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Blood, 1 April 2007, Vol. 109, No. 7, pp. 3099-3107.
Prepublished online as a Blood First Edition Paper on November 21, 2006; DOI 10.1182/blood-2006-08-040139.


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TRANSFUSION MEDICINE

Mouse models of IgG- and IgM-mediated hemolysis

David A. Schirmer1, Shuh-Chyung Song1, Jeffrey P. Baliff2, Stephanie O. Harbers3, Raphael A. Clynes3, Anna Krop-Watorek4, Gregory R. Halverson5, Marcin Czerwinski4, and Steven L. Spitalnik1

1 Department of Pathology, Columbia University, New York, NY; 2 Department of Pathology and Laboratory Medicine, University of Rochester, NY; 3 Department of Microbiology, Columbia University, New York, NY; 4 Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland; 5 Department of Immunochemistry, New York Blood Center, New York, NY

Well-characterized mouse models of alloimmune antibody-mediated hemolysis would provide a valuable approach for gaining greater insight into the pathophysiology of hemolytic transfusion reactions. To this end, mouse red blood cells (mRBCs) from human glycophorin A transgenic (hGPA-Tg) donor mice were transfused into non-Tg recipients that had been passively immunized with IgG or IgM hGPA-specific monoclonal antibodies (mAbs). In this novel murine "blood group system," mRBCs from hGPA-Tg mice are "antigen positive" and mRBCs from non-Tg mice are "antigen negative." Passive immunization of non-Tg mice with the IgG1 10F7 and IgG3 NaM10-2H12 anti-hGPA mAbs each induced rapid clearance of incompatible transfused hGPA-Tg-mRBCs in a dose-response manner. Using various knockout mice as transfusion recipients, both the complement system and activating Fc{gamma} receptors were found to be important in the clearance of incompatible mRBCs by each of these IgG mAbs. In addition, the IgM E4 anti-hGPA mAb induced complement-dependent intravascular hemolysis of transfused incompatible hGPA-Tg-mRBCs accompanied by gross hemoglobinuria. These initial studies validate the relevance of these new mouse models for addressing important questions in the field of transfusion medicine.


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