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 sens...

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Main Authors: Arjan Malekzadeh, Cyra Leurs, Wessel vanWieringen, Martijn D. Steenwijk, Menno M. Schoonheim, Michael Amann, Yvonne Naegelin, Jens Kuhle, Joep Killestein, Charlotte E. Teunissen
Format: Article
Language:English
Published: Wiley 2019-09-01
Series:Annals of Clinical and Translational Neurology
Online Access:https://doi.org/10.1002/acn3.771
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author Arjan Malekzadeh
Cyra Leurs
Wessel vanWieringen
Martijn D. Steenwijk
Menno M. Schoonheim
Michael Amann
Yvonne Naegelin
Jens Kuhle
Joep Killestein
Charlotte E. Teunissen
author_facet Arjan Malekzadeh
Cyra Leurs
Wessel vanWieringen
Martijn D. Steenwijk
Menno M. Schoonheim
Michael Amann
Yvonne Naegelin
Jens Kuhle
Joep Killestein
Charlotte E. Teunissen
author_sort Arjan Malekzadeh
collection DOAJ
description 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.
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spelling doaj.art-2dcba6eb08e94bdeb938fb2fc1264d0b2022-12-21T18:56:07ZengWileyAnnals of Clinical and Translational Neurology2328-95032019-09-01691582159410.1002/acn3.771Plasma proteome in multiple sclerosis disease progressionArjan Malekzadeh0Cyra Leurs1Wessel vanWieringen2Martijn D. Steenwijk3Menno M. Schoonheim4Michael Amann5Yvonne Naegelin6Jens Kuhle7Joep Killestein8Charlotte E. Teunissen9Department of Clinical Chemistry Amsterdam University Medical Centre Amsterdam The NetherlandsDepartment of Neurology Amsterdam University Medical Centre Amsterdam The NetherlandsDepartment of Mathematics Amsterdam University Medical Centre Amsterdam The NetherlandsDepartment of Anatomy and Neurosciences Amsterdam Neuroscience MS Center Amsterdam Amsterdam University Medical Centre Amsterdam The NetherlandsDepartment of Anatomy and Neurosciences Amsterdam Neuroscience MS Center Amsterdam Amsterdam University Medical Centre Amsterdam The NetherlandsDivision of Diagnostic and Interventional Neuroradiology Department of Radiology and Nuclear Medicine University Hospital Basel Basel SwitzerlandDepartment of Biomedicine and Clinical Research University Hospital Basel Basel SwitzerlandDepartment of Biomedicine and Clinical Research University Hospital Basel Basel SwitzerlandDepartment of Neurology Amsterdam University Medical Centre Amsterdam The NetherlandsDepartment of Clinical Chemistry Amsterdam University Medical Centre Amsterdam The NetherlandsAbstract 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.https://doi.org/10.1002/acn3.771
spellingShingle Arjan Malekzadeh
Cyra Leurs
Wessel vanWieringen
Martijn D. Steenwijk
Menno M. Schoonheim
Michael Amann
Yvonne Naegelin
Jens Kuhle
Joep Killestein
Charlotte E. Teunissen
Plasma proteome in multiple sclerosis disease progression
Annals of Clinical and Translational Neurology
title Plasma proteome in multiple sclerosis disease progression
title_full Plasma proteome in multiple sclerosis disease progression
title_fullStr Plasma proteome in multiple sclerosis disease progression
title_full_unstemmed Plasma proteome in multiple sclerosis disease progression
title_short Plasma proteome in multiple sclerosis disease progression
title_sort plasma proteome in multiple sclerosis disease progression
url https://doi.org/10.1002/acn3.771
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