Soluble CD40 ligand, a mediator of sepsis or of transfusion-related adverse effects?

Abstract

Dr Lorente and colleagues [1] report on the interesting association between serum soluble CD40 ligand (sCD40L) levels and mortality in patients with sepsis. Some variables that can influence outcome in sepsis were accounted for in their analysis. However, the amount of transfused blood products, which may influence levels of sCD40L, was not reported. sCD40L accumulates to biologically relevant levels during storage of blood products [2,3], in particular of platelet products. Following transfusion, blood products can induce an inflammatory reaction - by activating CD40-positive cells - associated with the occurrence of acute lung injury and other potential serious complications [3]. Levels of sCD40L were also found to be elevated in patients with lung injury following transfusion [2]. Even more, transfusion itself contributes to mortality in the critically ill [4], as well as to adverse outcome of sepsis [5]. Taken together, we suggest that blood transfusion could have potentially influenced both serum sCD40L levels and outcome in the study performed by Lorente and colleagues. The authors state that modulation of sCD40L levels could represent a therapeutic target. Would it not be more appropriate to question whether sCD40L from (stored) blood products contributed to elevated serum levels in their trial, before embarking on therapeutic interventions?