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...

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Autores principales: Nari Seo, Hyunjun Lee, Myung Jin Oh, Ga Hyeon Kim, Sang Gil Lee, Joong Kyong Ahn, Hoon-Suk Cha, Kyoung Heon Kim, Jaehan Kim, Hyun Joo An
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:2d76a90a6cee48c290c36f30460a69522021-11-30T13:22:38ZIsomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet’s Disease2296-889X10.3389/fmolb.2021.778851https://doaj.org/article/2d76a90a6cee48c290c36f30460a69522021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.778851/fullhttps://doaj.org/toc/2296-889XBehcet’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 Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2. 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.Nari SeoNari SeoHyunjun LeeMyung Jin OhMyung Jin OhGa Hyeon KimGa Hyeon KimSang Gil LeeSang Gil LeeJoong Kyong AhnHoon-Suk ChaKyoung Heon KimJaehan KimHyun Joo AnHyun Joo AnFrontiers Media S.A.articleBehcet’s diseaseglycan isomersialic acid epitopequantitationbiomarkerBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution DOAJ
collection DOAJ
language EN
topic Behcet’s disease
glycan isomer
sialic acid epitope
quantitation
biomarker
Biology (General)
QH301-705.5
spellingShingle Behcet’s disease
glycan isomer
sialic acid epitope
quantitation
biomarker
Biology (General)
QH301-705.5
Nari Seo
Nari Seo
Hyunjun Lee
Myung Jin Oh
Myung Jin Oh
Ga Hyeon Kim
Ga Hyeon Kim
Sang Gil Lee
Sang Gil Lee
Joong Kyong Ahn
Hoon-Suk Cha
Kyoung Heon Kim
Jaehan Kim
Hyun Joo An
Hyun Joo An
Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet’s Disease
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 Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2. 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 article
author Nari Seo
Nari Seo
Hyunjun Lee
Myung Jin Oh
Myung Jin Oh
Ga Hyeon Kim
Ga Hyeon Kim
Sang Gil Lee
Sang Gil Lee
Joong Kyong Ahn
Hoon-Suk Cha
Kyoung Heon Kim
Jaehan Kim
Hyun Joo An
Hyun Joo An
author_facet Nari Seo
Nari Seo
Hyunjun Lee
Myung Jin Oh
Myung Jin Oh
Ga Hyeon Kim
Ga Hyeon Kim
Sang Gil Lee
Sang Gil Lee
Joong Kyong Ahn
Hoon-Suk Cha
Kyoung Heon Kim
Jaehan Kim
Hyun Joo An
Hyun Joo An
author_sort Nari Seo
title 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_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_sort isomer-specific monitoring of sialylated n-glycans reveals association of α2,3-linked sialic acid epitope with behcet’s disease
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/2d76a90a6cee48c290c36f30460a6952
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