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Resistance of a subset of red blood cells to clearance by antibodies in a mouse model of incompatible transfusion

Authors

  • Justine S. Liepkalns,

  • Chantel M. Cadwell,

  • Sean R. Stowell,

  • Eldad A. Hod,

  • Steven L. Spitalnik,

  • James C. Zimring


  • From the Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia; the Department of Pathology and Cell Biology, Columbia University Medical Center, and the Clinical Laboratories, New York-Presbyterian Hospital, New York, New York; and the Puget Sound Blood Center Research Institute, Seattle, Washington.

Address reprint requests to: James C. Zimring, MD, PhD, Puget Sound Blood Center Research Institute, 1551 Eastlake Avenue E, Seattle, WA 98102; e-mail: jzimring@psbc.org.

Abstract

Background

Alloimmunization to antigens on transfused red blood cells (RBCs) represents a major barrier to chronic transfusion. In extreme cases of multiple alloimmunization, clinicians may be faced with the decision of transfusing incompatible RBCs or risking death from lack of transfusion. The disastrous results of hemolytic transfusion reactions are well understood, and major pathways of clearance have been described. However, well described but poorly understood is the survival of a subset of incompatible donor RBCs during hemolysis, despite antibody binding.

Study Design And Methods

We utilize a tractable murine model of incompatible transfusion in which RBCs from transgenic donor mice expressing human glycophorin A (hGPA) are transfused into recipients passively immunized with anti-hGPA.

Results

As in humans, the majority of RBCs are cleared but a subset of incompatible donor RBCs persist in circulation, despite being bound by antibodies. Data contained herein reject the hypothesis that lack of clearance is due to insufficient antibody or overwhelming of phagocytic machinery; rather, we establish that surviving RBCs represent a distinct population resistant to clearance.

Conclusions

These studies demonstrate that surviving RBCs during incompatible transfusion can represent a population that is resistant to clearance.

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