Royen-Kerkhof, A., Sanders, E.A.M., Walraven, V., Voorhorst-Ogink, M., Saeland, E., Teeling, J.L., Gerritsen, A., Dijk, M.A., Kuis, W., Rijkers, G.T., Vitale, L., Keler, T., McKenzie, S.E., Leusen, J.H.W. and Winkel, J.G.J. (2005) A novel human CD32 mAb blocks experimental immune haemolytic anaemia in Fc gamma RIIA transgenic mice. British Journal of Haematology, 130 (1), 130-137. (doi:10.1111/j.1365-2141.2005.05571.x).
Abstract
A fully human IgG1 kappa antibody (MDE-8) was generated, which recognised Fc-gamma receptor IIa (Fc?RIIa) molecules on CD32 transfectants, peripheral blood monocytes, polymorphonuclear cells and platelets. This antibody blocked Fc?RIIa 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?RIIa. MDE-8 whole antibody induced a concomitant c. 30% decrease of Fc?RI on THP-1 cells and monocytes. In humans Fc?RIIa plays an important role in the clearance of antibody-coated red blood cells in vivo. As an equivalent of Fc?RIIa does not exist in mice, the in vivo effect of MDE-8 was studied in an Fc?RIIa 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?RIIa, induces modulation of both Fc?RIIa and Fc?RI from phagocytic cells, and ameliorates antibody-induced anaemia in vivo.
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