The effect of monoclonal anti-human-platelet antibodies on platelet kinetics in a baboon model: IgG subclass dependency.
We assessed the in vivo effect of six intact anti-human antiplatelet antibodies of two major IgG subclasses on platelet kinetics in baboons. Five of the six antibodies tested caused thrombocytopenia of varying degree when injected at a precalculated threshold value. An agglutinating IgG1 antibody (MA-8L4A12) caused a long-lasting, mild thrombocytopenia with a predominant uptake of radiolabelled platelets in the spleen, while the four IgG2 antibodies tested (MA-13G8E1, MA-2M5A6, MA-21K2E8 and MA-22M10) caused a severe, transient thrombocytopenia with uptake of platelets in the liver. Two of the IgG2 antibodies (MA-13G8E1 and MA-2M5A6) caused platelet activation and aggregation in vitro, whilst the other two did not elicit a platelet aggregation response. The platelet survival time was shortened with all five of the thrombocytopenia-inducing antibodies, while only one antibody (MA-2M5A6) had a significant effect on the bleeding time. This study indicates that the IgG subclasss may be a determining factor in the outcome of platelet sequestration in immune-induced thrombocytopenia.
Coetzee
L M
LM
Department of Haematology and Cell Biology, University of the Orange Free State, Bloemfontein, South Africa. gnhmlmc@med.uovs.ac.za
Pieters
H
H
van Wyk
V
V
Cooper
S
S
Roodt
J
J
De Reys
S
S
Badenhorst
P N
PN
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D017099:IgG Deficiency; D010215:Papio; D015539:Platelet Activation; D013921:Thrombocytopenia / Q000276:immunology*
D000906:Antibodies