Riboflavin‐ultraviolet light pathogen reduction treatment does not impact the immunogenicity of murine red blood cells

Tormey, Christopher A.; Santhanakrishnan, Manjula; Smith, Nicole H.; Liu, Jingchun; Marschner, Susanne; Goodrich, Raymond P.; Hendrickson, Jeanne E.

doi:10.1111/trf.13432

Cited by 9 publications

(6 citation statements)

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“…In vivo survival was further shown to be similar in both untreated and Mirasol‐treated RBCs transfused in baboons; the transfusion of Mirasol‐treated baboon RBCs did not show any evidence of detrimental immune responses . In mice, Mirasol treatment showed a reduction in long‐term posttransfusion RBC survival despite its minimal influence on RBC alloimmunization; this observation points to its relative safety from an immunohematologic standpoint . Intriguingly, this pattern of reduced survival of Mirasol‐treated RBCs is particularly reminiscent of the eryptotic phenotype in mice that show enhanced susceptibility of RBCs to PS exposure fostering their accelerated clearance from the circulation …”

Section: Discussionmentioning

confidence: 82%

Pathogen inactivation by riboflavin and ultraviolet light illumination accelerates the red blood cell storage lesion and promotes eryptosis

et al. 2016

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Section: Discussionmentioning

confidence: 82%

Pathogen inactivation by riboflavin and ultraviolet light illumination accelerates the red blood cell storage lesion and promotes eryptosis

et al. 2016

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“…Moreover, this treatment abrogates the ability of contaminating WBC to present the antigen, inhibiting T‐cell proliferation, cytokine production and finally preventing transfusion‐associated graft‐versus‐host disease (ta‐GVHD) . The toxicological safety of WB treated with RF+UV has been demonstrated both in vitro as in animal studies .…”

Section: Introductionmentioning

confidence: 99%

The pathogen‐reduced red blood cell suspension: single centre study of clinical safety and efficacy in children with oncological and haematological diseases

et al. 2019

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Background Transmission of pathogens through blood transfusion is still of great concern to clinicians, patients and blood providers. Pathogen reduction technologies (PRT) have been successfully applied for the treatment of labile blood components, such as plasma, platelets and whole blood (WB), which are now used in routine in many countries. We report the clinical evaluation of suspension of red blood cells (RBC‐S) derived from the WB treated with riboflavin and UV light (RF+UV). Study Design and Methods Seventy paediatric patients (0·3–17·1 years old) suffering from different malignant disorders were recruited and assigned to two groups: the control group (C) received transfusions of γ‐irradiated RBC‐S. The experimental group (T) received RBC‐S derived from WB, treated with RF+UV. Clinical efficacy was evaluated during follow‐up periods by Hb and Ht increments, and needs for transfusion support. Safety was assessed through active surveillance, recording post‐transfusion reactions, anti‐erythrocyte's antibody formation, haptoglobin and serum potassium levels. Results The clinical efficacy of RBC‐S in both groups was similar: mean post‐transfusion Hb concentration (101·6 ± 7·57 g/l vs. 100 ± 8·3 g/l; P = 0·43), and Ht level (28·5 ± 2·42% vs. 28·2 ± 2·7%; P = 0·66). Transfusion of pathogen‐reduced RBC‐S did not increase the frequency of transfusion reactions and did not induce an excessive immune response in the follow‐up period. Conclusion Transfusion of RBC‐S, obtained from pathogen‐reduced WB, is a promising method to increase the safety of blood component therapy for paediatric patients with malignant disorders without affecting clinical efficacy. A randomized clinical trial including more patients should follow this pilot study to confirm its results.

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“…Little is known about the impact of whole blood pathogen reduction on alloimmunization. A recent study using UV+R pathogen reduction found that it did not prevent alloimmunization against RBC antigens in mice . Responses to MHC alloantigens may be different for several reasons, including the possibility of direct recognition by T cells and expression on WBCs and platelets rather than RBCs, which are impacted differently by treatment.…”

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confidence: 99%

Reduced MHC alloimmunization and partial tolerance protection with pathogen reduction of whole blood

et al. 2016

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BACKGROUND Allogeneic blood transfusion can result in an immune response against major histocompatibility complex (MHC) antigens, potentially complicating future transfusions or transplants. We have previously shown that pathogen reduction of platelet-rich plasma (PRP) with riboflavin and UV light (UV+R) can prevent alloimmunization in mice. A similar pathogen reduction treatment is currently under development for the treatment of whole blood using riboflavin and a higher dose of UV light. We sought to determine the effectiveness of this treatment in prevention of alloimmunization. STUDY DESIGN AND METHODS BALB/c mice were transfused with untreated or UV+R treated allogeneic C57Bl/6 whole blood with or without leukoreduction. Mice were evaluated for donor specific antibodies and ex vivo splenocyte cytokine responses, as well as for changes in the frequency of regulatory T (Treg) cells. RESULTS UV+R treatment blocked cytokine priming and reduced anti-MHC alloantibody responses to transfused whole blood. Leukoreduction reduced alloantibody levels in both the untreated and UV+R groups. Mice transfused with UV+R treated whole blood had reduced alloantibody and cytokine responses when subsequently transfused with untreated blood from the same donor type. This reduction in responses was not associated with increased Treg cells. CONCLUSIONS Pathogen reduction of whole blood with UV+R significantly reduces, but does not eliminate the alloimmune response. Exposure to UV+R treated whole blood transfusion does appear to induce tolerance to alloantigens resulting in reduced anti-MHC alloantibody and cytokine responses to subsequent exposures to the same alloantigens. This tolerance does not appear to be driven by an increase in Treg cells.

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Riboflavin‐ultraviolet light pathogen reduction treatment does not impact the immunogenicity of murine red blood cells

Cited by 9 publications

References 36 publications

Pathogen inactivation by riboflavin and ultraviolet light illumination accelerates the red blood cell storage lesion and promotes eryptosis

Pathogen inactivation by riboflavin and ultraviolet light illumination accelerates the red blood cell storage lesion and promotes eryptosis

The pathogen‐reduced red blood cell suspension: single centre study of clinical safety and efficacy in children with oncological and haematological diseases

Reduced MHC alloimmunization and partial tolerance protection with pathogen reduction of whole blood

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