Related Experiment Video
Updated: Oct 14, 2025

Separation of Immune Cell Subpopulations in Peripheral Blood Samples from Children with Infectious Mononucleosis
Published on: September 7, 2022
Association of monocyte HLA-DR expression over time with secondary infection in critically ill children: a
Nienke N Hagedoorn1, Pinar Kolukirik2, Nicole M A Nagtzaam3
1Department of General Pediatrics, Erasmus MC Sophia, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Abstract:
An impaired immune response could play a role in the acquisition of secondary infections in critically ill children. Human leukocyte antigen-DR expression on monocytes (mHLA-DR) has been proposed as marker to detect immunosuppression, but its potential to predict secondary infections in critically ill children is unclear. We aimed to assess the association between mHLA-DR expression at several timepoints and the change of mHLA-DR expression over time with the acquisition of secondary infections in critically ill children. In this prospective observational study, children < 18 years with fever and/or suspected infection (community-acquired or hospital-acquired) were included at a paediatric intensive care unit in the Netherlands. mHLA-DR expression was determined by flow cytometry on day 1, day 2-3 and day 4-7. The association between delta-mHLA-DR expression (difference between last and first measurement) and secondary infection was assessed by multivariable regression analysis, adjusted for age and Paediatric Logistic Organ Dysfunction-2 score. We included 104 patients at the PICU (median age 1.2 years [IQR 0.3-4.2]), of whom 28 patients (27%) developed a secondary infection. Compared to 93 healthy controls, mHLA-DR expression of critically ill children was significantly lower at all timepoints. mHLA-DR expression did not differ at any of the time points between patients with and without secondary infection. In addition, delta-mHLA-DR expression was not associated with secondary infection (aOR 1.00 [95% CI 0.96-1.04]).Conclusions: Our results confirm that infectious critically ill children have significantly lower mHLA-DR expression than controls. mHLA-DR expression was not associated with the acquisition of secondary infections. What is Known: • An impaired immune response, estimated by mHLA-DR expression, could play an essential role in the acquisition of secondary infections in critically ill children. • In critically ill children, large studies on the association of mHLA-DR expression with secondary infections are scarce. What is New: • Our study confirms that critically ill children have lower mHLA-DR expression than healthy controls. • mHLA-DR expression and change in mHLA-DR was not associated with the acquisition of secondary infection.
Insights
Critically ill children show lower monocyte human leukocyte antigen-DR (mHLA-DR) expression than healthy controls. However, mHLA-DR levels and their changes do not predict secondary infections in these vulnerable patients.
Area of Science:
- Immunology
- Critical Care Medicine
- Pediatrics
Background:
- Impaired immune responses may increase secondary infection risk in critically ill children.
- Monocyte human leukocyte antigen-DR (mHLA-DR) expression is a proposed marker for immunosuppression.
- The predictive value of mHLA-DR for secondary infections in pediatric critical care is not well-established.
Purpose of the Study:
- To investigate the association between mHLA-DR expression and the development of secondary infections in critically ill children.
- To assess if changes in mHLA-DR expression over time correlate with secondary infection acquisition.
Main Methods:
- Prospective observational study in a pediatric intensive care unit (PICU).
- Measured mHLA-DR expression via flow cytometry on days 1, 2-3, and 4-7 in children <18 years.
- Analyzed the association between mHLA-DR expression, delta-mHLA-DR, and secondary infections using multivariable regression.
Main Results:
- Critically ill children exhibited significantly lower mHLA-DR expression compared to healthy controls at all time points.
- No significant difference in mHLA-DR expression was observed between patients with and without secondary infections.
- Delta-mHLA-DR expression was not associated with the acquisition of secondary infections.
Conclusions:
- Critically ill children have demonstrably lower mHLA-DR expression than healthy individuals.
- mHLA-DR expression levels and their dynamics do not serve as predictors for secondary infections in this population.

