IMMUNOHEMATOLOGY: Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment

Abstract

BACKGROUND-Donor white blood cells (WBCs) present in transfusion products can lead to immune sequelae such as production of anti-HLA antibodies or GVHD in susceptible transfusion recipients. Eliminating the immunogenicity of blood products may prove to be of clinical benefit, particularly in patients requiring multiple transfusions in whom allosensitization is common. This study examines a method of pathogen reduction based on UV light illumination in the presence of riboflavin. In addition to pathogens, WBCs treated with this system are also affected and fail to stimulate proliferation of allogeneic PBMCs in vitro.

Pathogen Reduction Technology Treatment of Platelets, Plasma and Whole Blood Using Riboflavin and UV Light

“…The average 1-hour corrected count increment (CCI) benefits of Mirasol treatment, beyond the prevention of TAGvHD, may come from the prevention of alloimmunization and cytokine production (table 4). Data currently available indicate that Mirasol-treated leukocytes are incapable of stimulating or binding to allogeneic cells [38], that they prevent alloimmunization in an animal model [39] and that they mediate less of a decrease in platelet count increments with increasing numbers of transfusions in the clinical setting [37]. Elimination of cytokine production is beneficial because cytokine accumulation in stored platelet products has been associated with the occurrence of febrile nonhemolytic transfusion reactions.…”

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

“…Similar results were reported by Jackman et al, who used amine reactive dye; only about 5% of viable cells were found in the M treated PCs (already on storage day 3) while about 50% were reported in the R PCs. 19 According to Diacovo et al, an interaction occurs between lymphocytes and activated platelets that results in lymphocyte activation and higher CD69 expression. 20 Pόcsik et al reported an increase in the expression of the interleukin-2 receptor, CD26, activation-inducer molecule (AIM, CD69) and transferring receptors (CD71) 3 days after allotransfusion of platelets, which indicated an important functional molecule expression on lymphocytes activated by allogenic platelets.…”

The long and winding road to pathogen reduction of platelets, red blood cells and whole blood

“…Most studies using the above classical methods showed PRT effects indicative of low to moderate loss of platelet in vitro function as compared to untreated platelets, progressively expressed during 5 to 7 days of storage (van Rhenen et al , ; Jansen et al , ; Picker et al , ; Perez‐Pujol et al , ; Apelseth et al , ; Lozano et al , ; Picker et al , ; Castrillo et al , ; Jackman et al , ; Sandgren et al , ; Hechler et al , ; Abonnenc et al , ; van Aelst et al , ; Johnson et al , ). However, some studies reported conflicting results, possibly due to differences in methods for platelet collection and preparation, use of 100% plasma or a mixture of plasma and platelet additive solution as storage media, donor‐to‐donor variability and variables of the testing protocols.…”

“…A specific question raised by the findings of the RCTs was whether the increased frequency of refractoriness was only due to platelet storage lesions following PRT treatment and to the resulting decreased post‐transfusion recovery, or if it was also associated with the development of alloimmunization to human leucocyte antigens (HLA) or other platelet antigens. The latter possibility was largely not predicted based on in vitro studies (Jackman et al , ), in vivo animal transfusion models (Muench et al , ; Slichter et al , ) and early RCTs (van Rhenen et al , ; McCullough et al , ; Mirasol Clinical Evaluation Study Group, ). More recently, insufficient statistical power prevented the collection of unequivocal evidence on PRT effect on HLA alloimmunization from one study testing samples from recipients of intercept and Mirasol‐treated platelets enrolled in the Italian Platelet Technology Assessment Study (IPTAS) RCT (Norris et al , ), whereas investigators using a larger set of samples from recipients of Mirasol‐treated platelets enrolled in the Pathogen Reduction Evaluation and Predictive Analytical Rating Score (PREPAReS) RCT reported the conclusion that their data ‘clearly indicate that Mirasol pathogen inactivation does not prevent HLA Class I or II alloimmunization after platelet transfusions’ (Saris et al , ).…”