# Platelet proteome for predictive diagnosis and differentiation of sepsis and septic shock in pediatric patients

## TL;DR

This study explores platelet proteins to help diagnose and differentiate sepsis and septic shock in children, potentially aiding in better treatment decisions.

## Contribution

The study identifies specific platelet proteins that may serve as biomarkers to distinguish sepsis from septic shock in pediatric patients.

## Key findings

- 316 and 83 differentially expressed proteins were identified in sepsis and septic shock groups, respectively, compared to healthy controls.
- Proteins like VAMP8, VAMP2, Syntaxin-16, and SNAP23 show potential to differentiate sepsis from septic shock.
- Platelet proteomic changes suggest possible biomarkers for sepsis severity stratification.

## Abstract

Platelet hyperreactivity and thrombocytopenia are strongly correlated with elevated mortality rates in sepsis, particularly in cases of septic shock. This study aimed to predict pediatric sepsis and distinguish it from septic shock by profiling the platelet proteome.

We conducted a comparative proteomic analysis of platelet protein expression in five individuals with sepsis, five individuals with septic shock and five healthy subjects, utilizing mass spectrometry (DIA-MS).

Our proteomic analysis identified that 316 and 83 differentially expressed proteins (DEPs) in sepsis and septic shock groups, respectively, each compared to the control group. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis unveiled that the DEPs in patients with clinical spectrum of sepsis severity were associated with molecular functions. Comparative Gene Ontology (GO) analysis of DEPs demonstrated distinct spatial enrichment: while ‘extracellular region’ was the top altered term in sepsis, septic shock patients displayed significant enrichment in ‘extracellular region’ and ‘extracellular space’. KEGG pathway analysis identified enrichment of DEPs in pathways related to ‘Lysosome’. Protein–protein interaction analysis identified that a set of ribosomal proteins S27a (40S), L9 (60S), P0, SA, and S3a could serve as potential discriminators between sepsis and healthy subjects. Crucially, Vesicle-associated membrane protein (VAMP) 8, (VAMP)2, Syntaxin-16 and Synaptosomal-associated protein 23 were identified as key candidates with the potential to distinguish sepsis from septic shock.

These observed proteomic changes could inform the future biomarker identification for sepsis severity stratification. Importantly, these are preliminary findings from a small sample with limited functional assessments, and their clinical utility requires confirmation in independent, larger cohorts.