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

Br J Haematol. 2005 Jul;130(1):130-7. 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 (FcgammaRIIa) molecules on CD32 transfectants, peripheral blood monocytes, polymorphonuclear cells and platelets. This antibody blocked FcgammaRIIa 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 FcgammaRIIa. MDE-8 whole antibody induced a concomitant c. 30% decrease of FcgammaRI on THP-1 cells and monocytes. In humans FcgammaRIIa plays an important role in the clearance of antibody-coated red blood cells in vivo. As an equivalent of FcgammaRIIa does not exist in mice, the in vivo effect of MDE-8 was studied in an FcgammaRIIa 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 FcgammaRIIa, induces modulation of both FcgammaRIIa and FcgammaRI from phagocytic cells, and ameliorates antibody-induced anaemia in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anemia, Hemolytic, Autoimmune / genetics
  • Anemia, Hemolytic, Autoimmune / immunology
  • Anemia, Hemolytic, Autoimmune / prevention & control*
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antigens, CD / genetics*
  • Antigens, CD / immunology
  • Cells, Cultured
  • Granulocytes / pathology
  • Humans
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • Phagocytosis
  • Platelet Activation
  • Receptors, IgG / genetics
  • Receptors, IgG / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Fc gamma receptor IIA
  • Receptors, IgG