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Development of Cereblon (CRBN) as an early prognostic biomarker in Paediatric Sepsis: a Prospective Observational
Namita Mishra1, Ankit Gupta2, Rasna Gupta3
1Pediatrics, All India Institute of Medical Sciences Raebareli, Raebareli, Uttar Pradesh, India namitam23@gmail.com.
Insights
This study investigates Cereblon (CRBN) as a novel biomarker for predicting outcomes in pediatric sepsis. Elevated CRBN levels may help identify children at higher risk, improving early intervention and patient survival.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Biomarker discovery
Background:
- Pediatric sepsis is a major cause of child mortality, particularly in resource-limited areas.
- Current prognostic tools for pediatric sepsis lack specificity and broad applicability.
- Cereblon (CRBN), involved in immune modulation, has an unexplored role in pediatric sepsis outcomes.
Purpose of the Study:
- To evaluate Cereblon (CRBN) expression as an early prognostic biomarker in pediatric sepsis.
- To determine the correlation of CRBN with disease severity and clinical outcomes.
- To inform clinical decision-making for improved pediatric sepsis management.
Main Methods:
- Prospective observational study of 240 children (2 months–15 years) with sepsis in a PICU.
- Assessed CRBN mRNA and protein levels via qPCR and ELISA at admission.
- Correlated CRBN with 28-day mortality, pSOFA scores, CRP, and clinical outcomes; analyzed using ROC curves.
Main Results:
- CRBN levels will be compared between survivors and non-survivors.
- Correlation analysis will assess the relationship between CRBN, pSOFA, CRP, and clinical outcomes.
- Prognostic performance of CRBN will be determined using ROC analysis and AUC values.
Conclusions:
- CRBN shows potential as a novel early prognostic biomarker for pediatric sepsis.
- Identifying high-risk children through CRBN can guide timely interventions.
- This research may lead to improved management strategies and outcomes for pediatric sepsis.
Introduction:
Paediatric sepsis remains a formidable challenge in global child health, contributing significantly to morbidity and mortality, especially in resource-constrained settings. Accurate early prognostication of disease trajectory is imperative for effective triage and timely intervention; however, existing biomarkers and clinical scoring systems are often limited by insufficient specificity, operational complexity or limited applicability across diverse clinical settings. One potential avenue for improving early prognostication is investigating novel biomarkers. Cereblon (CRBN), a multifunctional protein implicated in immune modulation, has shown variable associations with outcomes in adult sepsis, while its role in paediatric sepsis remains unexplored. This study aims to assess the potential of CRBN expression as an early prognostic biomarker in paediatric sepsis, thereby informing clinical decision-making and improving patient outcomes.
Methods And Analysis:
This prospective observational paediatric intensive care unit (PICU)-based study will enrol 240 children aged 2 months to 15 years with sepsis using a consecutive non-probability sampling method. Pediatric Sequential Organ Failure Assessment (pSOFA) scores will be recorded at admission and at 24 hours. Blood samples will be collected at admission to assess CRBN mRNA expression by quantitative real-time PCR and protein levels by ELISA. The primary outcome will be the correlation of CRBN with 28-day mortality. Secondary outcomes will assess its correlation with the pSOFA score, C-reactive protein, duration of mechanical ventilation and duration of PICU stay. CRBN levels will be compared between survivors and non-survivors, and correlations with pSOFA score, inflammatory markers and clinical outcomes will be assessed using Pearson's or Spearman's tests as appropriate. Prognostic performance will be assessed using Receiver operating characteristics (ROC) curve and area under curve (AUC) value with Youden-derived cut-offs. Multivariable regression will be performed to adjust for key confounders.
Ethics And Dissemination:
Ethical approval was obtained from the Institutional Ethics Committee, All India Institute of Medical Sciences, Raebareli, prior to study initiation (IEC Code-2024-4-EMP-EXP-9). Written informed consent will be obtained from parents or guardians. The study findings will be disseminated through peer-reviewed publications and scientific conferences. The reporting of study results will adhere to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines to ensure transparency and completeness.