Submitted March 14, 2007
Accepted April 19, 2007
Epitope specificity and isotype of monoclonal anti-D antibodies dictate their ability to inhibit phagocytosis of opsonized platelets
Mimi Kjaersgaard, Rukhsana Aslam, Michael Kim, Edwin R. Speck, John Freedman, Donald I.H. Stewart, Erik J. Wiersma, and John W. Semple*
Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark
University of Toronto, Canadian Blood Services, Toronto, Ontario, Canada
Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, Ontario, Canada
Dept of Laboratory Medicine, St. Michael's Hospital, Toronto, Ontario, Canada
Dept. of Research, Cangene Corporation, Mississauga, Ontario, Canada
Depts of Pharmacology, Medicine, and Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada
* Corresponding author; email: semplej{at}smh.toronto.on.ca.
Rh immune globulin (WinRho®SDF) is an effective treatment for autoimmune thrombocytopenic purpura (AITP), however, maintaining a sustained supply for its use in AITP and its primary indication, hemolytic disease of the newborn, makes the development of alternative reagents desirable. We compared WinRho®SDF and six human monoclonal anti-D antibodies (MoAnti-D) with differing isotypes and specificities for their ability to opsonize erythrocytes and inhibit platelet phagocytosis in an in vitro assay. Results demonstrated that opsonization of erythrocytes with WinRho®SDF significantly (p<0.0001) reduced phagocytosis of fluroescently-labeled opsonized platelets in an Fc-dependent manner. Of the MoAnti-D that shared specificity but differed in isotype, only IgG3 antibodies could significantly (p<0.0001) inhibit platelet phagocytosis. In contrast, two MoAnti-D shared isotype and differed in specificity, however, only one could significantly (p<0.0001) inhibit platelet phagocytosis. The results suggest that MoAnti-D epitope specificity and isotype are important requirements to optimally inhibit platelet phagocytosis.
