Occurrence of marked sepsis-induced immunosuppression in pediatric septic shock: a pilot study

Abstract

BackgroundWhile the process of sepsis-induced immunosuppression is now well described in adults, very little information is available on immune functions in pediatric sepsis. The current study investigated this in children with septic shock by performing immunomonitoring, including both innate (monocyte human leukocyte antigen-DR, mHLA-DR, expression) and adaptive immunity (lymphocyte subsets count), as well as cytokine concentrations (IL-6, IL-8, IL-10, IL-1Ra, TNF-α, IFN-γ). Subsequent objectives were to assess the associations between inflammatory response, potential immunosuppression and secondary acquired infection occurrence.MethodsSingle-center prospective observational study, including children aged between 1 month and 18 years admitted to pediatric intensive care unit (PICU) for septic shock. Age-matched controls were children hospitalized for elective surgery without any infectious criteria. Blood was sampled at day 1–2, 3–5, and 7–9 after sepsis onset. mHLA-DR and lymphocyte subsets count were measured by flow cytometry and cytokine concentrations by Luminex technology.ResultsA total of 26 children and 30 controls were included. Patients had lymphopenia, and mHLA-DR levels were significantly lower than controls at each time point (p < 0.0001). All cytokines peaked at day 1–2. Children with secondary acquired infection had lower day 3–5 mHLA-DR and higher pro-inflammatory cytokine concentrations (IL-6, IL-8 and TNF-α) at day 1–2 compared to children without secondary acquired infection.ConclusionsThe higher initial inflammatory cytokine production was, the more innate immunity was altered, while evaluated by low mHLA-DR expression. Children with decreased mHLA-DR expression developed more secondary acquired infections. Upon confirmation in multicenter cohorts, these results pave the way for immunostimulation for the most immunosuppressed children in order to prevent nosocomial infections in PICU.Trial registration PedIRIS study NCT02848144. Retrospectively registered 28 July 2016Electronic supplementary materialThe online version of this article (10.1186/s13613-018-0382-x) contains supplementary material, which is available to authorized users.

Massive increase in monocyte HLA-DR expression can be used to discriminate between septic shock and hemophagocytic lymphohistiocytosis-induced shock

“…We report here the case of a young woman with febrile shock which proved to be a HLH caused by drug-induced hypersensitivity syndrome (DIHS). As septic shock was initially suspected, the patient benefited from broad immunological screening during the first week of evolution [ 3 ]. Strikingly, this revealed massively increased expression of monocyte human leukocyte antigen-DR (mHLA-DR) at 137,021 ABC (antibody bound per cell), even though expected values in septic shock are usually drastically decreased [ 3 ].…”

“…As septic shock was initially suspected, the patient benefited from broad immunological screening during the first week of evolution [ 3 ]. Strikingly, this revealed massively increased expression of monocyte human leukocyte antigen-DR (mHLA-DR) at 137,021 ABC (antibody bound per cell), even though expected values in septic shock are usually drastically decreased [ 3 ]. In addition, a positive response to increasing doses of corticosteroids was observed over time (Fig.…”

Early immunosuppression was associated with poor prognosis in elderly patients with sepsis: secondary analysis of the ETASS study

“…Immunosuppression was associated with increased mortality and secondary infection, prolonged length of ICU stay and aggravated organ dysfunction in adult and children with sepsis [18,19,25,26].…”

Comment on: CD163 as a valuable diagnostic and prognostic biomarker of sepsis‐associated hemophagocytic lymphohistiocytosis in critically ill children. A call for HLA‐DR in HLH

“…To illustrate this aspect, we put here in perspective mHLA‐DR values obtained in 278 adult septic shock patients on ICU admission (from Gustave et al and ongoing study: #NCT02803346). As depicted in Figure , results in septic patients are extremely homogenous and show a nearly constant fall of mHLA‐DR (mHLA‐DR normal values in adult and pediatric healthy donors: 20 000‐40 000 antibody bound per cell (AB/C) . Less than 1 % mHLA‐DR values were comprised between 40 000 and 70 000 AB/C, while mHLA‐DR measurement performed in the HLH patient was at 138 000 AB/C 2 , reflecting tremendous monocyte activation consistent with HLH pathophysiology.…”

“…mHLA‐DR values are expressed as AB/C (antibody bound per cell). Hemophagocytic lymphohistiocytosis (HLH) arrow depicts a value observed for a HLH patient at the time of admission…”