Can IVIg Preparations with Specificity for Soluble Antigens Mimic the Therapeutic Effects of IVIg in the Treatment of Immune Thrombocytopenia?.

Abstract

Intravenous immunoglobulin (IVIg) mediates protection from the effects of immune thrombocytopenic purpura (ITP). In addition, an IVIg specific for a cell-associated antigen (anti-D) is also able to increase platelet counts in D positive subjects with ITP. Whether an IVIg directed to a soluble antigen can likewise be beneficial in ITP is, however, unknown. A murine model of ITP was used to determine the effectiveness of IgG specific to soluble antigens in treating immune thrombocytopenia. Ovalbumin (OVA) was selected as the primary target antigen because it can be used in its soluble form or can be coupled to syngeneic red blood cells (OVA-RBC), and the same anti-OVA antibody could be used with both OVA and OVA-RBC. Mice were injected with either preformed soluble OVA + anti-OVA, OVA-RBC's presensitised with anti-OVA, or appropriate control preparations, followed by an anti-platelet antibody to induce thrombocytopenia. Both experimental regimes, but none of the control preparations, protected mice from ITP. Similar to IVIg, soluble OVA + anti-OVA did not have any effect on thrombocytopenia in mice lacking the inhibitory receptor FcγRIIB (FcγRIIB−/−). In contrast, injection of anti-OVA sensitised OVA-RBC's did ameliorate thrombocytopenia in FcγRIIB−/− mice. Finally, mice injected with IgG specific for the endogenous soluble antigens, albumin and transferrin, also inhibited ITP in an FcγRIIB-dependent manner. We conclude that IgG antibodies directed to soluble antigens can inhibit or reverse immune thrombocytopenia in an FcγRIIB-dependent manner.