Serum AGP-1-Leˣ Glycoforms report on survivorship of patients with septic shock upon admission to intensive care unit
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Date
2026
Authors
Chau, T.H.
Chatterjee, S.
Caulfield, L.
Chernykh, A.
Traini, M.
Fehring, J.
Hwang, H.
Kawahara, R.
Meyer, E.J.
Torpy, D.J.
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Journal article
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Molecular & Cellular Proteomics, 2026; 25(1):101470-1-101470-18
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The Huong Chau, Sayantani Chatterjee, Liam Caulfield, Anastasia Chernykh, Mathew Traini, Joshua Fehring, Heeyoun Hwang, Rebeca Kawahara, Emily J. Meyer, David J. Torpy, and Morten Thaysen-Andersen
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Abstract
Septic shock, the excessive immune response to pathogen infection, accounts globally for ∼20% of all deaths. Current methods to establish disease severity are unacceptably slow, unspecific, and insensitive, hindering timely and effective treatment. Aiming to establish easy-to-measure glyco-signatures that may identify the most critically unwell patients, we applied comparative glycomics and glycoproteomics to sera longitudinally collected from septic shock survivors (n = 29) and nonsurvivors (n = 8). Glycomics of all 134 serum samples (sampled daily until recovery/death) revealed significant N-glycome dynamics across both patient groups. Unsupervised clustering of the serum N-glycome measured upon intensive care unit (ICU) admission (day 1) indicated survivorship-specific glyco-signatures. We therefore employed machine learning to train a random forest model using the serum N-glycome data. The model accurately classified survivorship outcomes of 35 of 37 patients (accuracy 94.6%) and correctly predicted 29 of 29 survivors (specificity 100%) and six of eight nonsurvivors (sensitivity 75%). Interrogation of the serum N-glycome data revealed that Lewis x (Lex)-type N-glycans are elevated in nonsurvivors relative to survivors at ICU admission, a finding recapitulated by glycoproteomics. Among the 58 other Lex-containing serum glycoproteins that were strongly associated with acute phase response and stress pathways, alpha-1-acid-glycoprotein (AGP-1) was identified as a principal carrier of Lex glycoepitopes with a potential to stratify septic shock survivors from nonsurvivors (AUC 0.90). This study lays a foundation for risk stratification of septic shock patients by uncovering easy-to-assay AGP-1-Lex glycoforms that identify individuals experiencing poor survival outcomes already upon ICU admission, with the potential to translate to early individualized clinical care at the bedside.
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© 2025 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/).