Antibody-Mediated Immunosuppression Can Result from RBC Antigen Loss Independent of Fcγ Receptors in Mice

Background: Prophylaxis against red blood cell (RBC) alloimmunization can be achieved by Rh immune globulin (RhIg), a polyclonal anti-RhD antibody preparation used to prevent de novo anti-RhD alloantibody formation, a process commonly termed antibody-mediated immunosuppression (AMIS). As the availability of RhIg donors can be limited and the only available immunoprophylaxis is against RhD, there is a critical need to develop monoclonal antibody alternatives to RhD and immunoprophylaxis strategies in general to other RBC alloantigens. As different monoclonal antibodies to the RhD antigen can have differential immunological outcomes,understanding the mechanism regarding how monoclonal antibodies induce AMIS can facilitate the development and accurate assessment of monoclonal antibodies against RhD and other RBC alloantigens for appropriate therapeutic activity. Recent studies suggest that AMIS may occur through alterations in the target antigen, otherwise known as antigen modulation. However, several studies suggest that AMIS may occur independent of antigen modulation. In particular, AMIS to RBCs that transgenically express the HOD (hen egg lysozyme (HEL), ovalbumin and Duffy) antigen have been shown to occur independent of the activating Fcγ receptors thought to be required for modulation of the HEL antigen. Therefore, we sought to determine whether anti-HEL monoclonal antibodies can induce antigen modulation and whether AMIS to HOD RBCs occurs via monoclonal antibody-induced alterations to the target antigen.