A novel human CD32 mAb blocks experimental immune haemolytic anaemia in Fc γRIIA transgenic mice.

A fully human IgG1 kappa antibody (MDE-8) was generated, which recognised Fc-gamma receptor IIa (Fc γRIIa) molecules on CD32 transfectants, peripheral blood monocytes, polymorphonuclear cells and platelets. This antibody blocked Fc γRIIa 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 Fc γRIIa. MDE-8 whole antibody induced a concomitant c. 30% decrease of Fc γRI on THP-1 cells and monocytes. In humans Fc γRIIa plays an important role in the clearance of antibody-coated red blood cells in vivo. As an equivalent of Fc γRIIa does not exist in mice, the in vivo effect of MDE-8 was studied in an Fc γRIIa 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 Fc γRIIa, induces modulation of both Fc γRIIa and Fc γRI from phagocytic cells, and ameliorates antibody-induced anaemia in vivo. [ABSTRACT FROM AUTHOR]