Abstract

BACKGROUND: The pathophysiology of multiple sclerosis disease progression remains undetermined. The aim of this study was to identify differences in plasma proteome during different stages of MS disease progression. METHODS: We used a multiplex aptamer proteomics platform (Somalogic) for sensitive detection of 1129 proteins in plasma. MS patients were selected and categorized based on baseline and a 4-year follow-up EDSS (delta EDSS) scores; relapse-onset (RO) slow progression (n = 31), RO with rapid progression (n = 29), primary progressive (n = 30), and healthy controls (n = 20). The relation of baseline plasma protein levels with delta EDSS and different MRI progression parameters were assessed using linear regression models. RESULTS: Regression analyses of plasma proteins with delta EDSS showed six significant associations. Strong associations were found for the proteins LGLAS8 (P = 7.64 × 10-5 , q = 0.06), CCL3 (P = 0.0001, q = 0.06), and RGMA (P = 0.0005, q = 0.09). In addition, associations of plasma proteins were found with percentage brain volume for C3 (P = 2,08 × 10-9 , q = 1,70 × 10-6 ), FGF9 (P = 3,42 × 10-9 , q = 1,70 × 10-6 ), and EHMT2 (P = 0.0007, q = 0.01). Most of the significant markers were associated with cell-cell and cell-extracellular matrix adhesion, immune system communication, immune system activation, and complement pathways. CONCLUSIONS: Our results revealed eight novel biomarkers related to clinical and radiological progression in MS. These results indicate that changes in immune system, complement pathway and ECM remodeling proteins contribute to MS progression and may therefore be further explored for use in prognosis of MS.
Original languageEnglish
Pages (from-to)1582-1594
Number of pages13
JournalAnnals of Clinical and Translational Neurology
Volume6
Issue number9
Early online date31 Jul 2019
DOIs
Publication statusPublished - 1 Sep 2019

Cite this

@article{ef2019c4105c490293dbf681a7d0dced,
title = "Plasma proteome in multiple sclerosis disease progression",
abstract = "BACKGROUND: The pathophysiology of multiple sclerosis disease progression remains undetermined. The aim of this study was to identify differences in plasma proteome during different stages of MS disease progression. METHODS: We used a multiplex aptamer proteomics platform (Somalogic) for sensitive detection of 1129 proteins in plasma. MS patients were selected and categorized based on baseline and a 4-year follow-up EDSS (delta EDSS) scores; relapse-onset (RO) slow progression (n = 31), RO with rapid progression (n = 29), primary progressive (n = 30), and healthy controls (n = 20). The relation of baseline plasma protein levels with delta EDSS and different MRI progression parameters were assessed using linear regression models. RESULTS: Regression analyses of plasma proteins with delta EDSS showed six significant associations. Strong associations were found for the proteins LGLAS8 (P = 7.64 × 10-5 , q = 0.06), CCL3 (P = 0.0001, q = 0.06), and RGMA (P = 0.0005, q = 0.09). In addition, associations of plasma proteins were found with percentage brain volume for C3 (P = 2,08 × 10-9 , q = 1,70 × 10-6 ), FGF9 (P = 3,42 × 10-9 , q = 1,70 × 10-6 ), and EHMT2 (P = 0.0007, q = 0.01). Most of the significant markers were associated with cell-cell and cell-extracellular matrix adhesion, immune system communication, immune system activation, and complement pathways. CONCLUSIONS: Our results revealed eight novel biomarkers related to clinical and radiological progression in MS. These results indicate that changes in immune system, complement pathway and ECM remodeling proteins contribute to MS progression and may therefore be further explored for use in prognosis of MS.",
author = "Arjan Malekzadeh and Cyra Leurs and {van Wieringen}, Wessel and Steenwijk, {Martijn D.} and Schoonheim, {Menno M.} and Michael Amann and Yvonne Naegelin and Jens Kuhle and Joep Killestein and Teunissen, {Charlotte E.}",
note = "{\circledC} 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.",
year = "2019",
month = "9",
day = "1",
doi = "10.1002/acn3.771",
language = "English",
volume = "6",
pages = "1582--1594",
journal = "Annals of Clinical and Translational Neurology",
issn = "2328-9503",
publisher = "John Wiley and Sons Ltd",
number = "9",

}

Plasma proteome in multiple sclerosis disease progression. / Malekzadeh, Arjan; Leurs, Cyra; van Wieringen, Wessel; Steenwijk, Martijn D.; Schoonheim, Menno M.; Amann, Michael; Naegelin, Yvonne; Kuhle, Jens; Killestein, Joep; Teunissen, Charlotte E.

In: Annals of Clinical and Translational Neurology, Vol. 6, No. 9, 01.09.2019, p. 1582-1594.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Plasma proteome in multiple sclerosis disease progression

AU - Malekzadeh, Arjan

AU - Leurs, Cyra

AU - van Wieringen, Wessel

AU - Steenwijk, Martijn D.

AU - Schoonheim, Menno M.

AU - Amann, Michael

AU - Naegelin, Yvonne

AU - Kuhle, Jens

AU - Killestein, Joep

AU - Teunissen, Charlotte E.

N1 - © 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - BACKGROUND: The pathophysiology of multiple sclerosis disease progression remains undetermined. The aim of this study was to identify differences in plasma proteome during different stages of MS disease progression. METHODS: We used a multiplex aptamer proteomics platform (Somalogic) for sensitive detection of 1129 proteins in plasma. MS patients were selected and categorized based on baseline and a 4-year follow-up EDSS (delta EDSS) scores; relapse-onset (RO) slow progression (n = 31), RO with rapid progression (n = 29), primary progressive (n = 30), and healthy controls (n = 20). The relation of baseline plasma protein levels with delta EDSS and different MRI progression parameters were assessed using linear regression models. RESULTS: Regression analyses of plasma proteins with delta EDSS showed six significant associations. Strong associations were found for the proteins LGLAS8 (P = 7.64 × 10-5 , q = 0.06), CCL3 (P = 0.0001, q = 0.06), and RGMA (P = 0.0005, q = 0.09). In addition, associations of plasma proteins were found with percentage brain volume for C3 (P = 2,08 × 10-9 , q = 1,70 × 10-6 ), FGF9 (P = 3,42 × 10-9 , q = 1,70 × 10-6 ), and EHMT2 (P = 0.0007, q = 0.01). Most of the significant markers were associated with cell-cell and cell-extracellular matrix adhesion, immune system communication, immune system activation, and complement pathways. CONCLUSIONS: Our results revealed eight novel biomarkers related to clinical and radiological progression in MS. These results indicate that changes in immune system, complement pathway and ECM remodeling proteins contribute to MS progression and may therefore be further explored for use in prognosis of MS.

AB - BACKGROUND: The pathophysiology of multiple sclerosis disease progression remains undetermined. The aim of this study was to identify differences in plasma proteome during different stages of MS disease progression. METHODS: We used a multiplex aptamer proteomics platform (Somalogic) for sensitive detection of 1129 proteins in plasma. MS patients were selected and categorized based on baseline and a 4-year follow-up EDSS (delta EDSS) scores; relapse-onset (RO) slow progression (n = 31), RO with rapid progression (n = 29), primary progressive (n = 30), and healthy controls (n = 20). The relation of baseline plasma protein levels with delta EDSS and different MRI progression parameters were assessed using linear regression models. RESULTS: Regression analyses of plasma proteins with delta EDSS showed six significant associations. Strong associations were found for the proteins LGLAS8 (P = 7.64 × 10-5 , q = 0.06), CCL3 (P = 0.0001, q = 0.06), and RGMA (P = 0.0005, q = 0.09). In addition, associations of plasma proteins were found with percentage brain volume for C3 (P = 2,08 × 10-9 , q = 1,70 × 10-6 ), FGF9 (P = 3,42 × 10-9 , q = 1,70 × 10-6 ), and EHMT2 (P = 0.0007, q = 0.01). Most of the significant markers were associated with cell-cell and cell-extracellular matrix adhesion, immune system communication, immune system activation, and complement pathways. CONCLUSIONS: Our results revealed eight novel biomarkers related to clinical and radiological progression in MS. These results indicate that changes in immune system, complement pathway and ECM remodeling proteins contribute to MS progression and may therefore be further explored for use in prognosis of MS.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31364818

U2 - 10.1002/acn3.771

DO - 10.1002/acn3.771

M3 - Article

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JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

SN - 2328-9503

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