# Pediatric sepsis inflammatory blood biomarkers that correlate with clinical variables and severity of illness scores

**Authors:** Sean Leonard, Hailey Guertin, Natalya Odoardi, Michael R. Miller, Maitray A. Patel, Mark Daley, Gediminas Cepinskas, Douglas D. Fraser

PMC · DOI: 10.1186/s12950-024-00379-w · Journal of Inflammation (London, England) · 2024-03-07

## TL;DR

This study identifies blood biomarkers that can help detect pediatric sepsis and assess its severity based on clinical data.

## Contribution

The study identifies specific inflammatory biomarkers that strongly correlate with clinical variables and severity scores in pediatric sepsis.

## Key findings

- Nine biomarkers (e.g., IL-6, IL-8) showed high diagnostic accuracy (AUC > 0.9) for pediatric sepsis.
- Six critical biomarkers were identified as most important for sepsis detection using machine learning.
- IL-3 distinguished bacterial from viral infections, and biomarkers correlated with illness severity.

## Abstract

Sepsis is a dysregulated systemic inflammatory response triggered by infection, resulting in organ dysfunction. A major challenge in clinical pediatrics is to identify sepsis early and then quickly intervene to reduce morbidity and mortality. As blood biomarkers hold promise as early sepsis diagnostic tools, we aimed to measure a large number of blood inflammatory biomarkers from pediatric sepsis patients to determine their predictive ability, as well as their correlations with clinical variables and illness severity scores.

Pediatric patients that met sepsis criteria were enrolled, and clinical data and blood samples were collected. Fifty-eight inflammatory plasma biomarker concentrations were determined using immunoassays. The data were analyzed with both conventional statistics and machine learning.

Twenty sepsis patients were enrolled (median age 13 years), with infectious pathogens identified in 75%. Vasopressors were administered to 85% of patients, while 55% received invasive ventilation and 20% were ventilated non-invasively. A total of 24 inflammatory biomarkers were significantly different between sepsis patients and age/sex-matched healthy controls. Nine biomarkers (IL-6, IL-8, MCP-1, M-CSF, IL-1RA, hyaluronan, HSP70, MMP3, and MMP10) yielded AUC parameters > 0.9 (95% CIs: 0.837-1.000; p < 0.001). Boruta feature reduction yielded 6 critical biomarkers with their relative importance: IL-8 (12.2%), MCP-1 (11.6%), HSP70 (11.6%), hyaluronan (11.5%), M-CSF (11.5%), and IL-6 (11.5%); combinations of 2 biomarkers yielded AUC values of 1.00 (95% CI: 1.00–1.00; p < 0.001). Specific biomarkers strongly correlated with illness severity scoring, as well as other clinical variables. IL-3 specifically distinguished bacterial versus viral infection (p < 0.005).

Specific inflammatory biomarkers were identified as markers of pediatric sepsis and strongly correlated to both clinical variables and sepsis severity.

The online version contains supplementary material available at 10.1186/s12950-024-00379-w.

## Linked entities

- **Proteins:** IL6 (interleukin 6), CXCL8 (C-X-C motif chemokine ligand 8), CCL2 (C-C motif chemokine ligand 2), CSF1 (colony stimulating factor 1), IL1R1 (interleukin 1 receptor type 1), HSPA1A (heat shock protein family A (Hsp70) member 1A), MMP3 (matrix metallopeptidase 3), MMP10 (matrix metallopeptidase 10), IL3 (interleukin 3)

## Full-text entities

- **Genes:** CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314] {aka CHDS6, MMP-3, SL-1, STMY, STMY1, STR1}, IL3 (interleukin 3) [NCBI Gene 3562] {aka IL-3, MCGF, MULTI-CSF}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, CSF1 (colony stimulating factor 1) [NCBI Gene 1435] {aka CSF-1, MCSF, PG-M-CSF}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IL1RN (interleukin 1 receptor antagonist) [NCBI Gene 3557] {aka CRMO2, DIRA, ICIL-1RA, IL-1RN, IL-1ra, IL-1ra3}, MMP10 (matrix metallopeptidase 10) [NCBI Gene 4319] {aka SL-2, STMY2}
- **Diseases:** inflammatory (MESH:D007249), organ dysfunction (MESH:D009102), infectious (MESH:D003141), infection (MESH:D007239), Sepsis (MESH:D018805), bacterial versus viral infection (MESH:D014777)
- **Chemicals:** hyaluronan (MESH:D006820)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC10921642/full.md

## References

51 references — full list in the complete paper: https://tomesphere.com/paper/PMC10921642/full.md

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Source: https://tomesphere.com/paper/PMC10921642