journal article·2025-09-15Open access

Diagnostic Accuracy of Presepsin, sMR, and Established Inflammatory Biomarkers in Critically Ill Children with Sepsis or Systemic Inflammatory Response Syndrome

Adriana Hadzhieva-Hristova, Daniela Gerova, Sevim Shefket, Mergyul Halilova, Darina Krumova, Temenuga Stoeva, Violeta Iotova

Applied Sciences· Volume 15· Issue 18

Abstract

Background: Pediatric sepsis is a life-threatening emergency and remains complex to diagnose promptly due to the absence of universally reliable biomarkers. C-reactive protein (CRP) and procalcitonin (PCT) are widely used but have limited effectiveness. We evaluated the diagnostic reliability of presepsin and soluble mannose receptor (sMR) and identified optimal biomarker combinations for distinguishing sepsis from non-infectious systemic inflammatory response syndrome (SIRS) in children. Methods: A total of 80 children were enrolled in this prospective study, including 53 consecutive admissions to the pediatric intensive care unit (PICU) (sepsis, n = 42; non-infectious SIRS, n = 11) and 27 healthy controls. The serum levels of new biomarkers presepsin and soluble mannose receptor (sMR) levels were quantified by ELISA methods and their diagnostic reliability (both individually and combined with CRP and PCT) was assessed using receiver operating characteristic (ROC) curves and multivariate logistic regression. Results: Significantly higher concentrations of all measured markers were found both in septic and other critically ill patients than in healthy controls (p < 0.05). No single biomarker reliably differentiated sepsis from non-infectious SIRS. The sMR + CRP + PCT combination demonstrated the highest diagnostic accuracy (AUC = 0.78, p = 0.0007), surpassing the CRP + PCT model (AUC = 0.71, p = 0.0087). Conclusions: The addition of sMR to the established markers CRP and PCT improves the diagnostic effectiveness in pediatric sepsis. Larger multicenter studies are warranted to confirm clinical utility.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Sepsis Diagnosis and Treatment · Neonatal and Maternal Infections · Hemodynamic Monitoring and Therapy

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pediatrics, Medical University of Varna, 9002 Varna, Bulgaria

First Clinic and PICU, University Hospital St. Marina, 9010 Varna, Bulgaria

Department of Clinical Laboratory, Medical University of Varna, 9002 Varna, Bulgaria

Clinical Immunology Laboratory, University Hospital St. Marina, 9010 Varna, Bulgaria

Clinical Laboratory, University Hospital St. Marina, 9010 Varna, Bulgaria

Department of Microbiology and Virology, Medical University of Varna, 9002 Varna, Bulgaria

Microbiology Laboratory, University Hospital St. Marina, 9010 Varna, Bulgaria

Funding

Fund “Science” of the Medical University of Varna

References (35)

Show source-provided references
1. Global, regional, and national sepsis incidence and mortality, 1990–2017: Analysis for the Global Burden of Disease Study10.1016/S0140-6736(19)32989-7 ↗
2. Operationalizing Appropriate Sepsis Definitions in Children Worldwide: Considerations for the Pediatric Sepsis Definition Taskforce10.1097/PCC.0000000000003263 ↗
3. Biomarkers of sepsis: Time for a reappraisal10.1186/s13054-020-02993-5 ↗
4. Cicchinelli, S., Pignataro, G., Gemma, S., Piccioni, A., Picozzi, D., Ojetti, V., Franceschi, F., and Candelli, M. (2024). PAMPs and DAMPs in Sepsis: A Review of Their Molecular Features and Potential Clinical Implications. Int. J. Mol. Sci., 25.10.3390/ijms25020962 ↗
5. Pathogen- and Danger-Associated Molecular Patterns and the Cytokine Response in Sepsis10.1089/sur.2017.264 ↗
6. Host response biomarkers in the diagnosis of sepsis: A general overview10.1007/978-1-4939-1776-1_15 ↗
7. Slaats, J., Ten Oever, J., Van De Veerdonk, F.L., and Netea, M.G. (2016). IL-1β/IL-6/CRP and IL-18/ferritin: Distinct Inflammatory Programs in Infections. PLoS Pathog., 12.10.1371/journal.ppat.1005973 ↗
8. C-reactive protein and other biomarkers—The sense and non-sense of using inflammation biomarkers for the diagnosis of severe bacterial infection10.14785/lymphosign-2018-0001 ↗
9. Biomarkers to guide sepsis management10.1186/s13613-025-01524-1 ↗
10. Presepsin (sCD14-ST), an innate immune response marker in sepsis10.1016/j.cca.2015.06.026 ↗
11. A soluble form of the macrophage-related mannose receptor (MR/CD206) is present in human serum and elevated in critical illness10.1515/cclm-2013-0451 ↗
12. Individual and combined bioscore model of presepsin, procalcitonin, and high sensitive C—Reactive protein as biomarkers for early diagnosis of paediatric sepsis10.1016/j.heliyon.2020.e04841 ↗
13. International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics10.1097/01.PCC.0000149131.72248.E6 ↗
14. Baudelet, J.B., and Leteutre, S. (2023, August 31). PELOD-2 Score Calulator [Internet]. ESPNIC. Available online: https://www.espnic.eu/education/clinical-tools/.
15. Schlapbach, L. (2024, March 07). Phoenix Sepsis Score Calculator [Internet]. MDCalc. Available online: https://www.mdcalc.com/calc/10509/phoenix-sepsis-score?uuid=4d87fb25-7ec7-4a93-bdf5-0c10fffc049f&utm_source=mdcalc.
16. Referenzbereiche in der Hämatologie10.1024/0040-5930.63.1.5 ↗
17. Validation of the “Step-by-Step” Approach in the Management of Young Febrile Infants10.1542/peds.2015-4381 ↗
18. A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections10.1001/jamapediatrics.2018.5501 ↗
19. Diagnostic test accuracy of procalcitonin and C-reactive protein for predicting invasive and serious bacterial infections in young febrile infants: A systematic review and meta-analysis10.1016/S2352-4642(24)00021-X ↗
21. The meaning and use of the area under a receiver operating characteristic (ROC) curve10.1148/radiology.143.1.7063747 ↗
22. Reference intervals: An update10.1016/S0009-8981(03)00133-5 ↗
23. Is There a Role of Presepsin as a Novel Biomarker in Pediatric Sepsis?10.5005/jp-journals-10071-24202 ↗
24. Hassuna, N.A., Elgezawy, E., Mousa, S.O., AbdelAziz, R.A., Ibrahem, R.A., Wahed, W.Y.A., Nasif, K.A., and Hefzy, E.M. (2021). Diagnostic value of monocyte chemoattractant Protein-1, soluble mannose receptor, Presepsin, and Procalcitonin in critically ill children admitted with suspected sepsis. BMC Pediatr., 21.10.1186/s12887-021-02930-7 ↗
25. The ability of Procalcitonin, lactate, white blood cell count and neutrophil-lymphocyte count ratio to predict blood stream infection. Analysis of a large database10.1016/j.jcrc.2020.07.026 ↗
26. De Rop, L., De Burghgraeve, T., De Sutter, A., Buntinx, F., and Verbakel, J.Y. (2022). Point-of-care C-reactive protein test results in acute infections in children in primary care: An observational study. BMC Pediatr., 22.10.1186/s12887-022-03677-5 ↗
27. Pontrelli, G., De Crescenzo, F., Buzzetti, R., Jenkner, A., Balduzzi, S., Carducci, F.C., Amodio, D., De Luca, M., Chiurchiù, S., and Davies, E.H. (2017). Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: A meta-analysis. BMC Infect Dis., 17.10.1186/s12879-017-2396-7 ↗
28. Procalcitonin and C-reactive protein as markers of bacterial infection in critically ill children at onset of systemic inflammatory response syndrome10.1097/PCC.0b013e31817285a6 ↗
29. A Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: The Optimizing Antibiotic Strategies in Sepsis (OASIS) Study
30. Utility of Procalcitonin as a Biomarker for Sepsis in Children10.1128/JCM.01851-19 ↗
31. Procalcitonin does discriminate between sepsis and systemic inflammatory response syndrome10.1136/adc.2005.077446 ↗
32. Sepsis and Septic Shock10.1056/NEJMra2403213 ↗
33. Diagnostic Value of Presepsin for Sepsis: A Systematic Review and Meta-Analysis10.1097/MD.0000000000002158 ↗
34. The macrophage activation marker sMR as a diagnostic and prognostic marker in patients with acute infectious disease with or without sepsis10.1080/00365513.2018.1431841 ↗
35. Van Der Zande, H.J.P., Nitsche, D., Schlautmann, L., Guigas, B., and Burgdorf, S. (2021). The Mannose Receptor: From Endocytic Receptor and Biomarker to Regulator of (Meta)Inflammation. Front. Immunol., 12.10.3389/fimmu.2021.765034 ↗