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Reduced MHC alloimmunization and partial tolerance protection with pathogen reduction of whole blood
Author(s) -
Jackman Rachael P.,
Muench Marcus O.,
Inglis Heather,
Heitman John W.,
Marschner Susanne,
Goodrich Raymond P.,
Norris Philip J.
Publication year - 2017
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.13895
Subject(s) - leukoreduction , immunology , whole blood , cytokine , immune system , major histocompatibility complex , antigen , medicine , blood transfusion
BACKGROUND Allogeneic blood transfusion can result in an immune response against major histocompatibility complex (MHC) antigens, potentially complicating future transfusions or transplants. We previously demonstrated that pathogen reduction of platelet‐rich plasma (PRP) with riboflavin and ultraviolet 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 the prevention of alloimmunization. STUDY DESIGN AND METHODS BALB/cJ mice were transfused with untreated or UV+R‐treated, allogeneic C57Bl/6J whole blood with or without leukoreduction. Mice were evaluated for donor‐specific antibodies, ex vivo splenocyte cytokine responses, and changes in the frequency of regulatory T (T reg ) 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‐treated 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 T reg 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 T reg cells.