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Glycoproteoform Profiles of Individual Patients’ Plasma Alpha-1-Antichymotrypsin are Unique and Extensively Remodeled Following a Septic Episode

Sepsis and septic shock remain the leading causes of death in intensive care units (ICUs), yet the pathogenesis originating from the inflammatory response during sepsis remains ambiguous. Acute-phase proteins are typically highly glycosylated, and the nature of the glycans have been linked to the in...

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Autores principales: Čaval, Tomislav, Lin, Yu-Hsien, Varkila, Meri, Reiding, Karli R., Bonten, Marc J. M., Cremer, Olaf L., Franc, Vojtech, Heck, Albert J. R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840657/
https://www.ncbi.nlm.nih.gov/pubmed/33519818
http://dx.doi.org/10.3389/fimmu.2020.608466
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author Čaval, Tomislav
Lin, Yu-Hsien
Varkila, Meri
Reiding, Karli R.
Bonten, Marc J. M.
Cremer, Olaf L.
Franc, Vojtech
Heck, Albert J. R.
author_facet Čaval, Tomislav
Lin, Yu-Hsien
Varkila, Meri
Reiding, Karli R.
Bonten, Marc J. M.
Cremer, Olaf L.
Franc, Vojtech
Heck, Albert J. R.
author_sort Čaval, Tomislav
collection PubMed
description Sepsis and septic shock remain the leading causes of death in intensive care units (ICUs), yet the pathogenesis originating from the inflammatory response during sepsis remains ambiguous. Acute-phase proteins are typically highly glycosylated, and the nature of the glycans have been linked to the incidence and severity of such inflammatory responses. To further build upon these findings we here monitored, the longitudinal changes in the plasma proteome and, in molecular detail, glycoproteoform profiles of alpha-1-antichymotrypsin (AACT) extracted from plasma of ten individual septic patients. For each patient we included four different time-points, including post-operative (before sepsis) and following discharge from the ICU. We isolated AACT from plasma depleted for albumin, IgG and serotransferrin and used high-resolution native mass spectrometry to qualitatively and quantitatively monitor the multifaceted glycan microheterogeneity of desialylated AACT, which allowed us to monitor how changes in the glycoproteoform profiles reflected the patient’s physiological state. Although we observed a general trend in the remodeling of the AACT glycoproteoform profiles, e.g. increased fucosylation and branching/LacNAc elongation, each patient exhibited unique features and responses, providing a resilient proof-of-concept for the importance of personalized longitudinal glycoproteoform profiling. Importantly, we observed that the AACT glycoproteoform changes induced by sepsis did not readily subside after discharge from ICU.
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spelling pubmed-78406572021-01-29 Glycoproteoform Profiles of Individual Patients’ Plasma Alpha-1-Antichymotrypsin are Unique and Extensively Remodeled Following a Septic Episode Čaval, Tomislav Lin, Yu-Hsien Varkila, Meri Reiding, Karli R. Bonten, Marc J. M. Cremer, Olaf L. Franc, Vojtech Heck, Albert J. R. Front Immunol Immunology Sepsis and septic shock remain the leading causes of death in intensive care units (ICUs), yet the pathogenesis originating from the inflammatory response during sepsis remains ambiguous. Acute-phase proteins are typically highly glycosylated, and the nature of the glycans have been linked to the incidence and severity of such inflammatory responses. To further build upon these findings we here monitored, the longitudinal changes in the plasma proteome and, in molecular detail, glycoproteoform profiles of alpha-1-antichymotrypsin (AACT) extracted from plasma of ten individual septic patients. For each patient we included four different time-points, including post-operative (before sepsis) and following discharge from the ICU. We isolated AACT from plasma depleted for albumin, IgG and serotransferrin and used high-resolution native mass spectrometry to qualitatively and quantitatively monitor the multifaceted glycan microheterogeneity of desialylated AACT, which allowed us to monitor how changes in the glycoproteoform profiles reflected the patient’s physiological state. Although we observed a general trend in the remodeling of the AACT glycoproteoform profiles, e.g. increased fucosylation and branching/LacNAc elongation, each patient exhibited unique features and responses, providing a resilient proof-of-concept for the importance of personalized longitudinal glycoproteoform profiling. Importantly, we observed that the AACT glycoproteoform changes induced by sepsis did not readily subside after discharge from ICU. Frontiers Media S.A. 2021-01-14 /pmc/articles/PMC7840657/ /pubmed/33519818 http://dx.doi.org/10.3389/fimmu.2020.608466 Text en Copyright © 2021 Čaval, Lin, Varkila, Reiding, Bonten, Cremer, Franc and Heck http://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 Immunology
Čaval, Tomislav
Lin, Yu-Hsien
Varkila, Meri
Reiding, Karli R.
Bonten, Marc J. M.
Cremer, Olaf L.
Franc, Vojtech
Heck, Albert J. R.
Glycoproteoform Profiles of Individual Patients’ Plasma Alpha-1-Antichymotrypsin are Unique and Extensively Remodeled Following a Septic Episode
title Glycoproteoform Profiles of Individual Patients’ Plasma Alpha-1-Antichymotrypsin are Unique and Extensively Remodeled Following a Septic Episode
title_full Glycoproteoform Profiles of Individual Patients’ Plasma Alpha-1-Antichymotrypsin are Unique and Extensively Remodeled Following a Septic Episode
title_fullStr Glycoproteoform Profiles of Individual Patients’ Plasma Alpha-1-Antichymotrypsin are Unique and Extensively Remodeled Following a Septic Episode
title_full_unstemmed Glycoproteoform Profiles of Individual Patients’ Plasma Alpha-1-Antichymotrypsin are Unique and Extensively Remodeled Following a Septic Episode
title_short Glycoproteoform Profiles of Individual Patients’ Plasma Alpha-1-Antichymotrypsin are Unique and Extensively Remodeled Following a Septic Episode
title_sort glycoproteoform profiles of individual patients’ plasma alpha-1-antichymotrypsin are unique and extensively remodeled following a septic episode
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840657/
https://www.ncbi.nlm.nih.gov/pubmed/33519818
http://dx.doi.org/10.3389/fimmu.2020.608466
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