Gothenburg Global Biodivers Ctr
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  • Fredrik Piehl, Karolinska Univ Hosp, Karolinska Institutet, Karolinska University Hospital
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  • Tomas Olsson, Karolinska Univ Hosp, Karolinska Institutet, Karolinska University Hospital
  • ,
  • Ingrid Kockum, Karolinska Univ Hosp, Karolinska Institutet, Karolinska University Hospital

Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (P CSF < 4 × 10 −5, P plasma < 4 × 10 −5), and plasma CCL20 was associated with disease severity (P = 4 × 10 −5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue23
Pages (from-to)12952-12960
Number of pages9
ISSN0027-8424
DOIs
Publication statusPublished - 9 Jun 2020
Externally publishedYes

    Research areas

  • Adult, Biomarkers/blood, Case-Control Studies, Chemokine CCL11/analysis, Chemokine CCL20/blood, Cohort Studies, Female, Humans, Inflammation/blood, Male, Middle Aged, Multiple Sclerosis/blood, Prognosis, Proteomics, Reproducibility of Results, Severity of Illness Index, Young Adult, Multiple sclerosis, Cerebrospinal fluid, Biomarkers, Proximity extension assay, CHEMOKINES, CEREBROSPINAL-FLUID, extension assay, NEUROFILAMENT, MULTIPLE-SCLEROSIS, DISABILITY, T-CELLS, BLOOD, proteomics, biomarkers, multiple sclerosis, NATALIZUMAB, proximity, cerebrospinal fluid, PLACEBO-CONTROLLED TRIAL, EXPRESSION

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