Targeted biomarker discovery by high throughput glycosylation profiling of human plasma alpha1-antitrypsin and immunoglobulin A.

Protein N-glycosylation patterns are known to show vast genetic as well as physiological and pathological variation and represent a large pool of potential biomarkers. Large-scale studies are needed for the identification and validation of biomarkers, and the analytical techniques required have rece...

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Autores principales:	L Renee Ruhaak, Carolien A M Koeleman, Hae-Won Uh, Jord C Stam, Diana van Heemst, Andrea B Maier, Jeanine J Houwing-Duistermaat, Paul J Hensbergen, P Eline Slagboom, André M Deelder, Manfred Wuhrer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8b0bcfa75e27459b97fd9da91588f83d
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spelling	oai:doaj.org-article:8b0bcfa75e27459b97fd9da91588f83d2021-11-18T08:56:21ZTargeted biomarker discovery by high throughput glycosylation profiling of human plasma alpha1-antitrypsin and immunoglobulin A.1932-620310.1371/journal.pone.0073082https://doaj.org/article/8b0bcfa75e27459b97fd9da91588f83d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24039863/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Protein N-glycosylation patterns are known to show vast genetic as well as physiological and pathological variation and represent a large pool of potential biomarkers. Large-scale studies are needed for the identification and validation of biomarkers, and the analytical techniques required have recently been developed. Such methods have up to now mainly been applied to complex mixtures of glycoproteins in biofluids (e.g. plasma). Here, we analyzed N-glycosylation profiles of alpha1-antitrypsin (AAT) and immunoglobulin A (IgA) enriched fractions by 96-well microtitration plate based high-throughput immuno-affinity capturing and N-glycan analysis using multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (CGE-LIF). Human plasma samples were from the Leiden Longevity Study comprising 2415 participants of different chronological and biological ages. Glycosylation patterns of AAT enriched fractions were found to be associated with chronological (calendar) age and they differed between females and males. Moreover, several glycans in the AAT enriched fraction were associated with physiological parameters marking cardiovascular and metabolic diseases. Pronounced differences were found between males and females in the glycosylation profiles of IgA enriched fractions. Our results demonstrate that large-scale immuno-affinity capturing of proteins from human plasma using a bead-based method combined with high-throughput N-glycan analysis is a powerful tool for the discovery of glycosylation-based biomarker candidates.L Renee RuhaakCarolien A M KoelemanHae-Won UhJord C StamDiana van HeemstAndrea B MaierJeanine J Houwing-DuistermaatPaul J HensbergenP Eline SlagboomAndré M DeelderManfred WuhrerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e73082 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q L Renee Ruhaak Carolien A M Koeleman Hae-Won Uh Jord C Stam Diana van Heemst Andrea B Maier Jeanine J Houwing-Duistermaat Paul J Hensbergen P Eline Slagboom André M Deelder Manfred Wuhrer Targeted biomarker discovery by high throughput glycosylation profiling of human plasma alpha1-antitrypsin and immunoglobulin A.
description	Protein N-glycosylation patterns are known to show vast genetic as well as physiological and pathological variation and represent a large pool of potential biomarkers. Large-scale studies are needed for the identification and validation of biomarkers, and the analytical techniques required have recently been developed. Such methods have up to now mainly been applied to complex mixtures of glycoproteins in biofluids (e.g. plasma). Here, we analyzed N-glycosylation profiles of alpha1-antitrypsin (AAT) and immunoglobulin A (IgA) enriched fractions by 96-well microtitration plate based high-throughput immuno-affinity capturing and N-glycan analysis using multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (CGE-LIF). Human plasma samples were from the Leiden Longevity Study comprising 2415 participants of different chronological and biological ages. Glycosylation patterns of AAT enriched fractions were found to be associated with chronological (calendar) age and they differed between females and males. Moreover, several glycans in the AAT enriched fraction were associated with physiological parameters marking cardiovascular and metabolic diseases. Pronounced differences were found between males and females in the glycosylation profiles of IgA enriched fractions. Our results demonstrate that large-scale immuno-affinity capturing of proteins from human plasma using a bead-based method combined with high-throughput N-glycan analysis is a powerful tool for the discovery of glycosylation-based biomarker candidates.
format	article
author	L Renee Ruhaak Carolien A M Koeleman Hae-Won Uh Jord C Stam Diana van Heemst Andrea B Maier Jeanine J Houwing-Duistermaat Paul J Hensbergen P Eline Slagboom André M Deelder Manfred Wuhrer
author_facet	L Renee Ruhaak Carolien A M Koeleman Hae-Won Uh Jord C Stam Diana van Heemst Andrea B Maier Jeanine J Houwing-Duistermaat Paul J Hensbergen P Eline Slagboom André M Deelder Manfred Wuhrer
author_sort	L Renee Ruhaak
title	Targeted biomarker discovery by high throughput glycosylation profiling of human plasma alpha1-antitrypsin and immunoglobulin A.
title_short	Targeted biomarker discovery by high throughput glycosylation profiling of human plasma alpha1-antitrypsin and immunoglobulin A.
title_full	Targeted biomarker discovery by high throughput glycosylation profiling of human plasma alpha1-antitrypsin and immunoglobulin A.
title_fullStr	Targeted biomarker discovery by high throughput glycosylation profiling of human plasma alpha1-antitrypsin and immunoglobulin A.
title_full_unstemmed	Targeted biomarker discovery by high throughput glycosylation profiling of human plasma alpha1-antitrypsin and immunoglobulin A.
title_sort	targeted biomarker discovery by high throughput glycosylation profiling of human plasma alpha1-antitrypsin and immunoglobulin a.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/8b0bcfa75e27459b97fd9da91588f83d
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Targeted biomarker discovery by high throughput glycosylation profiling of human plasma alpha1-antitrypsin and immunoglobulin A.

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