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Monocytic Human Leukocyte Antigen-DR Expression Levels to Predict Outcome in Children With Severe Sepsis
Nanmaaran Periyannan Thangavel1, Narayanan Parameswaran1, Prabhu Manivannan2
1Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
Insights
Monocytic Human Leukocyte Antigen-DR (mHLA-DR) expression was lower in children with severe sepsis who died compared to survivors. This finding suggests mHLA-DR may serve as a biomarker for immune paralysis in pediatric sepsis.
Area of Science:
- Immunology
- Pediatric Critical Care
- Sepsis Research
Background:
- Severe sepsis in children is a life-threatening condition with significant mortality.
- Assessing immune status is crucial for predicting outcomes in pediatric sepsis.
- Monocytic Human Leukocyte Antigen-DR (mHLA-DR) expression is a marker of immune cell activation.
Purpose of the Study:
- To investigate the association between mHLA-DR expression and outcomes in children with severe sepsis.
- To determine if mHLA-DR levels can predict mortality in pediatric severe sepsis.
- To explore the relationship between mHLA-DR and immune paralysis in pediatric sepsis.
Main Methods:
- A cohort of children aged 29 days to 15 years admitted to the pediatric intensive care unit (PICU) with severe sepsis or septic shock were enrolled.
- mHLA-DR expression (antigen bound per cell - ABC) was measured at two time points during PICU stay (P1: 72–120 hours, P2: 121–168 hours).
- The difference between time points (delta mHLA-DR) and outcomes (survival, mortality, secondary infection) were analyzed.
Main Results:
- Children who survived severe sepsis had significantly higher median mHLA-DR levels at both P1 (7409 vs. 2509, P=0.004) and P2 (14728 vs. 2085, P=0.001) compared to those who expired.
- The delta mHLA-DR was also significantly higher in survivors (4574 vs. 309, P=0.012).
- mHLA-DR levels at P1, P2, and delta mHLA-DR were associated with mortality but not secondary infections. A cutoff of <6631 at P2 predicted mortality with high accuracy (AUC=0.966).
Conclusions:
- Lower mHLA-DR expression in children with severe sepsis is associated with increased mortality.
- mHLA-DR levels can serve as a valuable biomarker for identifying immune-paralysed states in pediatric sepsis.
- These findings highlight the potential of mHLA-DR as a prognostic tool in pediatric severe sepsis.
Objectives:
To assess the association between monocytic Human Leukocyte Antigen-DR (mHLA-DR) expression and outcome in children with severe sepsis.
Methods:
Consecutive children, aged 29 days to 15 years, who were admitted with severe sepsis or septic shock in the pediatric intensive care unit (PICU) were enrolled. mHLA-DR expression [antigen bound per cell (ABC)] was assessed on two time points: between 72 to 120 hours (P1) and 121 to 168 hours (P2), of stay in PICU and the difference between the two was calculated as delta mHLA-DR. Outcomes were noted for survival, mortality and secondary infection during the hospital stay.
Results:
Forty-seven children with median (IQR) age 24 (10, 96) months and a median (IQR) duration of illness of 3 (3, 5) days, were enrolled consecutively. Pediatric Logistic Organ Dysfunction (PELOD) score >10 was observed in 63.8% children. 18 children succumbed. The median mHLA-DR levels (ABC) at P1 were significantly higher in children who survived as compared with those who expired (7409 vs. 2509, P = 0.004). Similarly, the median mHLA-DR levels (ABC) at P2 were higher in those who survived than the expired group (14728 vs. 2085, P = 0.001). The median delta mHLA-DR levels (ABC) were 4574 and 309 for the survived and expired group, respectively (P = 0.012). mHLA-DR at P1 (P = 0.004), mHLA-DR at P2 (P = 0.001) and delta mHLA-DR (P = 0.012) was significantly associated with mortality but not associated with secondary infection. A negative correlation was observed between PELOD score and mHLA-DR at P1 (r = -0.25, P = 0.46), at P2 (r = -0.425, P = 0.018) and delta mHLA-DR (r = -0.27, P = 0.41). The area under curve (95%CI) of mHLA-DR expression (ABC) at P2 for a cutoff of < 6631 was 0.966 (0.907, 1.0) to predict mortality in severe sepsis.
Conclusions:
mHLA-DR levels were significantly lower in children who succumbed than those who survived at both time points. mHLA-DR levels can be a useful biomarker to diagnose immune-paralysed state.
