Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential

Cvetko, Ana; Kifer, Domagoj; Gornik, Olga; Klarić, Lucija; Visser, Elizabeth; Lauc, Gordan; Wilson, James F.; Štambuk, Tamara

doi:10.3390/biomedicines8100410

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Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential

¹,

^1,2

⁴,

^1,2,*,

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^1,2,*

Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia

Genos Glycoscience Research Laboratory, 10000 Zagreb, Croatia

MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK

⁴

The Institute of Applied Health Sciences, MRC University of Aberdeen, Aberdeen AB25 2ZD, UK

⁵

Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh EH8 9AG, UK

Authors to whom correspondence should be addressed.

Biomedicines 2020, 8(10), 410; https://doi.org/10.3390/biomedicines8100410

Received: 27 August 2020 / Revised: 2 October 2020 / Accepted: 10 October 2020 / Published: 13 October 2020

(This article belongs to the Special Issue Immunoglobulins in Inflammation)

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Abstract

Multiple sclerosis (MS) is an inflammatory autoimmune disorder affecting the central nervous system (CNS), with unresolved aetiology. Previous studies have implicated N-glycosylation, a highly regulated enzymatic attachment of complex sugars to targeted proteins, in MS pathogenesis. We investigated individual variation in N-glycosylation of the total plasma proteome and of IgG in MS. Both plasma protein and IgG N-glycans were chromatographically profiled and quantified in 83 MS cases and 88 age- and sex-matched controls. Comparing levels of glycosylation features between MS cases and controls revealed that core fucosylation (p = 6.96 × 10⁻³) and abundance of high-mannose structures (p = 1.48 × 10⁻²) were the most prominently altered IgG glycosylation traits. Significant changes in plasma protein N-glycome composition were observed for antennary fucosylated, tri- and tetrasialylated, tri- and tetragalactosylated, high-branched N-glycans (p-value range 1.66 × 10⁻²–4.28 × 10⁻²). Classification performance of N-glycans was examined by ROC curve analysis, resulting in an AUC of 0.852 for the total plasma N-glycome and 0.798 for IgG N-glycome prediction models. Our results indicate that multiple aspects of protein glycosylation are altered in MS, showing increased proinflammatory potential. N-glycan alterations showed substantial value in classification of the disease status, nonetheless, additional studies are warranted to explore their exact role in MS development and utility as biomarkers. View Full-Text

Keywords: immunoglobulin G in inflammation; multiple sclerosis; N-glycosylation; plasma glycoproteins; biomarkers

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MDPI and ACS Style

Cvetko, A.; Kifer, D.; Gornik, O.; Klarić, L.; Visser, E.; Lauc, G.; Wilson, J.F.; Štambuk, T. Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential. Biomedicines 2020, 8, 410. https://doi.org/10.3390/biomedicines8100410

AMA Style

Cvetko A, Kifer D, Gornik O, Klarić L, Visser E, Lauc G, Wilson JF, Štambuk T. Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential. Biomedicines. 2020; 8(10):410. https://doi.org/10.3390/biomedicines8100410

Chicago/Turabian Style

Cvetko, Ana, Domagoj Kifer, Olga Gornik, Lucija Klarić, Elizabeth Visser, Gordan Lauc, James F. Wilson, and Tamara Štambuk. 2020. "Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential" Biomedicines 8, no. 10: 410. https://doi.org/10.3390/biomedicines8100410

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Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential

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