title: Antibody-mediated immune suppression is improved when blends of anti-RBC monoclonal antibodies are used in mice.
abstract: Although the prevention of hemolytic disease of the fetus and newborn is highly effective using polyclonal anti-D, a recombinant alternative is long overdue. Unfortunately, anti-D monoclonal antibodies have been, at best, disappointing. To determine the primary attribute defining an optimal antibody, we assessed suppression of murine red blood cell (RBC) immunization by single-monoclonal antibodies vs defined blends of subtype-matched antibodies. Allogeneic RBCs expressing the HOD antigen (hen egg lysozyme [HEL]-ovalbumin-human transmembrane Duffy(b)) were transfused into naïve mice alone or together with selected combinations of HEL-specific antibodies, and the resulting suppressive effect was assessed by evaluating the antibody response. Polyclonal HEL antibodies dramatically inhibited the antibody response to the HOD antigen, whereas single-monoclonal HEL antibodies were less effective despite the use of saturating doses. A blend of monoclonal HEL-specific antibodies reactive with different HEL epitopes significantly increased the suppressive effect, whereas a blend of monoclonal antibodies that block each other's binding to the HEL protein did not increase suppression. In conclusion, these data show that polyclonal antibodies are superior to monoclonal antibodies at suppressing the immune response to the HOD cells, a feature that can be completely recapitulated using monoclonal antibodies to different epitopes.
authors.affiliation: The Canadian Blood Services Centre for Innovation, Department of Laboratory Medicine and the Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, and.
authors.forename: Lidice
authors.initials: L
authors.lastname: Bernardo
authors.affiliation: Department of Laboratory Medicine and the Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, and.
authors.forename: Alaa
authors.initials: A
authors.lastname: Amash
authors.affiliation: Department of Laboratory Medicine and the Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, and.
authors.forename: Danielle
authors.initials: D
authors.lastname: Marjoram
authors.affiliation: The Canadian Blood Services Centre for Innovation, Department of Laboratory Medicine and the Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, and Department of Medicine and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Lazarus
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002645:Chickens; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D009113:Muramidase