Association between serum soluble CD40 ligand levels and mortality in patients with severe sepsis
1 Intensive Care Unit, Hospital Universitario de Canarias, Ofra, s/n, La Laguna - 38320, Santa Cruz de Tenerife, Spain
2 Intensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Crta del Rosario s/n, Santa Cruz de Tenerife - 38010, Spain
3 Biochemistry Deparment, Clínica Universidad de Navarra, Avda Pío XII n°55, Pamplona - 31008, Spain
4 Laboratory Deparment, Hospital Universitario de Canarias, Ofra, s/n, La Laguna - 38320, Santa Cruz de Tenerife, Spain
5 Intensive Care Unit, Hospital Universitario Dr. Negrín, Barranco de la Ballena s/n, Las Palmas de Gran Canaria - 35010, Spain
6 Intensive Care Unit, Hospital Clínico Universitario de Valencia, Avda. Blasco Ibáñez no. 17-19, Valencia - 46004, Spain
7 Intensive Care Unit, Hospital San Jorge de Huesca, Avenida Martínez de Velasco n°36, Huesca - 22004, Spain
8 Intensive Care Unit, Hospital Insular, Plaza Dr. Pasteur s/n, Las Palmas de Gran Canaria - 35016, Spain
9 Mixed Research Unit HUC-ULL, Hospital Universitario de Canarias, Ofra, s/n, La Laguna - 38320, Santa Cruz de Tenerife, Spain
10 Atherosclerosis Research Laboratory, CIMA-University of Navarra, Avda Pío XII no. 55, Pamplona - 31008, Spain
11 Laboratory Department, Hospital San Jorge de Huesca, Avenida Martínez de Velasco no. 36, Huesca - 22004, Spain
Critical Care 2011, 15:R97 doi:10.1186/cc10104
See related letter by Tuinman and Juffermans, http://ccforum.com/content/15/3/429, and related letter by Chew and Thorlacius, http://ccforum.com/content/15/4/438Published: 15 March 2011
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.
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.
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).
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.