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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MDPI AG
2020-10-01
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| Online Access: | https://www.mdpi.com/2227-9059/8/10/410 |
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| author | Ana Cvetko Domagoj Kifer Olga Gornik Lucija Klarić Elizabeth Visser Gordan Lauc James F. Wilson Tamara Štambuk |
| author_facet | Ana Cvetko Domagoj Kifer Olga Gornik Lucija Klarić Elizabeth Visser Gordan Lauc James F. Wilson Tamara Štambuk |
| author_sort | Ana Cvetko |
| collection | DOAJ |
| description | 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 (<i>p</i> = 6.96 × 10<sup>−3</sup>) and abundance of high-mannose structures (<i>p</i> = 1.48 × 10<sup>−2</sup>) 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 (<i>p</i>-value range 1.66 × 10<sup>−2</sup>–4.28 × 10<sup>−2</sup>). 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. |
| first_indexed | 2024-03-10T15:41:47Z |
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| language | English |
| last_indexed | 2024-03-10T15:41:47Z |
| publishDate | 2020-10-01 |
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| series | Biomedicines |
| spelling | doaj.art-ca1af52a954f4ace8dc0b5a8713d49e62023-11-20T16:48:46ZengMDPI AGBiomedicines2227-90592020-10-0181041010.3390/biomedicines8100410Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory PotentialAna Cvetko0Domagoj Kifer1Olga Gornik2Lucija Klarić3Elizabeth Visser4Gordan Lauc5James F. Wilson6Tamara Štambuk7Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaFaculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaFaculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UKThe Institute of Applied Health Sciences, MRC University of Aberdeen, Aberdeen AB25 2ZD, UKFaculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UKFaculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaMultiple 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 (<i>p</i> = 6.96 × 10<sup>−3</sup>) and abundance of high-mannose structures (<i>p</i> = 1.48 × 10<sup>−2</sup>) 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 (<i>p</i>-value range 1.66 × 10<sup>−2</sup>–4.28 × 10<sup>−2</sup>). 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.https://www.mdpi.com/2227-9059/8/10/410immunoglobulin G in inflammationmultiple sclerosisN-glycosylationplasma glycoproteinsbiomarkers |
| spellingShingle | Ana Cvetko Domagoj Kifer Olga Gornik Lucija Klarić Elizabeth Visser Gordan Lauc James F. Wilson Tamara Štambuk Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential Biomedicines immunoglobulin G in inflammation multiple sclerosis N-glycosylation plasma glycoproteins biomarkers |
| title | Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential |
| title_full | Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential |
| title_fullStr | Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential |
| title_full_unstemmed | Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential |
| title_short | Glycosylation Alterations in Multiple Sclerosis Show Increased Proinflammatory Potential |
| title_sort | glycosylation alterations in multiple sclerosis show increased proinflammatory potential |
| topic | immunoglobulin G in inflammation multiple sclerosis N-glycosylation plasma glycoproteins biomarkers |
| url | https://www.mdpi.com/2227-9059/8/10/410 |
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