Human Rho(D) immune globulin

The mechanism of action of therapy is unclear. It is suggested that Rho immune globulin predominantly prevents the antibody response during incompatible pregnancy by accelerating the phagocytosis of RBC's and clearance from the circulation before the recognition by the immune system. IgG-opsonized RBCs may interact with activating IgG receptors (FcγRs) on effector cells and elicit phagocytosis via mononuclear phagocytic system, primarily by macrophages. IgG may also stimulate complement activation on the RBC surface, followed by RBC lysis or complement receptor-mediated phagocytosis but to smaller extent. Rho-specific IgG may inhibit the late stages of B cell activation by being internalized with Rho antigen by B cells, which alters the antigen processing and presentation. In response to the IgG-antigen complex formation, the immune globulin enhances the presentation of specific peptides and proliferation of epitope-specific T cells. Therapeutic efficacy of Rho (D) immune globulin in chronic immune thrombocytopenic purpura (ITP) may be explained by FcR blockade as well as the increase in the platelet count by substituting antibody-coated RBCs for antibodycoated platelets. In vitro studies of cytokine expression in human monocytes and granulocytes exposed to anti-D coated red blood cells have demonstrated enhanced secretion of interleukin 1 receptor antagonist resulting in down-regulation of FcγR mediated phagocytosis. Murine models show that RBC-specific antibodies can increase platelet counts by down-regulating FcγRIIIa on splenic macrophage, which is an opposing effect as predicted in intravenous Rho IgG.