title: Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock.
abstract: 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.
  
  
  METHODS
  Prospective observational study performed in two adult intensive care units at a university hospital.
  
  
  METHODS
  93 consecutive patients with septic shock.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Immunology Laboratory, Hôpital Neurologique, Lyon, France. guillaume.monneret@chu-lyon.fr
authors.forename: Guillaume
authors.initials: G
authors.lastname: Monneret
authors.forename: Alain
authors.initials: A
authors.lastname: Lepape
authors.forename: Nicolas
authors.initials: N
authors.lastname: Voirin
authors.forename: Julien
authors.initials: J
authors.lastname: Bohé
authors.forename: Fabienne
authors.initials: F
authors.lastname: Venet
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Debard
authors.forename: Hélène
authors.initials: H
authors.lastname: Thizy
authors.forename: Jacques
authors.initials: J
authors.lastname: Bienvenu
authors.forename: François
authors.initials: F
authors.lastname: Gueyffier
authors.forename: Philippe
authors.initials: P
authors.lastname: Vanhems
mesh_terms: D000368:Aged; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D011379:Prognosis; D011446:Prospective Studies; D012772:Shock, Septic / Q000276:immunology* / Q000401:mortality*; D015996:Survival Rate
chemical_list: D006684:HLA-DR Antigens