Evaluation of White Blood Cell- and Platelet-Derived Cytokine Accumulation in MIRASOL-PRT-Treated Platelets

Abstract

Background: Soluble mediators in platelet concentrates (PCs) released from contaminating white blood cells (WBCs) and platelets (PLTs) themselves are supposed to promote allergic and non-hemolytic febrile transfusion reactions in the recipient. Pathogen reduction technologies (PRTs) prevent replication and proliferation of pathogens as well as of WBCs, and may reduce cytokine accumulation in PCs during storage and prevent adverse events after PLT transfusion. On the other hand, such treatments may also lead to increased cytokine production by stimulation of WBCs or PLTs due to the photochemical or photodynamical process itself. Material and Methods: 12 triple-dose PLT apheresis collections were leukoreduced by the process-controlled leukoreduction system of the Trima Accel machine and split into 3 units undergoing Mirasol-PRT treatment (M) or gamma irradiation (X) or remaining untreated (C). During storage for up to 7 days, PLT activation, WBC-derived Th-1/2, and inflammatory as well as PLT-derived cytokines were measured by cytometric bead array and enzymelinked immunosorbent assay, respectively. Results: Independent of treatment, all PLT products exhibited low levels of WBC-associated cytokines near or below assay detection limits. WBC-associated cytokines were not elevated by Mirasol-PRT treatment. PLT-derived cytokines were detected at higher levels and increased significantly during storage in all units. Most likely due to higher PLT activation, M units showed significantly higher levels of PLT-derived cytokines compared to untreated and gamma-irradiated units on day 5 of storage. Conclusion: In all PCs, PLTs themselves were the main source of cytokine release. Mirasol-PRT treatment was associated with a significantly increased PLT activation and accumulation of PLT-derived cytokines during storage, without affecting WBC-derived cytokines relative to controls.

Inactivation of human white blood cells in platelet products after pathogen reduction technology treatment in comparison to gamma irradiation

“…PLT‐derived cytokines/chemokines were elevated after PRT treatment and 8 days of storage, reflecting PLT activation and cytokine release from α‐granules or de novo synthesis. These results are in agreement with previous findings reporting that prestorage leukoreduction, gamma irradiation, or PRT treatment could prevent accumulation of TGF‐β1, RANTES, and PF4 21‐23 . RANTES levels associated with allergic reactions have been reported to range from approximately 200 to 1000 ng/mL with a median of 650 ng/mL 24 .…”

In vitro study of platelet function confirms the contribution of the ultraviolet B (UVB) radiation in the lesions observed in riboflavin/UVB‐treated platelet concentrates

“…Altogether, these data suggest that the Mirasol treatment impacts important protein kinases involved in signal transduction, probably via the generation of ROS. In addition, the Mirasol treatment has been associated with an accumulation of PLT‐derived cytokines during storage, likely caused by PLT destruction and/or PLT degranulation or cytokine de novo synthesis . The same has been observed in amotosalen/UVA‐treated PLTs .…”

Study of CD69 antigen expression and integrity of leukocyte cellular membrane in stored platelet concentrates following irradiation and treatment with Mirasol® PRT System

“…The concentration of these soluble factors varies depending on the method of PC preparation and leukocyte content in the blood components. 18 To date, gamma irradiation has been the main technology used for inactivation of residual lymphocytes in transfusion-dedicated blood components and for TAGvHD prevention. Irradiation technology, however, is not effective for pathogen reduction.…”