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Systematic Reviews
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World J Clin Pediatr. Mar 9, 2026; 15(1): 114054
Published online Mar 9, 2026. doi: 10.5409/wjcp.v15.i1.114054
Proteomic biomarkers for early diagnosis and prognosis in pediatric sepsis
Guldana Sabitova, Zhalaliddin Makhammajanov, Marina Khvan, Pavel Tarlykov, Vitaliy Sazonov
Guldana Sabitova, Zhalaliddin Makhammajanov, Marina Khvan, Department of Medicine, School of Medicine, Nazarbayev University, Astana Z05K4F4, Kazakhstan
Pavel Tarlykov, Department of Proteomics and Mass Spectrometry, National Center for Biotechnology, Astana Z05K4F4, Kazakhstan
Vitaliy Sazonov, Department of Surgery, School of Medicine, Nazarbayev University, Astana Z05K4F4, Kazakhstan
Vitaliy Sazonov, Pediatric Anesthesiology and Intensive Care Unit, Mother and Child Center, University Medical Center, Astana Z05K4F4, Kazakhstan
Author contributions: Sabitova G wrote the original draft; Sabitova G and Sazonov V designed the research study; Makhammajanov Z was responsible for developing the methodology; Makhammajanov Z and Sazonov V participated in the review and editing; Khvan M and Tarlykov P participated in the formal analysis and investigation; all authors have read and approved the submitted version.
Supported by Nazarbayev University Faculty Development Grant for 2025-2027, No. 040225FD4716.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Vitaliy Sazonov, MD, Assistant Professor, Department of Surgery, School of Medicine, Nazarbayev University, Kabanbay Batyr 53, Astana Z05K4F4, Kazakhstan. vitaliy.sazonov@nu.edu.kz
Received: September 11, 2025
Revised: September 29, 2025
Accepted: November 24, 2025
Published online: March 9, 2026
Processing time: 177 Days and 4 Hours
Abstract
BACKGROUND

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.

AIM

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Keywords: Sepsis; Pediatric sepsis; Biomarkers; Proteomics; Multi-omics; Pediatric intensive care unit; Pediatrics

Core Tip: Pediatric sepsis requires rapid and reliable “rule-in” tools upon presentation. This systematic review summarizes four pediatric proteomics studies and presents a practical pathway. Single markers, such as interleukin-27, serum amyloid A 1, soluble CD25, and leucine-rich alpha-2-glycoprotein 1, demonstrate high specificity for early diagnosis. The infant-focused combination of haptoglobin and thrombospondin 1 improves short-term risk stratification. We explain why age matters: Noting that immune maturation shifts effect sizes and may necessitate age-adjusted cut-points and neonatal-specific panels. We also map discovery platforms (aptamer/mass spectrometry) to rapid 3-5-plex immunoassays that are suitable for emergency department and pediatric intensive care unit use. Rather than offering pooled estimates, the systematic review provides translational guidance aimed at accelerating the deployment of clinically useful pediatric sepsis testing.