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A novel human CD32 mAb blocks experimental immune haemolytic anaemia in Fc γ RIIA transgenic mice
Author(s) -
RoyenKerkhof Annet,
Sanders Elisabeth A. M.,
Walraven Vanessa,
VoorhorstOgink Marleen,
Saeland Eirikur,
Teeling Jessica L.,
Gerritsen Arnout,
Dijk Marc A.,
Kuis Wietse,
Rijkers Ger T.,
Vitale Laura,
Keler Tibor,
McKenzie Steven E.,
Leusen Jeanette H. W.,
Winkel Jan G. J.
Publication year - 2005
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05571.x
Subject(s) - antibody , in vivo , fc receptor , monoclonal antibody , genetically modified mouse , immune system , immunology , transgene , receptor , microbiology and biotechnology , in vitro , chemistry , biology , biochemistry , gene
Summary A fully human IgG1 kappa antibody (MDE‐8) was generated, which recognised Fc‐gamma receptor IIa (Fc γ RIIa) molecules on CD32 transfectants, peripheral blood monocytes, polymorphonuclear cells and platelets. This antibody blocked Fc γ 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 γ RIIa. MDE‐8 whole antibody induced a concomitant c. 30% decrease of Fc γ RI on THP‐1 cells and monocytes. In humans Fc γ RIIa plays an important role in the clearance of antibody‐coated red blood cells in vivo . As an equivalent of Fc γ RIIa does not exist in mice, the in vivo effect of MDE‐8 was studied in an Fc γ 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 γ RIIa, induces modulation of both Fc γ RIIa and Fc γ RI from phagocytic cells, and ameliorates antibody‐induced anaemia in vivo .