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Immune modulation and lack of alloimmunization following transfusion with pathogen-reduced platelets in mice

Authors

  • Rachael P. Jackman,

    1. Blood Systems Research Institute, San Francisco, California
    2. Department of Laboratory Medicine, University of California, San Francisco, California
    3. Terumo BCT Biotechnologies, Lakewood, Colorado
    4. Department of Medicine, University of California, San Francisco, California
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  • Marcus O. Muench,

    1. Blood Systems Research Institute, San Francisco, California
    2. Department of Laboratory Medicine, University of California, San Francisco, California
    3. Terumo BCT Biotechnologies, Lakewood, Colorado
    4. Department of Medicine, University of California, San Francisco, California
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  • John W. Heitman,

    1. Blood Systems Research Institute, San Francisco, California
    2. Department of Laboratory Medicine, University of California, San Francisco, California
    3. Terumo BCT Biotechnologies, Lakewood, Colorado
    4. Department of Medicine, University of California, San Francisco, California
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  • Heather C. Inglis,

    1. Blood Systems Research Institute, San Francisco, California
    2. Department of Laboratory Medicine, University of California, San Francisco, California
    3. Terumo BCT Biotechnologies, Lakewood, Colorado
    4. Department of Medicine, University of California, San Francisco, California
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  • Jacqueline P. Law,

    1. Blood Systems Research Institute, San Francisco, California
    2. Department of Laboratory Medicine, University of California, San Francisco, California
    3. Terumo BCT Biotechnologies, Lakewood, Colorado
    4. Department of Medicine, University of California, San Francisco, California
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  • Susanne Marschner,

    1. Blood Systems Research Institute, San Francisco, California
    2. Department of Laboratory Medicine, University of California, San Francisco, California
    3. Terumo BCT Biotechnologies, Lakewood, Colorado
    4. Department of Medicine, University of California, San Francisco, California
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  • Raymond P. Goodrich,

    1. Blood Systems Research Institute, San Francisco, California
    2. Department of Laboratory Medicine, University of California, San Francisco, California
    3. Terumo BCT Biotechnologies, Lakewood, Colorado
    4. Department of Medicine, University of California, San Francisco, California
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  • Philip J. Norris

    1. Blood Systems Research Institute, San Francisco, California
    2. Department of Laboratory Medicine, University of California, San Francisco, California
    3. Terumo BCT Biotechnologies, Lakewood, Colorado
    4. Department of Medicine, University of California, San Francisco, California
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  • This work was supported by Terumo BCT Biotechnologies and Department of the Army under Award W81XWH-09-2-0100. The U.S. Army Medical Research Acquisition Activity, Fort Detrick, MD, is the awarding and administering office.
  • The content of the information contained herein does not necessarily reflect the position or the policy of the government and no official endorsement should be inferred.

Address reprint requests to: Rachael P. Jackman, 270 Masonic Avenue, San Francisco, CA 94118; e-mail: rjackman@bloodsystems.org.

Abstract

Background

Transfusion of allogeneic blood products can lead to alloimmunization, impacting success of subsequent transfusions and solid organ transplants. Pathogen reduction using riboflavin and ultraviolet B (UVB) light has been shown to eliminate the immunogenicity of white blood cells (WBCs) in vitro through down regulation of surface adhesion molecules, effectively blocking cell–cell conjugation and direct presentation. We sought to determine if this loss of immunogenicity is extended in vivo where indirect presentation of allogeneic antigens can occur.

Study Design and Methods

BALB/cJ mice were transfused with either untreated or riboflavin and UVB–treated C57Bl/6J platelet-rich plasma (PRP) containing WBCs. Circulating alloantibody and allospecific splenocyte cytokine responses were measured.

Results

Pathogen reduction of allogeneic WBC-enriched PRP using riboflavin and UVB light before transfusion prevented alloimmunization, with a loss of both alloantibody generation and priming of secondary cytokine responses ex vivo. When mice given treated transfusions were subsequently given untreated transfusions, they produced normal levels of alloantibodies but had reduced secondary cytokine responses ex vivo. This immune modulation was antigen specific and was dependent on the presence of WBCs in the treated product.

Conclusions

UVB plus riboflavin treatment of WBC-enriched PRP effectively blocks alloimmunization and modulates immune responses to subsequent exposures.

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