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Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock.
Monneret, Guillaume 1,6; Lepape, Alain 3; Voirin, Nicolas 4; Bohe, Julien 3; Venet, Fabienne 1; Debard, Anne-Lise 2; Thizy, Helene 5; Bienvenu, Jacques 2; Gueyffier, Francois 5; Vanhems, Philippe 4
[Article] Intensive Care Medicine. 32(8):1175-1183, August 2006.

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Objective: The immediate overwhelming release of inflammatory mediators in septic shock is rapidly followed by strong anti-inflammatory responses inducing a state of immunosuppression. The patients who survive the initial hyper-inflammatory step of septic shock but subsequently die may be those who do not recover from immunosuppression. We assessed whether a low monocyte human leukocyte antigen-DR (mHLA-DR) expression, proposed as a marker of immunosuppression, is an independent predictor of mortality in patients who survived the initial 48 h of septic shock.

Design and setting: Prospective observational study performed in two adult intensive care units at a university hospital.

Patients: 93 consecutive patients with septic shock.

Measurements and results: At days 1-2, mHLA-DR values (determined by flow cytometry) were not significantly different between survivors and non-survivors. A sharp difference became highly significant at days 3-4 when survivors had increased their values, while non-survivors had not (43% vs. 18%, percentage of HLA-DR positive monocyte, p < 0.001). Multivariate logistic regression analysis revealed that low mHLA-DR (< 30%) at days 3-4 remained independently associated with mortality after adjustment for usual clinical confounders, adjusted odds ratio (CI): 6.48 (95% CI: 1.62-25.93).

Conclusion: The present preliminary results show that mHLA-DR is an independent predictor of mortality in septic shock patients. Being a marker of immune failure, low mHLA-DR may provide a rationale for initiating therapy to reverse immunosuppression. After validation of the current results in multicenter studies, mHLA-DR may help to stratify patients when designing a mediator-directed therapy in a time-dependent manner.