期刊
BIOMEDICINES
卷 8, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines8100410
关键词
immunoglobulin G in inflammation; multiple sclerosis; N-glycosylation; plasma glycoproteins; biomarkers
资金
- MS Society UK
- Volant Trust
- Royal Society
- European Structural and Investments funding [KK.01.1.1.01.0010, KK.01.2.2.03.0006]
- Innovative Medicines Initiative 2 Joint Undertaking (JU) (3TR) [831434]
- European Union's Horizon 2020 research and innovation programme
- EFPIA
- RCUK Innovation Fellowship from the National Productivity Investment Fund [MR/R026408/1]
- MRC [MR/R026408/1] Funding Source: UKRI
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 x 10(-3)) and abundance of high-mannose structures (p = 1.48 x 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 x 10(-2)-4.28 x 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.
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