Reduced alloimmunization in mice following repeated transfusion with pathogen‐reduced platelets

Muench, Marcus O.; Heitman, John W.; Inglis, Heather C.; Fomin, Marina E.; Marschner, Susanne; Goodrich, Raymond P.; Norris, Philip J.; Jackman, Rachael P.

doi:10.1111/trf.13579

Cited by 20 publications

(42 citation statements)

References 45 publications

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“…Antibodies were measured as previously described . Briefly, C57Bl/6J splenocytes (donor‐type target cells) were preincubated with an anti‐FcR blocking antibody, then incubated with the serum to be screened, and washed.…”

Section: Methodsmentioning

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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Section: Methodsmentioning

confidence: 99%

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

et al. 2016

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“…In efforts to improve transfusion safety, pathogen reduction technologies (PRT) are being implemented . In addition to inactivating bacteria, parasites and viruses, including CMV, PRT brings other benefits: replacement of gamma irradiation by white blood cell (WBC) inactivation, which eliminates the risk of transfusion‐transmitted GVHD; a lower frequency of febrile and allergic transfusion reactions and possibly a reduction in alloimmunization and preventing PLT refractoriness, which according to a recent publication still needs to be confirmed by evidence from clinical practice …”

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confidence: 99%

Use and safety of riboflavin and UV light‐treated platelet transfusions in children over a five‐year period: focusing on neonates

2019

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BACKGROUND: There are very few published reports about the use and safety of pathogen reduction technology (PRT) based on riboflavin and UV light for platelet (PLT) transfusion in children. STUDY DESIGN AND METHODS:A two-part study was conducted: 1) a study investigating the safety of PLTs treated with riboflavin and UV light-PRT transfused to 379 children and 1,980 adults over a 5-year period; 2) an observational study evaluating the efficacy of PLT use in 132 neonates transfused with PRT-treated PLT compared with 99 neonates receiving standard PLTs over two 5-year periods. RESULTS:The rate of adverse reactions related to transfusions with PRT-treated PLTs was found to be slightly higher in adults than in children, although not statistically significant (0.19% vs. 0.12%; p = 0.85). All PLT transfusion events in children were mild. From 2013 to 2017, 379 children received 4,236 riboflavin and UV light-treated PLTs. Hemato-oncology patients received the most PLT transfusions (61.2%), followed by critically ill children in the Pediatric Intensive Care Unit (PICU) (24.6%), and neonates in the Neonatal Intensive Care Unit (NICU) (10.5%). A significant increase in PLT transfusions was found in 132 neonates transfused with 458 PRT-treated PLTs compared with 99 neonates receiving 176 standard PLTs, measuring PLT use/patient (p = 0.031) and total PLT dose/patient (p = 0.041). CONCLUSIONS: Riboflavin and UV light-based PRTfor PLTs seems to be safe for children. Neonates required a higher number of PLT transfusions when these were PRT-treated rather than standard. A longterm follow-up for chronically transfused children and randomized clinical trials are needed.d'Investigació Sanitària Illes Balears (IdISBa), and the

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“…Pathogen reduction technology (PRT) for blood components can provide significant benefits: 1) enhancing blood safety through the inactivation of viruses, bacteria, and parasites; 2) protecting the blood supply from emerging infectious agents for which laboratory tests might still be unavailable; 3) replacing gamma irradiation by inactivating white blood cells (WBCs) not removed by leukoreduction and thereby eliminating the risk of transfusion‐transmitted graft‐versus‐host disease; 4) preventing alloimmunization and avoiding platelet (PLT) refractoriness; 5) reducing the frequency of reactions related to PLT transfusions; and 6) in some settings improving blood supply logistics by increasing the PLT storage time . Thus, PRT that inactivates a broad range of pathogens provides an opportunity to substantially improve transfusion safety, not only by reducing bacterial contamination and sepsis but especially by preventing transfusion‐transmissible emerging infectious agents such as the Zika virus …”

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Our experience in riboflavin and ultraviolet light pathogen reduction technology for platelets: from platelet production to patient care

2018

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Reduced alloimmunization in mice following repeated transfusion with pathogen‐reduced platelets

Abstract: Pathogen reduction significantly reduces alloimmunization in repeatedly transfused mice and combined with leukoreduction provides a high level of protection from alloimmunization.

Cited by 20 publications

References 45 publications

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

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

Use and safety of riboflavin and UV light‐treated platelet transfusions in children over a five‐year period: focusing on neonates

Our experience in riboflavin and ultraviolet light pathogen reduction technology for platelets: from platelet production to patient care

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