Submitted April 2, 2007
Accepted June 1, 2007
Non-hemolytic antigen-loss from RBCs requires cooperative binding of multiple antibodies recognizing different epitopes
James C. Zimring*, Chantel M. Cadwell, Traci E. Chadwick, Steven L. Spitalnik, David A. Schirmer, Tao Wu, Charles A. Parkos, and Christopher D. Hillyer
Center for Transfusion and Cellular Therapies, Dept of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United States
Dept of Pathology, College of Physicians & Surgeons, Columbia University, New York, NY, United States
Epithelial Pathology Research Unit, Dept of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United States
* Corresponding author; email: jzimrin{at}emory.edu.
Transfusion of crossmatch incompatible RBCs can result in antibody mediated hemolysis. However, in some patients, crossmatch incompatible RBCs lose the incompatible antigen from their surface, and then circulate normally ("antigen-loss"). Although antigen-loss has been reported in the settings of autoimmune hemolytic anemia and transfusion of crossmatch incompatible RBCs, mechanistic understanding of this phenomenon is limited. Using an in vivo murine model of antigen-loss, we report that, unlike polyclonal antisera, monoclonal antibodies did not induce antigen-loss. However, the combination of two monoclonal antibodies that recognized separate epitopes on the same antigen induced antigen-loss. This was not due to an increased number of Fc domains bound to the cell surface, as antigen-loss still occurred when combining intact monoclonal IgG and F(ab')2 fragments recognizing different epitopes. Together, these data lead to the hypothesis that antigen-antibody crosslinking is required for nonhemolytic antigen-loss to occur.
