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Serum AGP-1-sLex glycoforms report on survivorship of patients with septic shock upon admission to intensive care unit

ABSTRACT: Septic shock, the excessive host immune response to pathogen infection, poses a major health concern accounting globally for approximately 20% of all deaths. Current methods to establish disease severity are unacceptably slow, unspecific and insensitive, hindering timely and effective treatment and patient care. Aiming to identify easy-to-assay glyco-signatures that may identify and guide the clinical management of the worst affected patients, we applied quantitative glycomics and glycoproteomics to serum longitudinally collected from septic shock survivors (n = 29) and non-survivors (n = 8). Glycomics of all 134 serum samples (2-7 samples/patient, daily sampling until recovery or death) revealed significant N-glycome dynamics in both septic shock survivors and non-survivors. Interestingly, unsupervised clustering of the serum N-glycome upon ICU admission (day 1) indicated survivorship-specific glyco-signatures. We therefore trained a random forest model using the serum N-glycome data from all ICU samples except for day 1 and tested the model using the clinically informative day 1 data. Excitingly, the model accurately classified survivorship outcomes of 35 of 37 patients (specificity 94.6%) and correctly predicted 6 of 8 non-survivors (sensitivity 75%). Targeted N-glycome analysis revealed raised levels of Lewis fucosylation in non-survivors relative to survivors already upon ICU admission. Elevated Lewis fucosylation was recapitulated by comparative glycoproteomics that also identified α-1-acid-glycoprotein as the principal carrier of Lewis fucosylation. Enabled by integrated -omics approaches, this study has laid a foundation for improved clinical management of septic shock patients by uncovering easy-to-assay glyco-signatures that early in the disease course accurately identify individuals with poor survival outcomes.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

DISEASE(S): Bacterial Sepsis,Septic Shock

SUBMITTER: The Huong Chau

LAB HEAD: Morten Thaysen-Andersen

PROVIDER: PXD065024 | Pride | 2025-11-17

REPOSITORIES: Pride

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Source:

			Action	DRS
	20231129_RK_Enriched_NS-1.raw	Raw
	20231129_RK_Enriched_NS-1_Byonic_512.csv	Csv
	20231129_RK_Enriched_NS-1_Byonic_Broad.csv	Csv
	20231129_RK_Enriched_NS-2.raw	Raw
	20231129_RK_Enriched_NS-2_Byonic_512.csv	Csv

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Project description:Background: As early and appropriate care of severe septic patients is associated with better outcome, understanding of very first events in the disease process is needed. Pan-genomic analyses offer an interesting opportunity to study global genomic response within the very first hours after sepsis. The objective of this study was to investigate the systemic genomic response in severe Intensive Care Unit (ICU) patients and determine whether patterns of gene expression could be associated with clinical severity evaluated by severity score. Methods: Twenty-eight ICU patients were enrolled at the onset of septic shock. Blood samples were collected within 30 minutes, 24 and 48 hours after shock and genomic response was evaluated using microarrays. The genome wide expression pattern of blood leukocytes was sequentially compared to healthy volunteers and after stratification based on SAPSII score to identify potential mechanisms of dysregulation. Results: Septic shock induces a global reprogramming of the whole leukocyte transcriptome affecting multiple functions and pathways (> 71% of the whole genome was modified). Most altered pathways were not significantly different between SAPSII-high and SAPSII-low groups of patients. However the magnitude and the duration of these alterations were different between these two groups. Importantly, we observed that the more severe patients did not exhibit the strongest modulation. This indicates that some regulation mechanisms leading to recovery seem to take place at early stage. Conclusion: In conclusion, both pro- and anti-inflammatory processes, measured at the transcriptomic level, are induced within the very first hours after septic shock. Interestingly, the more severe patients did not exhibit the strongest modulation. This highlights that, not only the responses mechanisms by themself but mainly their early and appropriate regulation, are crucial for patient recovery. This reinforces the idea that an immediate and tailored aggressive care of patients, aimed at restoring an appropriately regulated immune response, may have a beneficial impact on outcome. Twenty-eight ICU patients were enrolled at the onset of septic shock. Blood samples were collected within 30 minutes, 24 and 48 hours after septic shock and compared to twenty-five healthy volunteers

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Serum AGP-1-sLex glycoforms report on survivorship of patients with septic shock upon admission to intensive care unit

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