title: Decreased T-cell repertoire diversity in sepsis: a preliminary study.
abstract: OBJECTIVE
  Septic syndromes are the leading causes of mortality in intensive care units. In patients, the occurrence of sepsis-induced immune suppression is associated with delayed mortality, although the exact role of lymphocyte dysfunctions is not well established. The objective of this study was to investigate T-cell receptor diversity, an important feature of T-cell response, in patients with septic shock.
  
  
  METHODS
  Preliminary prospective observational study.
  
  
  METHODS
  Adult intensive care units in a university hospital.
  
  
  METHODS
  Patients with septic shock (n = 41) sampled twice after the onset of shock (early after inclusion [day 1] and at the end of the first week [day 7]).
  
  
  RESULTS
  Using a novel molecular biology technique, the combinatorial diversity of human T-cell receptor β-chain (TRB locus) was measured in peripheral blood. Patients with septic shock presented with a marked decreased T-cell receptor diversity after the onset of shock in comparison with normal values. Importantly, in paired samples, a very steep recovery slope of T-cell receptor diversity, never described in other clinical situations, was observed between day 1 and day 7 (p < 0.0001, Wilcoxon's paired test). Decreased T-cell receptor diversity was associated with mortality (log-rank test, p = 0.0058; hazard ratio = 4.48; 95% confidence interval 1.96-53.32), and the development of nosocomial infections (p < 0.05, Mann-Whitney U test).
  
  
  CONCLUSIONS
  Our results show for the first time that septic patients present with a marked decreased T-cell receptor diversity that returned rapidly toward normal values over time. This opens novel cognitive research perspectives that deserve to be investigated in experimental models of sepsis. After confirmation in larger cohorts of these preliminary results, T-cell receptor diversity measurements may become a crucial tool to monitor immune functions in ICU patients.
authors.affiliation: Cellular Immunology Laboratory, Hôpital E Herriot, Lyon, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Venet
authors.forename: Orchidée
authors.initials: O
authors.lastname: Filipe-Santos
authors.forename: Alain
authors.initials: A
authors.lastname: Lepape
authors.forename: Christophe
authors.initials: C
authors.lastname: Malcus
authors.forename: Françoise
authors.initials: F
authors.lastname: Poitevin-Later
authors.forename: Audrey
authors.initials: A
authors.lastname: Grives
authors.forename: Nadia
authors.initials: N
authors.lastname: Plantier
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pasqual
authors.forename: Guillaume
authors.initials: G
authors.lastname: Monneret
mesh_terms: D000328:Adult; D000368:Aged; D003428:Cross Infection / Q000453:epidemiology / Q000276:immunology; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology*; D014644:Genetic Variation / Q000276:immunology*; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values; D012772:Shock, Septic / Q000276:immunology* / Q000401:mortality; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta