Abstract
Immune thrombocytopenia (ITP) is an autoimmune disease that is mediated by anti-platelet antibodies. It is believed that anti-platelet antibody-opsonized platelets are eliminated through Fcγ receptor-mediated and complement-mediated phagocytosis by macrophages of the reticuloendothelial system (RES). Polyclonal pooled immunoglobulin with high titer for the D-antigen of erythrocytes (i.e., anti-D) has been successfully used to ameliorate ITP. Based on the pathogenesis of ITP and based on the successful application of anti-D for the treatment of ITP, we hypothesized that antibody-coated liposomes may be used to inhibit Fcγ receptor-mediated and complement-mediated phagocytosis, thereby increasing platelet counts in ITP. To test this hypothesis, we have developed a liposome preparation that is coated with a model monoclonal IgG1 antibody. Antibody-coated liposomes were found to inhibit complement deposition and macrophage phagocytosis in vitro. Furthermore, antibody-coated liposomes were also found to attenuate thrombocytopenia in a rat model of ITP, in a dose-dependent manner. The results suggest that antibody-coated liposomes may be used as ‘decoy particles’ to competitively inhibit the destruction of antibody-coated platelets; thus, antibody-coated liposomes may have value in the treatment of ITP.
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