Proteomic biomarkers for early diagnosis and prognosis in pediatric sepsis

<h4>Background</h4>Early diagnosis of pediatric sepsis is difficult because of the lack of specific clinical signs and limitations of standard biomarkers. Proteomics is a promising approach because it can identify disease-specific protein signatures.<h4>Aim</h4>To systematically evaluate the current literature on the application of proteomics in pediatric sepsis, review and evaluate the current evidence on proteomic biomarkers for diagnosing and predicting pediatric sepsis.<h4>Methods</h4>This is a systematic review with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-informed, structured search and transparent study-selection reporting. A structured literature search was conducted in PubMed, Scopus, and Web of Science up to January 2025. Studies involving pediatric patients (ages 0-18) with sepsis that used proteomic platforms and reported diagnostic or prognostic outcomes were included.<h4>Results</h4>Four studies met the inclusion criteria. Identified biomarkers included interleukin-27, signal transducer and activator of transcription 3, haptoglobin, serum amyloid A 1/2, soluble CD25, and leucine-rich alpha-2-glycoprotein 1. Sensitivities ranged from 60% to 86%, and specificities ranged from 75% to 92%. Multi-marker panels demonstrated superior diagnostic performance compared to single markers. Biomarkers were detectable within 2-6 hours of symptom onset. The analytical methods used varied and included enzyme-linked immunosorbent assays, liquid chromatography-tandem mass spectrometry, and SOMAscan. Most studies were exploratory and lacked external validation; they also used small, heterogeneous cohorts.<h4>Conclusion</h4>Proteomics shows promise for earlier and more precise diagnostics of pediatric sepsis, but clinical translation is limited by small, single-center cohorts; age-dependent variability without developmental reference ranges; scarce longitudinal profiling; and minimal external validation. The priority now is multicenter, age-stratified, longitudinal studies with real-world comparators.