A novel human CD32 mAb blocks experimental immune haemolytic anaemia in FcgammaRIIA transgenic mice.
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.
Immunotherapy Laboratory, Department of Immunology, University Medical Centre Utrecht, the Netherlands.
Annet
A
van Royen-Kerkhof
Elisabeth A M
EA
Sanders
Vanessa
V
Walraven
Marleen
M
Voorhorst-Ogink
Eirikur
E
Saeland
Jessica L
JL
Teeling
Arnout
A
Gerritsen
Marc A
MA
van Dijk
Wietse
W
Kuis
Ger T
GT
Rijkers
Laura
L
Vitale
Tibor
T
Keler
Steven E
SE
McKenzie
Jeanette H W
JH
Leusen
Jan G J
JG
van de Winkel
D000744:Anemia, Hemolytic, Autoimmune / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D006098:Granulocytes / Q000473:pathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D010587:Phagocytosis; D015539:Platelet Activation; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG