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Transfusion of minor histocompatibility antigen–mismatched platelets induces rejection of bone marrow transplants in mice
Seema R. Patel, … , Arielle Medford, James C. Zimring
Seema R. Patel, … , Arielle Medford, James C. Zimring
Published August 10, 2009
Citation Information: J Clin Invest. 2009;119(9):2787-2794. https://doi.org/10.1172/JCI39590.
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Research Article Hematology Article has an altmetric score of 3

Transfusion of minor histocompatibility antigen–mismatched platelets induces rejection of bone marrow transplants in mice

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Abstract

Bone marrow transplantation (BMT) represents a cure for nonmalignant hematological disorders. However, compared with the stringent conditioning regimens used when performing BMT to treat hematological malignancies, the reduced intensity conditioning regimen used in the context of nonmalignant hematological disorders leads to substantially higher rates of BMT rejection, presumably due to an intact immune system. The relevant patient population typically receives transfusion support, often including platelets, and the frequency of BMT rejection correlates with the frequency of transfusion. Here, we demonstrate that immunity to transfused platelets contributes to subsequent BMT rejection in mice, even when the BMT donor and recipient are MHC matched. We used MHC-matched bone marrow because, although immunity to transfused platelets is best characterized in relation to HLA-specific antibodies, such antibodies are unlikely to play a role in clinical BMT rejection that is HLA matched. However, bone marrow is not matched in the clinic for minor histocompatibility antigens, such as those carried by platelets, and we report that transfusion of minor histocompatibility antigen–mismatched platelets induced subsequent BMT rejection. These findings indicate previously unappreciated sequelae of immunity to platelets in the context of transplantation and suggest that strategies to account for minor histocompatibility mismatching may help to reduce the chance of BMT rejection in human patients.

Authors

Seema R. Patel, Chantel M. Cadwell, Arielle Medford, James C. Zimring

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Figure 2

Quality of isolated LR-PLT concentrates.

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Quality of isolated LR-PLT concentrates.
(A–C) The quantity of PLTs, rbc...
(A–C) The quantity of PLTs, rbc, and leukocytes was assessed using cell surface markers CD41 and TER119 (A and B) or nucleic acid binding PI (C), respectively. Isotype controls (rat IgG1 for PLTs and rat IgG2b for rbc) and unstained samples were also enumerated to control for nonspecific signal (B and C, respectively). Whole blood samples (A and C) were included for gating purposes. (D) Functionality of isolated PLTs. B6, BALB.B, and BALB/c PLTs were exposed to collagen and measured for percentage of aggregation over time using an aggregometer. PLTs without collagen exposure were included to control for spontaneous aggregation. (E) In vivo survival of LR-PLT products. PLTs from EGFP transgenic mice were transfused into naive B6 recipients and tracked over time. Data represent mean ± SEM. Representative flow cytometry is presented; the left plot utilizes an untransfused mouse to establish background, while the right plot illustrates EGFP+CD41+ PLTs from a transfused recipient. Parts A–C demonstrate the gating strategy used for quantifying each cell subset. Numbers indicate the percentage of the gated population as a function of total events. All panels show representative data from experiments reproduced at least 3 times.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 1 clinical guideline sources
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