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Cited by 194Multiple Sclerosis Research StudiesPeripheral Neuropathies and DisordersPsoriasis: Treatment and Pathogenesis

Inflammation-related plasma and CSF biomarkers for multiple sclerosis

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Huang, Jesse, Khademi, Mohsen, Fugger, Lars, Lindhe, Örjan, Novakova, Lenka, Axelsson, Markus, Malmeström, Clas, Constantinescu, Clara +4 more·2020·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1912839117PMC PMC7293699
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Abstract

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.

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  • OPCs have been suggested to express the primary CCL11 receptor CCR3, and elevated CCL11 levels are associated with MS disease duration and severity.

    “Moreover, OPCs have been suggested to express the primary CCL11 receptor, CCR360 and elevated CCL11 levels are associated with MS disease duration and severity61,62.”

    From Senescent-like microglia limit remyelination through the senescence associated secretory phenotype (2025) · cites this paper as [62]

    The Results section on clinical course reports that CCL11 increased with MS disease duration and showed a suggestive increase in secondary progressive versus relapsing–remitting disease. It does not report an association between CCL11 and measured disease severity; the Results and Discussion instead identify CCL20 as associated with severity. The separate CCR3 statement is attached to citation 60, not this source. (LLM, conf=0.90)

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Authors
Huang, J., Khademi, M., Fugger, L., Lindhe, Ö., Novakova, L., Axelsson, M., Malmeström, C., Constantinescu, C., Lycke, J., Piehl, F., Olsson, T., & Kockum, I.
Affiliations
  • Karolinska University Hospital (SE)
  • John Radcliffe Hospital (GB)
  • Olink Bioscience (Sweden) (SE)
  • University of Gothenburg (SE)
Corresponding author
Kockum, Ingrid
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2020-05-26
Volume
117
Issue
23
Pages
12952-12960
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1912839117
PMC
PMC7293699
OpenAlex
W3032082124
Cited by
194
References
6
Citations by year
2026: 26 · 2025: 32 · 2024: 36 · 2023: 37 · 2022: 28 · 2021: 28 · 2020: 7
FWCI
16.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Vetenskapsrådet (2015-02419)
  • Hjärnfonden (NA)
  • OLINK's Young Scientist Competition (NA)
  • MS Forsknings Fonden (NA)
  • Multiple Sclerosis Society of Canada (EGID:3045)
  • Swedish Federal Government (ALFGBG-722081)
  • Swedish Association of Persons with Neurological Disabilities (NA)
  • Research Foundation of the Multiple Sclerosis Society of Gothenburg (NA)
  • Edit Jacobson Foundation (NA)
  • EC | Horizon 2020 (733161)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
multiple sclerosis, biomarkers, cerebrospinal fluid protein, plasma proteins, inflammation, IL12B, CD5, macrophage inflammatory protein-1alpha, CXCL9, OSM, hepatocyte growth factor, eotaxin, CCL20, natalizumab, fingolimod, treatment response monitoring, early disease detection, disease severity, disease duration
MeSH terms
Adult, Female, Humans, Inflammation, Male, Middle Aged, Multiple Sclerosis, Prognosis, Severity of Illness Index, Reproducibility of Results, Cohort Studies, Biomarkers, Case-Control Studies, Proteomics, Chemokine CCL11, Chemokine CCL20, Young Adult

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