title: Lack of recovery in monocyte human leukocyte antigen-DR expression is independently associated with the development of sepsis after major trauma.
abstract: BACKGROUND
  Major trauma is characterized by an overwhelming pro-inflammatory response and an accompanying anti-inflammatory response that lead to a state of immunosuppression, as observed after septic shock. Diminished monocyte Human Leukocyte Antigen DR (mHLA-DR) is a reliable marker of monocyte dysfunction and immunosuppression. The main objective of this study was to determine the relation between mHLA-DR expression in severe trauma patients and the development of sepsis.
  
  
  METHODS
  We conducted a prospective observational study over 23 months in a trauma intensive care unit at a university hospital. Patients with an Injury Severity Score (ISS) over 25 and age over 18 were included. mHLA-DR was assessed by flow cytometry protocol according to standardized protocol. Mann-Whitney U-test for continuous non-parametric variables, independent paired t test for continuous parametric variables and chi-square test for categorical data were used.
  
  
  RESULTS
  mHLA-DR was measured three times a week during the first 14 days. One hundred five consecutive severely injured patients were monitored (ISS 38 ± 17, SAPS II 37 ± 16). Thirty-seven patients (35%) developed sepsis over the 14 days post-trauma. At days 1-2, mHLA-DR was diminished in the whole patient population, with no difference with the development of sepsis. At days 3-4, a highly significant difference appeared between septic and non-septic patients. Non- septic patients showed an increase in mHLA-DR levels, whereas septic patients did not (13,723 ± 7,766 versus 9,271 ± 6,029 antibodies per cell, p = .004). Most importantly, multivariate logistic regression analysis, after adjustment for usual clinical confounders (adjusted OR 5.41, 95% CI 1.42-20.52), revealed that a slope of mHLA-DR expression between days1-2 and days 3-4 below 1.2 remained associated with the development of sepsis.
  
  
  CONCLUSIONS
  Major trauma induced an immunosuppression, characterized by a decrease in mHLA-DR expression. Importantly, after multivariate regression logistic analysis, persistent decreased expression was assessed to be in relation with the development of sepsis. This is the first study in trauma patients showing a link between the lack of immune recovery and the development of sepsis on the basis of the standardized protocol. Monitoring immune function by mHLA-DR measurement could be useful to identify trauma patients at a high risk of infection.
authors.affiliation: Hospices Civils de Lyon, Service de réanimation, Hôpital Edouard Herriot, 5 place d'Arsonval-69437 Lyon Cedex 03, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cheron
authors.forename: Bernard
authors.initials: B
authors.lastname: Floccard
authors.forename: Bernard
authors.initials: B
authors.lastname: Allaouchiche
authors.forename: Caroline
authors.initials: C
authors.lastname: Guignant
authors.forename: Françoise
authors.initials: F
authors.lastname: Poitevin
authors.forename: Christophe
authors.initials: C
authors.lastname: Malcus
authors.forename: Jullien
authors.initials: J
authors.lastname: Crozon
authors.forename: Alexandre
authors.initials: A
authors.lastname: Faure
authors.forename: Christian
authors.initials: C
authors.lastname: Guillaume
authors.forename: Guillaume
authors.initials: G
authors.lastname: Marcotte
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vulliez
authors.forename: Olivier
authors.initials: O
authors.lastname: Monneuse
authors.forename: Guillaume
authors.initials: G
authors.lastname: Monneret
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006684:HLA-DR Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D011446:Prospective Studies; D020127:Recovery of Function / Q000276:immunology; D018805:Sepsis / Q000209:etiology / Q000276:immunology* / Q000378:metabolism*; D014947:Wounds and Injuries / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D006684:HLA-DR Antigens