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. 2019 Sep;6(9):1582-1594.
doi: 10.1002/acn3.771. Epub 2019 Jul 31.

Plasma proteome in multiple sclerosis disease progression

Arjan Malekzadeh  1 , Cyra Leurs  2 , Wessel van Wieringen  3 , Martijn D Steenwijk  4 , Menno M Schoonheim  4 , Michael Amann  5   6 , Yvonne Naegelin  7 , Jens Kuhle  7 , Joep Killestein  2 , Charlotte E Teunissen  1
Affiliations

Plasma proteome in multiple sclerosis disease progression

Arjan Malekzadeh et al. Ann Clin Transl Neurol. 2019 Sep.

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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Conflict of interest statement

C. Teunissen has functioned in advisory boards of Fujirebio and Roche, received nonfinancial support in the form of research consumables from ADxNeurosciences and Euroimmun, performed contract research or received grants from Probiodrug, Janssen prevention center, Boehringer, Brainsonline, AxonNeurosciences, EIP farma, Roche.

Jens Kuhle served on scientific advisory boards for Novartis Pharmaceuticals, Merck, Biogen, Sanofi Genzyme, Roche, and Bayer; has received funding for travel and/or speaker honoraria from Biogen, Sanofi Genzyme, Novartis, Merck Serono, Roche, Teva, and the Swiss MS Society; and received research support from Bayer, Biogen, Merck, Sanofi Genzyma, Novartis, Roche, ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation (320030_160221).

Joep Killestein has accepted speaker and consultancy fees from Merck, Biogen, Teva, Genzyme, Roche, and Novartis. M.P.W. received speaker and consultancy fees from Biogen, Biologix, Celgene, IXICO, Merck, Novartis, Roche, and Sanofi Genzyme.

Figures

Figure 1
Figure 1
Scatter plots of several significant markers associated with delta EDSS. On the y‐axis corrected Log10 levels of significant markers are shown, and on the x‐axis delta EDSS.
Figure 2
Figure 2
Scatter plots of PIK3CA complex associated with delta T1 hypo‐intense and delta T2 hyper‐intense volume. On the y‐axis corrected Log10 levels of significant markers are shown, and on the x‐axis delta delta T1 hypo‐intense volume and delta T2 hyper‐intense volume.
Figure 3
Figure 3
Scatter plots of several significant markers associated with percentage brain volume change (PBVC). On the y‐axis corrected Log10 levels of significant markers are shown, and on the x‐axis PBVC values for 2 years.
Figure 4
Figure 4
Venn‐diagram of overlapping significant plasma proteins (P < 0.05) associated with delta EDSS, delta T1 hypo‐intense volume, delta T2 hyper‐intense volume, and percentage brain volume change (PBVC).
Figure 5
Figure 5
Graphical representation of several significant markers for different group comparisons. On the y‐axis corrected Log10 levels of significant markers are shown. The dark lines in the boxplot represent the median, and the whiskers represent the 95% confidence interval.
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