Immune-reactive soluble OX40 ligand, soluble CD40 ligand, and interleukin-27 are simultaneously oversecreted in platelet components associated with acute transfusion reactions


  • This work was supported by grants from the French National Blood Service–EFS (Grant APR), France; the Association for Research in Transfusion (ART), Paris, France; the Agence Nationale de la Sécurité et du Médicament et des produits de santé (ANSM–AAP-2012-011, Reference 2012S055); and the Association “Les Amis de Rémi,” Savigneux, France.
  • HHC and FC designed and performed the study, analyzed the data, and wrote the paper; KAN, PD, CAA, MAE, PC, BP, and LA analyzed the data; JCO produced and analyzed the data; and OG coordinated the study, cowrote the manuscript, and supervised the entire project.



Leukoreduction of labile blood components dramatically decreases the frequency of minor, intermediate, and severe adverse events (AEs), referred to as acute transfusion reactions (ATRs), especially after transfusion of platelet components (PCs). The pathophysiology of AEs may result from accumulation of soluble, secreted, platelet (PLT) factors with proinflammatory functions stored in PCs. Thus, several cosynergizing factors associated with PLT accumulation in PCs may contribute to clinically reported ATRs with inflammatory symptoms.

Study Design and Methods

We screened for 65 PLT-associated secretory products in PCs that caused ATRs and identified PLT molecules associated with ATRs and inflammation. A functional in vitro study using PC supernatants assayed on reporting immune cells was performed to indicate relevance.


Among 10,600 apheresis PCs, 30 caused inflammatory ATRs and contained significantly elevated levels of soluble CD40 ligand (sCD40L), interleukin (IL)-27, and soluble OX40 ligand (sOX40L). Normal PLTs secreted IL-27 and sOX40L at bioactive concentrations upon thrombin stimulation and were up regulated in association with ATRs, similar to sCD40L. Other secreted products were identified but not investigated further as their positivity was not consistent.


This study demonstrates the putative participation of PLT-derived sOX40L, IL-27, and sCD40L, which accumulate in PC supernatants, with inflammatory-type ATRs. Further studies are required to determine the clinical significance of these findings to forecast preventive measures whenever possible.