Human leukocyte antigen DR (HLA-DR) represents the capacity of monocytes for antigen presentation and crosstalk to T helper cells, enabling the activation of the adaptive immune system. HLA-DR on monocytes is considered a surrogate marker of sepsis-induced immunosuppression. Survivors show a significant increase in the percentage of HLA-DR-positive monocytes during the course of sepsis [
5]. Using flow cytometry in a cohort of patients with severe sepsis, Wu et al. demonstrated that an increment of 4.8% at day 3 following admission to the ICU yielded a NPV of 98% to rule out mortality at 28 days, while an increment of 9% at day 7 yielded an NPV of 97.2% [
6]. Landelle et al. also employed flow cytometry and demonstrated that monocyte HLA-DR expressed as the means of fluorescence intensity (MFI) is useful to rule out nosocomial infections after septic shock. Exhibiting > 54 MFIs by days 3–4 following admission to the ICU showed an NPV of 86% to exclude nosocomial infections in these patients [
7]. Another promising biological marker to rule out complicated outcomes in sepsis patients during hospitalization in the ICU is interleukin-7 receptor (IL-7R). Interleukin 7 is primarily a survival factor for different subpopulations of lymphoid cells. Using reverse transcription quantitative polymerase chain reaction in whole blood, Delwarde et al. found a gene expression value for IL-7R at day 3 following septic shock diagnosis that yielded a high NPV for 28-day mortality (86%) [
8]. This value corresponded to a ratio of 0.20 between the expression of IL-7R and hypoxanthine phosphoribosyltransferase 1 as a reference gene. Immunoglobulin M levels in serum could also help to identify patients with better outcomes. The work of Giamarellos-Bourboulis EJ et al. supported that the kinetics of immunoglobulin M levels in sepsis patients over time could help to rule out progression to septic shock and mortality [
9]. Using advanced informatic techniques, Sweeney et al. evidenced the existence in sepsis of a gene expression signature of adaptive immune activation associated with a lower clinical severity and lower mortality [
10]. Similarly, Davenport et al. identified a sepsis response signature 1 (SRS1) characterizing individuals with an immunosuppressed phenotype that included features of endotoxin tolerance, T cell exhaustion, and the downregulation of human leucocyte antigen class II, which was associated with higher 14-day mortality [
11]. The persistence/presence of the “adaptive” signature or the correction/absence of the SRS1 signature during sepsis could potentially help to identify patients at low risk of developing complications.