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Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet’s Disease
Behcet’s disease (BD) is an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death. Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no sig...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650305/ https://www.ncbi.nlm.nih.gov/pubmed/34888356 http://dx.doi.org/10.3389/fmolb.2021.778851 |
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author | Seo, Nari Lee, Hyunjun Oh, Myung Jin Kim, Ga Hyeon Lee, Sang Gil Ahn, Joong Kyong Cha, Hoon-Suk Kim, Kyoung Heon Kim, Jaehan An, Hyun Joo |
author_facet | Seo, Nari Lee, Hyunjun Oh, Myung Jin Kim, Ga Hyeon Lee, Sang Gil Ahn, Joong Kyong Cha, Hoon-Suk Kim, Kyoung Heon Kim, Jaehan An, Hyun Joo |
author_sort | Seo, Nari |
collection | PubMed |
description | Behcet’s disease (BD) is an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death. Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity. As the link between glycosylation and the immune system has been revealed, research on the immunological function of glycans is being actively conducted. In particular, sialic acids at the terminus of glycoconjugates are directly implicated in immune responses, cell–cell/pathogen interactions, and tumor progression. Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases. Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans. Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex(5)HexNAc(4)NeuAc(1), Hex(5)HexNAc(4)Fuc(1)NeuAc(1), and Hex(5)HexNAc(4)NeuAc(2). Among them, three isomers almost completely distinguished BD from control with high sensitivity and specificity with an area under the curve (AUC) of 0.945, suggesting the potential as novel BD biomarkers. In particular, it was confirmed that α2,3-sialic acid at the terminus of biantennary N-glycan was the epitope associated with BD. In this study, we present a novel approach to elucidating the association between BD and glycosylation by tracing isomeric structures containing sialic acid epitopes. Isomer-specific glycan profiling is suitable for analysis of large clinical cohorts and may facilitate the introduction of diagnostic assays for other immune diseases. |
format | Online Article Text |
id | pubmed-8650305 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86503052021-12-08 Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet’s Disease Seo, Nari Lee, Hyunjun Oh, Myung Jin Kim, Ga Hyeon Lee, Sang Gil Ahn, Joong Kyong Cha, Hoon-Suk Kim, Kyoung Heon Kim, Jaehan An, Hyun Joo Front Mol Biosci Molecular Biosciences Behcet’s disease (BD) is an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death. Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity. As the link between glycosylation and the immune system has been revealed, research on the immunological function of glycans is being actively conducted. In particular, sialic acids at the terminus of glycoconjugates are directly implicated in immune responses, cell–cell/pathogen interactions, and tumor progression. Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases. Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans. Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex(5)HexNAc(4)NeuAc(1), Hex(5)HexNAc(4)Fuc(1)NeuAc(1), and Hex(5)HexNAc(4)NeuAc(2). Among them, three isomers almost completely distinguished BD from control with high sensitivity and specificity with an area under the curve (AUC) of 0.945, suggesting the potential as novel BD biomarkers. In particular, it was confirmed that α2,3-sialic acid at the terminus of biantennary N-glycan was the epitope associated with BD. In this study, we present a novel approach to elucidating the association between BD and glycosylation by tracing isomeric structures containing sialic acid epitopes. Isomer-specific glycan profiling is suitable for analysis of large clinical cohorts and may facilitate the introduction of diagnostic assays for other immune diseases. Frontiers Media S.A. 2021-11-23 /pmc/articles/PMC8650305/ /pubmed/34888356 http://dx.doi.org/10.3389/fmolb.2021.778851 Text en Copyright © 2021 Seo, Lee, Oh, Kim, Lee, Ahn, Cha, Kim, Kim and An. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Seo, Nari Lee, Hyunjun Oh, Myung Jin Kim, Ga Hyeon Lee, Sang Gil Ahn, Joong Kyong Cha, Hoon-Suk Kim, Kyoung Heon Kim, Jaehan An, Hyun Joo Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet’s Disease |
title | Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet’s Disease |
title_full | Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet’s Disease |
title_fullStr | Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet’s Disease |
title_full_unstemmed | Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet’s Disease |
title_short | Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet’s Disease |
title_sort | isomer-specific monitoring of sialylated n-glycans reveals association of α2,3-linked sialic acid epitope with behcet’s disease |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650305/ https://www.ncbi.nlm.nih.gov/pubmed/34888356 http://dx.doi.org/10.3389/fmolb.2021.778851 |
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