title: Soluble human leukocyte antigen-G5 in septic shock: marked and persisting elevation as a predictor of survival.
abstract: OBJECTIVE
  Although it is established that septic shock induces immunosuppression, the mechanisms for this phenomenon remain poorly understood. Human leukocyte antigen-G exerts strong inhibitory effects that are directed at different arms of the immune system. The main objective of the current study was to measure human leukocyte antigen-G (soluble and membrane proteins) in septic shock.
  
  
  METHODS
  Observational study.
  
  
  METHODS
  Adult intensive care units in a university hospital.
  
  
  METHODS
  Sixty-four consecutive patients with septic shock (7 days of follow-up).
  
  
  METHODS
  None.
  
  
  RESULTS
  We measured plasma human leukocyte antigen-G5 (with enzyme linked immunosorbent assay) and human leukocyte antigen-G1 (with flow cytometry) expression on circulating leukocytes. As early as days 1-2 after the onset of shock, we observed a marked elevation of soluble human leukocyte antigen-G5 in patients: 60 ng/mL (34-146) as median (Q1-Q3) (reference values <5 ng/mL). This increase was stable over time. Most important, we also found at days 1-2 a significant difference between survivors and nonsurvivors: 109 ng/mL (43-183) vs. 37 ng/mL (19-61), respectively (p = .003). This difference remained significant until day 7. Receiver operating characteristic curve analysis showed that human leukocyte antigen-G5 was a good predictor of outcome (areas under curves: 0.76 and 0.84 at days 1-2 and days 3-4, respectively, p < .001). Adjusted logistic regression analysis suggested that human leukocyte antigen-G5 at days 3-5 was a better prognostic marker than decreased monocyte human leukocyte antigen-DR and/or severity score.
  
  
  CONCLUSIONS
  The present results show a marked elevation of soluble human leukocyte antigen-G5 protein during septic shock. We may hypothesize that given its potent inhibitory properties and its association with survival, human leukocyte antigen-G5 has an important role in the numerous negative feedback signals that limit the process of inflammation during septic shock.
authors.affiliation: Hospices Civils de Lyon, Hôpital Neurologique, Laboratoire d'Immunologie, Lyon, France. guillaume.monneret@chu-lyon.fr
authors.forename: Guillaume
authors.initials: G
authors.lastname: Monneret
authors.forename: Nicolas
authors.initials: N
authors.lastname: Voirin
authors.forename: Irène
authors.initials: I
authors.lastname: Krawice-Radanne
authors.forename: Julien
authors.initials: J
authors.lastname: Bohé
authors.forename: Alain
authors.initials: A
authors.lastname: Lepape
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rouas-Freiss
authors.forename: Edgardo D
authors.initials: ED
authors.lastname: Carosella
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D005260:Female; D006680:HLA Antigens / Q000097:blood / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000378:metabolism*; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology; D016015:Logistic Models; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012772:Shock, Septic / Q000276:immunology*; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D006684:HLA-DR Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I