Extracorporeal photopheresis and the cellular mechanisms: Effects of 8‐methoxypsoralen and UVA treatment on red blood cells, platelets and reactive oxygen species

Background and Objectives Extracorporeal photopheresis (ECP) is a widespread cellular therapy for graft‐versus‐host disease, autoimmune diseases and Sézary disease. One of the main effects of ECP is the apoptosis of leukocytes, but the therapeutic mechanisms are not completely known. The aim of this study was to investigate the effects on red blood cells, platelets and the induction of reactive oxygen species. Materials and Methods We used human cells from healthy blood donors to simulate in vitro the composition in an apheresis bag. Cells were treated with 8‐methoxypsoralen (8‐MOP) and UVA. Red blood cell stability, platelet activity and induction of reactive oxygen species were analysed. Results After 8‐MOP and UVA treatment, the red blood cells showed high cell integrity with low levels of eryptosis and no increase of free haemoglobin or red blood cell distribution width (RDW). Red blood cell immune‐associated antigens CD59 and CD147 were hardly affected by the treatment. Platelet glycoproteins CD41, CD62P and CD63 indicated strong platelet activation after 8‐MOP and UVA treatment. Reactive oxygen species were slightly but not significantly induced by the treatment. Conclusion The effect of the ECP therapy is probably not exclusively mediated by leukocytes. Platelet activation is another striking effect caused by the treatment of the apheresis product with 8‐MOP/UVA. However, since we could hardly identify any evidence for eryptosis or haemolysis, it is unlikely that red blood cell eryptosis is part of the therapeutic mechanism. Further research on this topic seems to be promising.