title: Decreased HLA-DR antigen-associated invariant chain (CD74) mRNA expression predicts mortality after septic shock.
abstract: BACKGROUND
  Septic syndromes remain the leading cause of mortality in intensive care units (ICU). Septic patients rapidly develop immune dysfunctions, the intensity and duration of which have been linked with deleterious outcomes. Decreased mRNA expressions of major histocompatibility complex (MHC) class II-related genes have been reported after sepsis. We investigated whether their mRNA levels in whole blood could predict mortality in septic shock patients.
  
  
  METHODS
  A total of 93 septic shock patients were included. On the third day after shock, the mRNA expressions of five MHC class II-related genes (CD74, HLA-DRA, HLA-DMB, HLA-DMA, CIITA) were measured by qRT-PCR and monocyte human leukocyte antigen-DR (mHLA-DR) by flow cytometry.
  
  
  RESULTS
  A significant correlation was found among MHC class II related gene expressions. Among mRNA markers, the best prognostic value was obtained for CD74 (HLA-DR antigen-associated invariant chain). For this parameter, the area under the receiver operating characteristic curve (AUC) was calculated (AUC = 0.67, 95% confidence interval (CI) = 0.55 to 0.79; P = 0.01) as well as the optimal cut-off value. After stratification based on this threshold, survival curves showed that a decreased CD74 mRNA level was associated with increased mortality after septic shock (Log rank test, P = 0.0043, Hazard Ratio = 3.0, 95% CI: 1.4 to 6.5). Importantly, this association remained significant after multivariate logistic regression analysis including usual clinical confounders (that is, severity scores, P = 0.026, Odds Ratio = 3.4, 95% CI: 1.2 to 9.8).
  
  
  CONCLUSIONS
  Decreased CD74 mRNA expression significantly predicts 28-day mortality after septic shock. After validation in a larger multicentric study, this biomarker could become a robust predictor of death in septic patients.
authors: Marie-Angélique
authors: MA
authors: Cazalis
authors: Arnaud
authors: A
authors: Friggeri
authors: Laura
authors: L
authors: Cavé
authors: Julie
authors: J
authors: Demaret
authors: Véronique
authors: V
authors: Barbalat
authors: Elisabeth
authors: E
authors: Cerrato
authors: Alain
authors: A
authors: Lepape
authors: Alexandre
authors: A
authors: Pachot
authors: Guillaume
authors: G
authors: Monneret
authors: Fabienne
authors: F
authors: Venet
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood*; D000949:Histocompatibility Antigens Class II / Q000097:blood*; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000097:blood; D012772:Shock, Septic / Q000097:blood* / Q000401:mortality*
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D015415:Biomarkers; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; C045084:invariant chain