the work of wu and colleagues   is in accordance with the recent concept of sepsis - induced immunosuppression . there is now agreement that many severe septic patients survive the first critical hours of the syndrome but eventually die later in a state of immunosuppression that is illustrated by patients ' difficulty to fight the primary bacterial infection , decreased resistance to secondary nosocomial infections and reactivation of viral infections normally solely pathogenic in the immunocompromised host . consequently , immunostimulatory therapies might be used to restore immune functions in the most immunodepressed patients . in the absence of any specific clinical signs of immune failure , however , it is beforehand critical to determine the best biological tools ( markers of septic patients ' immune failure ) enabling patient stratification . the most frequently assessed biomarker in the field to date is undeniably the measurement of hla - dr expression on circulating monocytes ( mhla - dr ) . there appears to be general consensus that diminished mhla - dr is a reliable marker for the development of immunosuppression in critically ill patients . indeed , decreased expression of this marker is regularly reported to be associated with higher mortality / risk for nosocomial infections in critically ill patients . more than 100 articles on this topic have been published in different icu conditions , including sepsis , trauma , burns , and stroke . it is becoming increasingly clear that the critical point after injury is the recovery of normal mhla - dr . schematically , mhla - dr rapidly returns to normal values ( generally in less than 1 week ) in injured patients with uneventful recovery , whereas this parameter remains constantly decreased in patients with adverse outcome/ secondary septic complications . in line with this hypothesis , wu and colleagues showed that low mhla - dr was associated with increased mortality in severe sepsis . most importantly , the authors propose that , more than a single value at a given time point , the dynamic change of mhla - dr over time would be a better predictor of mortality . indeed , in their study , single measurements of mhla - dr within the first week after patient admission ( either days 0 , 3 or 7 ) had no predictive value regarding mortality . in contrast , results expressed as dynamic parameters ( that is , between two time points ) provide excellent predictive values , especially calculated between days 0 and 3 or between days 0 and 7 ( areas under the curve of 0.92 and 0.94 , respectively , in receiver operating characteristic analysis ) . most importantly , after multivariate analysis , the authors show that these two parameters remain the sole independent predictors of mortality with an elevated significant odds ratio . overall , the present results confirm the concept that patients who do not start to restore normal immune functions are those who are going to die . these results are in agreement with two recent studies in which a weak slope of mhla - dr recovery was associated with increased risk of secondary infections in a mixed icu population   and in trauma . this outcome could have important consequences in patient management , by potentially allowing for the administration of tailored therapies aimed at restoring immune functions based on dynamic changes of immunological parameters . first , the study is monocentric in a small cohort of surgical patients ( that is , not necessarily representative of the whole septic population ) that present with relatively elevated mhla - dr values ( > 50% ) in comparison with results from the literature ( usually below 50% in severe septic patients ) . this moderate severity and the lack of statistical power due to the small size of the cohort may explain surprising results after multivariate analysis ( sequential organ failure assessment and acute physiology and chronic health evaluation ii scores were not significantly different between survivors and nonsurvivors , odds ratio with very large confidence intervals ) . indeed , the standardized recommended method for expressing mhla - dr results is as numbers of antibodies bound per cell and not as the percentage of positive cells . as an example , the authors suggest that a difference of 4.8% in mhla - dr between days 0 and 3 is of significance . although most probably correct from a statistical perspective , this threshold is hardly applicable in routine / technical practice because such a small percentage difference could be due to measurement variability by flow cytometry . overall and beyond these limitations , appropriately acknowledged by the authors , this study confirms that after injury ( for example , severe sepsis ) survivors tend to progressively normalize mhla - dr , contrary to non - survivors . this biologic parameter could thus provide critical information when assessed as a dynamic variable over time . this potential aspect now deserves to be validated in multicentric clinical studies using standardized flow cytometry protocols .
increasing evidence suggests that the secondary phase of sepsis ( that is , after the first proinflammatory hours ) is characterized by the occurrence of a systemic failure of the immune system . in the most immunodepressed patients 
 , therapies could be used to restore normal immune functions . however 
 , biomarkers need to be developed to beforehand specifically identify these patients . of these biomarkers , 
 diminished monocyte hla - dr expression has rapidly become the most popular . 
 herein , novel perspectives regarding monocyte hla - dr assessed as a dynamic parameter in septic patients will be discussed in the context of a recently published study investigating daily evolution of monocyte hla - dr with regard to 28 day - mortality after severe sepsis .