Inflammation-related plasma and CSF biomarkers for multiple sclerosis

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Inflammation-related plasma and CSF biomarkers for multiple sclerosis. / Huang, Jesse; Khademi, Mohsen; Fugger, Lars; Lindhe, Örjan; Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Constantinescu, Clara; Lycke, Jan; Piehl, Fredrik; Olsson, Tomas; Kockum, Ingrid.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 117, No. 23, 09.06.2020, p. 12952-12960.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Huang, J, Khademi, M, Fugger, L, Lindhe, Ö, Novakova, L, Axelsson, M, Malmeström, C, Constantinescu, C, Lycke, J, Piehl, F, Olsson, T & Kockum, I 2020, 'Inflammation-related plasma and CSF biomarkers for multiple sclerosis', Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 23, pp. 12952-12960. https://doi.org/10.1073/pnas.1912839117

APA

Huang, J., Khademi, M., Fugger, L., Lindhe, Ö., Novakova, L., Axelsson, M., Malmeström, C., Constantinescu, C., Lycke, J., Piehl, F., Olsson, T., & Kockum, I. (2020). Inflammation-related plasma and CSF biomarkers for multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America, 117(23), 12952-12960. https://doi.org/10.1073/pnas.1912839117

CBE

Huang J, Khademi M, Fugger L, Lindhe Ö, Novakova L, Axelsson M, Malmeström C, Constantinescu C, Lycke J, Piehl F, Olsson T, Kockum I. 2020. Inflammation-related plasma and CSF biomarkers for multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America. 117(23):12952-12960. https://doi.org/10.1073/pnas.1912839117

MLA

Huang, Jesse et al. "Inflammation-related plasma and CSF biomarkers for multiple sclerosis". Proceedings of the National Academy of Sciences of the United States of America. 2020, 117(23). 12952-12960. https://doi.org/10.1073/pnas.1912839117

Vancouver

Huang J, Khademi M, Fugger L, Lindhe Ö, Novakova L, Axelsson M et al. Inflammation-related plasma and CSF biomarkers for multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America. 2020 Jun 9;117(23):12952-12960. https://doi.org/10.1073/pnas.1912839117

Author

Huang, Jesse ; Khademi, Mohsen ; Fugger, Lars ; Lindhe, Örjan ; Novakova, Lenka ; Axelsson, Markus ; Malmeström, Clas ; Constantinescu, Clara ; Lycke, Jan ; Piehl, Fredrik ; Olsson, Tomas ; Kockum, Ingrid. / Inflammation-related plasma and CSF biomarkers for multiple sclerosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2020 ; Vol. 117, No. 23. pp. 12952-12960.

Bibtex

@article{207db4eb959246f285d4adff2992e21b,
title = "Inflammation-related plasma and CSF biomarkers for multiple sclerosis",
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. ",
keywords = "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",
author = "Jesse Huang and Mohsen Khademi and Lars Fugger and {\"O}rjan Lindhe and Lenka Novakova and Markus Axelsson and Clas Malmestr{\"o}m and Clara Constantinescu and Jan Lycke and Fredrik Piehl and Tomas Olsson and Ingrid Kockum",
note = "Copyright {\textcopyright} 2020 the Author(s). Published by PNAS.",
year = "2020",
month = jun,
day = "9",
doi = "10.1073/pnas.1912839117",
language = "English",
volume = "117",
pages = "12952--12960",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "23",

}

RIS

TY - JOUR

T1 - Inflammation-related plasma and CSF biomarkers for multiple sclerosis

AU - Huang, Jesse

AU - Khademi, Mohsen

AU - Fugger, Lars

AU - Lindhe, Örjan

AU - Novakova, Lenka

AU - Axelsson, Markus

AU - Malmeström, Clas

AU - Constantinescu, Clara

AU - Lycke, Jan

AU - Piehl, Fredrik

AU - Olsson, Tomas

AU - Kockum, Ingrid

N1 - Copyright © 2020 the Author(s). Published by PNAS.

PY - 2020/6/9

Y1 - 2020/6/9

N2 - 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.

AB - 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.

KW - Adult

KW - Biomarkers/blood

KW - Case-Control Studies

KW - Chemokine CCL11/analysis

KW - Chemokine CCL20/blood

KW - Cohort Studies

KW - Female

KW - Humans

KW - Inflammation/blood

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis/blood

KW - Prognosis

KW - Proteomics

KW - Reproducibility of Results

KW - Severity of Illness Index

KW - Young Adult

KW - Multiple sclerosis

KW - Cerebrospinal fluid

KW - Biomarkers

KW - Proximity extension assay

KW - CHEMOKINES

KW - CEREBROSPINAL-FLUID

KW - extension assay

KW - NEUROFILAMENT

KW - MULTIPLE-SCLEROSIS

KW - DISABILITY

KW - T-CELLS

KW - BLOOD

KW - proteomics

KW - biomarkers

KW - multiple sclerosis

KW - NATALIZUMAB

KW - proximity

KW - cerebrospinal fluid

KW - PLACEBO-CONTROLLED TRIAL

KW - EXPRESSION

U2 - 10.1073/pnas.1912839117

DO - 10.1073/pnas.1912839117

M3 - Journal article

C2 - 32457139

VL - 117

SP - 12952

EP - 12960

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 23

ER -