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Author Notes:

Address correspondence to: James C. Zimring, Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Woodruff Memorial Building Suite 7107, 101 Woodruff Circle, Atlanta, Georgia 30322, USA. Phone: (404) 712-2174; Fax: (404) 727-5764; E-mail: jzimrin@emory.edu.

We thank Krista Hostetler for excellent technical assistance with platelet aggregometry.

Conflict of interest: J.C. Zimring has received a research grant unrelated to the current work from Immucor Inc.

Subjects:

Research Funding:

These studies were supported in part by NIH grant R01HL092977 (to J.C. Zimring).

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

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Journal Title:

Journal of Clinical Investigation

Volume:

Volume 119, Number 9

Publisher:

, Pages 2787-2794

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2009, American Society for Clinical Investigation

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