Reticulocytes in donor blood units enhance red blood cell alloimmunization.

Reticulocytes in donor blood units enhance red blood cell alloimmunization.
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DOI:
10.3324/haematol.2023.282815
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发表时间:
2023-10-01
期刊:
影响因子:
10.1
通讯作者:
Hudson, Krystalyn E.
Hudson, Krystalyn E.
中科院分区:
医学1区
文献类型:
--
作者:
Thomas, Tiffany A.;Qiu, Annie;Kim, Christopher Y.;Gordy, Dominique E.;Miller, Anabel;Tredicine, Maria;Dzieciatkowska, Monika;Dei Zotti, Flavia;Hod, Eldad A.;D'Alessandro, Angelo;Zimring, James C.;Spitalnik, Steven L.;Hudson, Krystalyn E.

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Although red blood cell (RBC) transfusions save lives, some patients develop clinically-significant alloantibodies against donor blood group antigens, which then have adverse effects in multiple clinical settings. Few effective measures exist to prevent RBC alloimmunization and/or eliminate alloantibodies in sensitized patients. Donor-related factors may influence alloimmunization; thus, there is an unmet clinical need to identify which RBC units are immunogenic. Repeat volunteer blood donors and donors on iron supplements have elevated reticulocyte counts compared to healthy non-donors. Early reticulocytes retain mitochondria and other components, which may act as danger signals in immune responses. Herein, we tested whether reticulocytes in donor RBC units could enhance RBC alloimmunization. Using a murine model, we demonstrate that transfusing donor RBC units with increased reticulocyte frequencies dose-dependently increased RBC alloimmunization rates and alloantibody levels. Transfusing reticulocyte-rich RBC units was associated with increased RBC clearance from the circulation and a robust proinflammatory cytokine response. As compared to previously reported post-transfusion RBC consumption patterns, erythrophagocytosis from reticulocyte-rich units was increasingly performed by splenic B cells. These data suggest that reticulocytes in a donated RBC unit impact the quality of blood transfused, are targeted to a distinct compartment, and may be an underappreciated risk factor for RBC alloimmunization.
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