The effect of monoclonal anti-human-platelet antibodies on platelet kinetics in a baboon model: IgG subclass dependency

We assessed the ill vivo effect of six intact anti-human antiplatelet antib odies of two major IgG subclasses on platelet kinetics in baboons. Five of the six antibodies tested caused thrombocytopenia of varying degree when in jected at a precalculated threshold value. An agglutinating IgG(1) antibody (MA-8L4A12) caused a long-lasting, mild thrombocytopenia with a predominan t uptake of radiolabelled platelets in the spleen, while the four IgG(2) an tibodies tested (MA-13G8E1, MA-2M5A6, MA-21K2E8 and MA-22M10) caused a seve re, transient thrombocytopenia with uptake of platelets in the liver. Two o f the IgG(2) antibodies (MA-13G8E1 and MA-2M5A6) caused platelet activation and aggregation in vitro, whilst the other two did nor elicit a platelet a ggregation response. The platelet survival time was shortened with all five of the thrombocytopenia-inducing antibodies, while only one antibody (MA-2 M5A6) had a significant effect on the bleeding time. This study indicates t hat the IgG subclasss may be a determining factor in the outcome of platele t sequestration in immune-induced thrombocytopenia.