Abstract
OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.