title: Association between serum soluble CD40 ligand levels and mortality in patients with severe sepsis.
abstract: BACKGROUND
  CD40 Ligand (CD40L) and its soluble counterpart (sCD40L) are proteins that exhibit prothrombotic and proinflammatory properties on binding to their cell surface receptor CD40. The results of small clinical studies suggest that sCD40L levels could play a role in sepsis; however, there are no data on the association between sCD40L levels and mortality of septic patients. Thus, the aim of this study was to determine whether circulating sCD40L levels could be a marker of adverse outcome in a large cohort of patients with severe sepsis.
  
  
  METHODS
  This was a multicenter, observational and prospective study carried out in six Spanish intensive care units. Serum levels of sCD40L, tumour necrosis factor-alpha and interleukin-10, and plasma levels of tissue factor were measured in 186 patients with severe sepsis at the time of diagnosis. Serum sCD40L was also measured in 50 age- and sex-matched controls. Survival at 30 days was used as the endpoint.
  
  
  RESULTS
  Circulating sCD40L levels were significantly higher in septic patients than in controls (P = 0.01), and in non-survivors (n = 62) compared to survivors (n = 124) (P = 0.04). However, the levels of CD40L were not different regarding sepsis severity. Logistic regression analysis showed that sCD40L levels >3.5 ng/mL were associated with higher mortality at 30 days (odds ratio = 2.89; 95% confidence interval = 1.37 to 6.07; P = 0.005). The area under the curve of sCD40L levels >3.5 ng/mL as predictor of mortality at 30 days was 0.58 (95% CI = 0.51 to 0.65; P = 0.03).
  
  
  CONCLUSIONS
  In conclusion, circulating sCD40L levels are increased in septic patients and are independently associated with mortality in these patients; thus, its modulation could represent an attractive therapeutic target.
authors.affiliation: Intensive Care Unit, Hospital Universitario de Canarias, Ofra, s/n, La Laguna - 38320, Santa Cruz de Tenerife, Spain. lorentemartin@msn.com
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lorente
authors.forename: María M
authors.initials: MM
authors.lastname: Martín
authors.forename: Nerea
authors.initials: N
authors.lastname: Varo
authors.forename: Juan María
authors.initials: JM
authors.lastname: Borreguero-León
authors.forename: Jordi
authors.initials: J
authors.lastname: Solé-Violán
authors.forename: José
authors.initials: J
authors.lastname: Blanquer
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Labarta
authors.forename: César
authors.initials: C
authors.lastname: Díaz
authors.forename: Alejandro
authors.initials: A
authors.lastname: Jiménez
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pastor
authors.forename: Felipe
authors.initials: F
authors.lastname: Belmonte
authors.forename: Josune
authors.initials: J
authors.lastname: Orbe
authors.forename: José A
authors.initials: JA
authors.lastname: Rodríguez
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gómez-Melini
authors.forename: José M
authors.initials: JM
authors.lastname: Ferrer-Agüero
authors.forename: José
authors.initials: J
authors.lastname: Ferreres
authors.forename: María C
authors.initials: MC
authors.lastname: Llimiñana
authors.forename: José A
authors.initials: JA
authors.lastname: Páramo
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000401:mortality*; D015996:Survival Rate / Q000639:trends
chemical_list: D015415:Biomarkers; D023201:CD40 Ligand