title: Circulating immature granulocytes with T-cell killing functions predict sepsis deterioration*.
abstract: OBJECTIVE
  Primary objective was to identify leukocyte subsets that could predict the early evolution of sepsis at 48 hours (i.e., deterioration or stability/improvement). Secondary objectives were to evaluate the prognostic value of leukocyte subsets on mortality and immunosuppressive properties of immature granulocytes.
  
  
  METHODS
  Twenty-three peripheral blood leukocyte subsets were analyzed using a new-generation 10-color flow cytometry. T-cell killing activity of immature granulocytes was explored using a sorting method specifically developed.
  
  
  METHODS
  ICUs and emergency departments.
  
  
  METHODS
  All patients admitted to emergency department and ICU for sepsis ongoing for less than 24 hours were eligible. Exclusion criteria were pregnancy, age less than 18 years, solid tumors, HIV infection, hematological or inflammatory conditions, and immunosuppressive drugs. Finally, 177 patients were included.
  
  
  METHODS
  None.
  
  
  RESULTS
  The two most salient features of sepsis were decreased CD10 (CD10) and CD16 (CD16) expressions on granulocytes. With a threshold of 90% of CD10 and 15% of CD16 granulocytes, these immunophenotypic features, which are those of immature granulocytes, predicted sepsis deterioration at 48 hours with a sensitivity of 57% and 70% and a specificity of 78% and 82%, respectively. Survival rate at day 30 was 99% for patients without CD10 and CD16, 85% for patients with increased CD16 only, and 63% for patients with increased CD16 and CD10 granulocytes (p < 0.001). Among CD16 immature granulocytes, we identified a CD14/CD24 myeloid-derived suppressor cell subset with the capability of killing activated T cells. Consistently, an excess of CD16 immature granulocytes was associated with both CD3 and CD4 T-cell lymphopenia in deteriorating patients.
  
  
  CONCLUSIONS
  Circulating immature granulocytes predicted early sepsis deterioration and were enriched in myeloid-derived suppressor cells which could be responsible for immunosuppression through the induction of T-cell lymphopenia.
authors.affiliation: 1Hematology Laboratory, Dupuytren University Hospital, Limoges, France. 2Intensive Care Unit, Dupuytren University Hospital, Limoges, France. 3Inserm UMR1009, Paris-Sud University, Gustave Roussy Institute, Villejuif, France. 4Inserm CIC-P 0202, Tours Regional University Hospital, François Rabelais, University, Tours, France. 5Intensive Care Unit, Central Hospital, Nancy, France. 6Immunology Laboratory, Brabois University Hospital, Nancy, France. 7Hematology Laboratory, Haut-Lévêque University Hospital, Pessac, France. 8Inserm CIC-P 0801, Dupuytren University Hospital, Limoges, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Guérin
authors.forename: Marie
authors.initials: M
authors.lastname: Orabona
authors.forename: Marie-Astrid
authors.initials: MA
authors.lastname: Raquil
authors.forename: Bruno
authors.initials: B
authors.lastname: Giraudeau
authors.forename: Rémy
authors.initials: R
authors.lastname: Bellier
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gibot
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Béné
authors.forename: Francis
authors.initials: F
authors.lastname: Lacombe
authors.forename: Nathalie
authors.initials: N
authors.lastname: Droin
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: Philippe
authors.initials: P
authors.lastname: Vignon
authors.forename: Jean
authors.initials: J
authors.lastname: Feuillard
authors.forename: Bruno
authors.initials: B
authors.lastname: François
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D005260:Female; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018805:Sepsis / Q000097:blood / Q000276:immunology* / Q000401:mortality*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015415:Biomarkers