Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential

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...

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Veröffentlicht in:Biomedicines 2020-10, Vol.8 (10), p.410
Hauptverfasser: Cvetko, Ana, Kifer, Domagoj, Gornik, Olga, Klarić, Lucija, Visser, Elizabeth, Lauc, Gordan, Wilson, James F, Štambuk, Tamara
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Sprache:eng
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Zusammenfassung: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 ( = 6.96 × 10 ) and abundance of high-mannose structures ( = 1.48 × 10 ) 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 ( -value range 1.66 × 10 -4.28 × 10 ). 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.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines8100410