Serum proteomic analysis of a pre‐symptomatic multiple sclerosis cohort

Wallin, Mitchell T.; Oh, Unsong; Nyalwidhe, Julius O.; Semmes, John; Kislinger, Thomas; Coffman, Parisa; Jf, Kurtzke; Jacobson, Steven

doi:10.1111/ene.12534

Cited by 16 publications

(21 citation statements)

References 19 publications

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“…Complement activation is a well‐known feature in gray matter lesions, these lesions were surrounded by complement receptor‐positive microglia, and known to contribute to irreversible MS progression . Additionally, the presence of C3 together with other complement factors, and Fibronectin aggregates at lesions have been shown to prevent remyelination and shown to be differentially regulated in serum of presymptomatic and symptomatic MS patients . We observed a significant increase of C3 plasma levels related to increasing brain atrophy and increased FN1 plasma levels in RO‐all compared to healthy controls.…”

Section: Discussioncontrasting

confidence: 99%

“…Previous MS biomarker studies performed mostly LC‐MS blood proteomics . Moreover, few studies have focused on the different progression courses within MS, making comparison with earlier publications challenging . Nonetheless, some of our results coincide with earlier findings from candidate approach and pathology based studies, as we will discuss below.…”

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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Plasma proteome in multiple sclerosis disease progression

Malekzadeh¹,

Leurs

Wieringen³

et al. 2019

Ann Clin Transl Neurol

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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; relapseonset (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 9 10 À5 , 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 9 10 À9 , q = 1,70 9 10 À6 ), FGF9 (P = 3,42 9 10 À9 , q = 1,70 9 10 À6 ), 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. 1582

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 88%

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Plasma proteome in multiple sclerosis disease progression

Malekzadeh¹,

Leurs

Wieringen³

et al. 2019

Ann Clin Transl Neurol

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“…Moreover, a more careful examination of the regulated pathways could reveal new therapeutic targets. Interestingly, a recent study using presymptomatic and postsymptomatic sera demonstrated that some proteins were differentially regulated in presymptomatic multiple sclerosis samples compared with the control samples . These data suggest that there are abnormalities even before the onset of symptoms.…”

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confidence: 98%

How can proteomics elucidate the complexity of multiple sclerosis?

Farias

Santos

2015

Proteomics Clinical Apps

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Multiple sclerosis affects more than 2.5 million people worldwide. Although multiple sclerosis was described almost 150 years ago, there are many knowledge gaps regarding its etiology, diagnosis, prognosis, and pathogenesis. Multiple sclerosis is an inflammatory, demyelinating, neurodegenerative disease of the CNS. During the last several decades, experimental models of multiple sclerosis have contributed to our understanding of the inflammatory disease mechanisms and have aided drug testing and development. However, little is known about the neurodegenerative mechanisms that operate during the evolution of the disease. Currently, all therapeutic approaches are primarily based on the inflammatory aspect of the disease. During the last decade, proteomics has emerged as a promising tool for revealing molecular pathways as well as identifying and quantifying differentially expressed proteins. Therefore, proteomics may be used for the discovery of biomarkers, potential drug targets, and new regulatory mechanisms. To date, a considerable number of proteomics studies have been conducted on samples from experimental models and patients with multiple sclerosis. These data form a solid base for further careful analysis and validation.

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“…Multiple sclerosis (MS) is a field of neurology that has undergone tremendous advances within only the last 15 years . The advent of immunological therapies has transformed outcome for patients with relapsing−remitting disease, although the effect on chronic progressive disease is less certain.…”

mentioning

confidence: 99%