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.
Highlights
Ill patients are at risk for a prolonged period of immunosuppression, potentially leading to an increased risk of secondary infections [1,2,3,4]
Our results confirm that infectious critically ill children have significantly lower Monocytic human leukocyte antigen-DR (mHLA-DR) expression than controls. mHLA-DR expression was not associated with the acquisition of secondary infections
Our study confirms that critically ill children have lower mHLA-DR expression than healthy controls
Summary
Ill patients are at risk for a prolonged period of immunosuppression, potentially leading to an increased risk of secondary infections [1,2,3,4]. Monocytic human leukocyte antigen-DR (mHLA-DR) expression has been shown a reliable biomarker in critically ill patients to estimate immunosuppression. A prolonged decrease in mHLA-DR expression has been associated with acquisition of secondary infection and mortality in small studies [13, 19, 20, 23, 24] one study did not found an association [25]. The largest study to date included > 400 adult patients and found lower mHLA-DR values in non-survivors. The authors concluded that mHLA-DR expression was not suitable as predictive parameter due to limited discriminative ability [26]
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