Detection of Glycan Shedding in the Blood: New Class of Multiple Sclerosis Biomarkers?

Research output: Contribution to journalJournal article – Annual report year: 2018Researchpeer-review

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Detection of Glycan Shedding in the Blood: New Class of Multiple Sclerosis Biomarkers? / DellaValle, Brian; Manresa-Arraut, Alba; Hasseldam, Henrik; Stensballe, Allan; Rungby, Jørgen; Larsen, Agnete; Hempel, Casper.

In: Frontiers in Immunology, Vol. 9, 1254, 2018.

Research output: Contribution to journalJournal article – Annual report year: 2018Researchpeer-review

Harvard

DellaValle, B, Manresa-Arraut, A, Hasseldam, H, Stensballe, A, Rungby, J, Larsen, A & Hempel, C 2018, 'Detection of Glycan Shedding in the Blood: New Class of Multiple Sclerosis Biomarkers?', Frontiers in Immunology, vol. 9, 1254. https://doi.org/10.3389/fimmu.2018.01254

APA

DellaValle, B., Manresa-Arraut, A., Hasseldam, H., Stensballe, A., Rungby, J., Larsen, A., & Hempel, C. (2018). Detection of Glycan Shedding in the Blood: New Class of Multiple Sclerosis Biomarkers? Frontiers in Immunology, 9, [1254]. https://doi.org/10.3389/fimmu.2018.01254

CBE

MLA

Vancouver

DellaValle B, Manresa-Arraut A, Hasseldam H, Stensballe A, Rungby J, Larsen A et al. Detection of Glycan Shedding in the Blood: New Class of Multiple Sclerosis Biomarkers? Frontiers in Immunology. 2018;9. 1254. https://doi.org/10.3389/fimmu.2018.01254

Author

DellaValle, Brian ; Manresa-Arraut, Alba ; Hasseldam, Henrik ; Stensballe, Allan ; Rungby, Jørgen ; Larsen, Agnete ; Hempel, Casper. / Detection of Glycan Shedding in the Blood: New Class of Multiple Sclerosis Biomarkers?. In: Frontiers in Immunology. 2018 ; Vol. 9.

Bibtex

@article{3e45006a3af1413b825ef50066b8b941,
title = "Detection of Glycan Shedding in the Blood: New Class of Multiple Sclerosis Biomarkers?",
abstract = "Introduction: Multiple sclerosis (MS) is a devastating autoimmune disease, afflicting people in the prime of their lives. Presently, after initial clinical presentation, there are no reliable markers for whether a patient will develop MS, or whether their prognosis will be aggressive or relapsing-remitting. Furthermore, many MS patients do not respond to treatment. Thus, markers for diagnosis, prognosis, and treatment-responsiveness are lacking for a disease, where a precision medicine approach would be valuable. The glycocalyx (GLX) is the carbohydrate-rich outer surface of the blood vessel wall and is the first interaction between the blood and the vessel. We hypothesized that cleavage of the GLX may be an early stage predictor of immune attack, blood-brain barrier (BBB) breakdown, and disease severity in MS.Methods: Two experimental models of MS, experimental autoimmune encephalitis (EAE), were included in this study. EAE was induced in C57BL/6J mice and Lewis rats, which were monitored for weight loss and clinical presentation in comparison to healthy controls. Plasma samples were obtained longitudinally from mice until peak disease severity and at peak disease severity in rats. Soluble GLX-associated glycosaminoglycans (GAG) and proteoglycans (PG) were detected in plasma samples.Results: All animals receiving EAE emulsion developed fulminant EAE (100{\%} penetrance). Increased plasma levels of chondroitin sulfate were detected before the onset of clinical symptoms and remained elevated at peak disease severity. Hyaluronic acid was increased at the height of the disease, whereas heparan sulfate was transiently increased during early stages only. By contrast, syndecans 1, 3, and 4 were detected in EAE samples as well as healthy controls, with no significant differences between the two groups.Discussion: In this study, we present data supporting the shedding of the GLX as a new class of biomarker for MS. In particular, soluble, sugar-based GLX components are associated with disease severity in two models of MS, molecules that would not be detected in proteomics-based screens of MS patient samples. Patient studies are presently underway.",
keywords = "Glycocalyx, Multiple sclerosis, Precision medicine, Biomarkers, Glycosaminoglycans, Proteoglycans, EAE, BBB",
author = "Brian DellaValle and Alba Manresa-Arraut and Henrik Hasseldam and Allan Stensballe and J{\o}rgen Rungby and Agnete Larsen and Casper Hempel",
year = "2018",
doi = "10.3389/fimmu.2018.01254",
language = "English",
volume = "9",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - Detection of Glycan Shedding in the Blood: New Class of Multiple Sclerosis Biomarkers?

AU - DellaValle, Brian

AU - Manresa-Arraut, Alba

AU - Hasseldam, Henrik

AU - Stensballe, Allan

AU - Rungby, Jørgen

AU - Larsen, Agnete

AU - Hempel, Casper

PY - 2018

Y1 - 2018

N2 - Introduction: Multiple sclerosis (MS) is a devastating autoimmune disease, afflicting people in the prime of their lives. Presently, after initial clinical presentation, there are no reliable markers for whether a patient will develop MS, or whether their prognosis will be aggressive or relapsing-remitting. Furthermore, many MS patients do not respond to treatment. Thus, markers for diagnosis, prognosis, and treatment-responsiveness are lacking for a disease, where a precision medicine approach would be valuable. The glycocalyx (GLX) is the carbohydrate-rich outer surface of the blood vessel wall and is the first interaction between the blood and the vessel. We hypothesized that cleavage of the GLX may be an early stage predictor of immune attack, blood-brain barrier (BBB) breakdown, and disease severity in MS.Methods: Two experimental models of MS, experimental autoimmune encephalitis (EAE), were included in this study. EAE was induced in C57BL/6J mice and Lewis rats, which were monitored for weight loss and clinical presentation in comparison to healthy controls. Plasma samples were obtained longitudinally from mice until peak disease severity and at peak disease severity in rats. Soluble GLX-associated glycosaminoglycans (GAG) and proteoglycans (PG) were detected in plasma samples.Results: All animals receiving EAE emulsion developed fulminant EAE (100% penetrance). Increased plasma levels of chondroitin sulfate were detected before the onset of clinical symptoms and remained elevated at peak disease severity. Hyaluronic acid was increased at the height of the disease, whereas heparan sulfate was transiently increased during early stages only. By contrast, syndecans 1, 3, and 4 were detected in EAE samples as well as healthy controls, with no significant differences between the two groups.Discussion: In this study, we present data supporting the shedding of the GLX as a new class of biomarker for MS. In particular, soluble, sugar-based GLX components are associated with disease severity in two models of MS, molecules that would not be detected in proteomics-based screens of MS patient samples. Patient studies are presently underway.

AB - Introduction: Multiple sclerosis (MS) is a devastating autoimmune disease, afflicting people in the prime of their lives. Presently, after initial clinical presentation, there are no reliable markers for whether a patient will develop MS, or whether their prognosis will be aggressive or relapsing-remitting. Furthermore, many MS patients do not respond to treatment. Thus, markers for diagnosis, prognosis, and treatment-responsiveness are lacking for a disease, where a precision medicine approach would be valuable. The glycocalyx (GLX) is the carbohydrate-rich outer surface of the blood vessel wall and is the first interaction between the blood and the vessel. We hypothesized that cleavage of the GLX may be an early stage predictor of immune attack, blood-brain barrier (BBB) breakdown, and disease severity in MS.Methods: Two experimental models of MS, experimental autoimmune encephalitis (EAE), were included in this study. EAE was induced in C57BL/6J mice and Lewis rats, which were monitored for weight loss and clinical presentation in comparison to healthy controls. Plasma samples were obtained longitudinally from mice until peak disease severity and at peak disease severity in rats. Soluble GLX-associated glycosaminoglycans (GAG) and proteoglycans (PG) were detected in plasma samples.Results: All animals receiving EAE emulsion developed fulminant EAE (100% penetrance). Increased plasma levels of chondroitin sulfate were detected before the onset of clinical symptoms and remained elevated at peak disease severity. Hyaluronic acid was increased at the height of the disease, whereas heparan sulfate was transiently increased during early stages only. By contrast, syndecans 1, 3, and 4 were detected in EAE samples as well as healthy controls, with no significant differences between the two groups.Discussion: In this study, we present data supporting the shedding of the GLX as a new class of biomarker for MS. In particular, soluble, sugar-based GLX components are associated with disease severity in two models of MS, molecules that would not be detected in proteomics-based screens of MS patient samples. Patient studies are presently underway.

KW - Glycocalyx

KW - Multiple sclerosis

KW - Precision medicine

KW - Biomarkers

KW - Glycosaminoglycans

KW - Proteoglycans

KW - EAE

KW - BBB

U2 - 10.3389/fimmu.2018.01254

DO - 10.3389/fimmu.2018.01254

M3 - Journal article

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 1254

ER -