A novel human CD32 mAb blocks experimental immune haemolytic anaemia in FcγRIIA transgenic mice

A fully human IgGI kappa antibody (MDE-8) was generated, which recognised Fc-gamma receptor IIa (FcyRIIa) molecules on CD32 transfectants, peripheral blood monocytes, polymorphonuclear cells and platelets. This antibody blocked FcγRIIa ligand-binding via its F(ab')2 fragment. Overnight incubation of monocytes with F(ab')2 fragments of MDE-8 leads to a c. 60% decrease in cell surface expression of FcyRIIa. MDE-8 whole antibody induced a concomitant c. 30% decrease of FcyRI on THP-1 cells and monocytes. In humans FcyRIIa plays an important role in the clearance of antibody-coated red blood cells in vivo. As an equivalent of FcyRIIa does not exist in mice, the in vivo effect of MDE-8 was studied in an FcγRIIa transgenic mouse model. In these mice, antibody-induced anaemia could readily be blocked by MDE-8. These data document a new human antibody that effectively blocks FcγRIIa, induces modulation of both FcγRIIa and FcyRI from phagocytic cells, and ameliorates antibody-induced anaemia in vivo.