title: Epitope specificity and isotype of monoclonal anti-D antibodies dictate their ability to inhibit phagocytosis of opsonized platelets.
abstract: Rh immune globulin (WinRho SDF; Cangene, Mississauga, ON, Canada) is an effective treatment for autoimmune thrombocytopenic purpura; however, maintaining a sustained supply for its use in autoimmune thrombocytopenic purpura and its primary indication, hemolytic disease of the newborn, makes the development of alternative reagents desirable. We compared Rh immune globulin and 6 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 Rh immune globulin significantly (P < .001) reduced phagocytosis of fluorescently 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 < .001) inhibit platelet phagocytosis. In contrast, 2 MoAnti-D shared isotypes and differed in specificity; however, only one could significantly (P < .001) inhibit platelet phagocytosis. The results suggest that MoAnti-D epitope specificity and isotypes are critical requirements for optimal inhibition of opsonized platelet phagocytosis.
authors: Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark.
authors: Mimi
authors: M
authors: Kjaersgaard
authors: Rukhsana
authors: R
authors: Aslam
authors: Michael
authors: M
authors: Kim
authors: Edwin R
authors: ER
authors: Speck
authors: John
authors: J
authors: Freedman
authors: Donald I H
authors: DI
authors: Stewart
authors: Erik J
authors: EJ
authors: Wiersma
authors: John W
authors: JW
authors: Semple
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D016824:Antigens, Human Platelet / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007132:Immunoglobulin Isotypes; D009895:Opsonin Proteins; D010587:Phagocytosis; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology* / Q000378:metabolism; D012203:Rh Isoimmunization; D018029:Rho(D) Immune Globulin / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D016824:Antigens, Human Platelet; D001323:Autoantibodies; D000939:Epitopes; D007132:Immunoglobulin Isotypes; D009895:Opsonin Proteins; D018029:Rho(D) Immune Globulin