Competing interestsThe authors declare that they have no competing interests.Authors’ http://www.selleckchem.com/products/Erlotinib-Hydrochloride.html contributionsCG, FV, GM, and AL designed the study, collected clinical information, analyzed raw data, performed statistical analysis, and contributed to writing the paper. HK, FP, CM, and LD performed the immunological monitoring. AA, FG, and XH designed the study and contributed to writing the paper. AC and BA collected clinical information about trauma patients. All the authors read and approved the final version of the manuscript.AcknowledgementsWe would like to thank H��l��ne Thizy, Marion Provent, Carmen Fernandez, and Anne Portier for technical assistance and Nicolas Voirin for his fruitful advice on statistical analysis.

This research was supported by funds from the Hospices Civils de Lyon, by DHOS-Inserm ‘Recherche Clinique Translationnelle 2009′ (to GM and FG), by Fondation Innovation en Infectiologie (FINOVI) (to GM and FV), by the French Ministry of Health (PHRC 2008) (to GM and AL), and by US National Institutes of Health grants R01s GM46354 and GM53209 (to AA).
Severe sepsis is a common, expensive, and frequently fatal condition, leading to as many deaths annually as acute myocardial infarction [1]. Thus, a continuous search for new biomarkers in sepsis is necessary to aid early diagnosis and stratification of its severity.CD40 Ligand (CD40L) and its soluble counterpart (sCD40L) are proteins that exhibit prothrombotic and proinflammatory properties on binding to their cell surface receptor CD40 [2,3]. CD40L is a member of the tumour necrosis factor (TNF) family and is expressed as a transmembrane protein in activated platelets [4,5].

Cilengitide CD40L exerts several pro-inflammatory [6,7] and procoagulant [8-13] effects.Higher levels of sCD40L have been found in patients with acute coronary syndrome [14,15], stroke [16], systemic lupus erythematosus [17], and chronic lymphocytic leukemia [18]. The role of sCD40L in sepsis has hardly been studied. In some animal models, an increase in sCD40L was reported after the development of sepsis [19,20]. In humans, higher sCD40L levels were found in 49 patients with meningococcal sepsis and 15 patients with African tick bite fever compared with controls [21,22]. In other small series with pulmonary tuberculosis, higher sCD40L levels were found in patients with more severe disease [23,24]. A study including 35 septic patients found higher circulating sCD40L levels in non-surviving than in surviving patients [25]; however, there are no data on the association between circulating sCD40L levels and mortality of septic patients.We hypothesized that circulating sCD40L levels could be associated with an adverse outcome in patients with severe sepsis.