Concomitant Assessment of Monocyte HLA-DR Expression and Ex Vivo TNF-α Release as Markers of Adverse Outcome after Various Injuries-Insights from the REALISM Study.

Frank Bidar,Karen Brengel-Pesce,On Behalf Of The Realism Study Group ,Laurence Quemeneur,Lionel K Tan,Thomas Rimmelé,Fabienne Venet,Philippe Leissner,Filippo Conti,Anne-Claire Lukaszewicz,Julien Textoris,Guillaume Monneret,Maxime Bodinier

doi:10.3390/jcm11010096

Abstract

Intensive care unit (ICU) patients develop an altered host immune response after severe injuries. This response may evolve towards a state of persistent immunosuppression that is associated with adverse clinical outcomes. The expression of human leukocyte antigen DR on circulating monocytes (mHLA-DR) and ex vivo release of tumor necrosis factor α (TNF-α) by lipopolysaccharide-stimulated whole blood are two related biomarkers offered to characterize this phenomenon. The purpose of this study was to concomitantly evaluate the association between mHLA-DR and TNF-α release and adverse clinical outcome (i.e., death or secondary infection) after severe trauma, sepsis or surgery in a cohort of 353 ICU patients. mHLA-DR and TNF-α release was similarly and significantly reduced in patients whatever the type of injury. Persistent decreases in both markers at days 5–7 (post-admission) were significantly associated with adverse outcomes. Overall, mHLA-DR (measured by flow cytometry) appears to be a more robust and standardized parameter. Each marker can be used individually as a surrogate of immunosuppression, depending on center facilities. Combining these two parameters could be of interest to identify the most immunosuppressed patients presenting with a high risk of worsening. This last aspect deserves further exploration.

Highlights

The third sepsis conference in 2016 established a new definition for sepsis, which is depicted as a life-threatening organ dysfunction caused by a dysregulated host response to infection [1]
Marked immunosuppression has been partially described in patients admitted to the intensive care unit (ICU) for severe trauma and major surgery [7,8]
Because the immune response during the Intensive care unit (ICU) course can vary among patients and over time, it is necessary to correctly identify the patients who will most benefit from these treatments [11]

Summary

Introduction

The third sepsis conference in 2016 established a new definition for sepsis, which is depicted as a life-threatening organ dysfunction caused by a dysregulated host response to infection [1]. This reflects our evolving understanding of sepsis pathophysiology since the host immune response in sepsis is complex, rapidly evolving over time and involves an initial excessive inflammation associated with a compensatory anti-inflammatory 4.0/). Given improvements in early sepsis detection and acute intensive care management, most patients survive their initial septic insult, but a significant number do not fully recover immune functions and experience recurrent infections, which may contribute to increased morbidity or mortality [5,6]. The development of reliable biomarkers to identify individuals with clinically meaningful immunosuppression is required [9,12]

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