Therapeutic efficacy of intravenous immunoglobulin preparations depends onthe immunoglobulin G dimers: studies in experimental immune thrombocytopenia

The clinical benefit of intravenous immunoglobulin (IVIG) preparations in t he treatment of immune thrombocytopenic purpura (ITP) is supposed to be med iated by blockade of Fc gamma receptor-bearing phagocytes. In 2 experimenta l models for ITP, it is shown that the therapeutic efficacy of IVIG prepara tions is related to the IgG dimer content present in these preparations. A rat monoclonal antibody (mAb; MWReg30) directed to the murine platelet-spec ific integrin alpha (IIb)beta (3) (gpIIb/IIIa) was administered intraperito neally either as bolus injection or continuous infusion. With bolus injecti on, the circulating platelet count dropped to almost zero within 3 hours. P retreatment with cobra venom factor did not affect platelet depletion, wher eas pretreatment with anti-Fc gamma RII/III mAb 2.4G2 or IVIG greatly reduc ed platelet clearance. With continuous infusion, platelet numbers reached a steady state after 4 days, at approximately 25% of control. This reduction in platelets was, however, not observed in mice deficient for the FcR gamm a -chain, lacking Fc gamma RI, Fc-gamma RIII, and Fc gamma RIII-/- mice. In fusion of a single dose of IVIG with a high IgG dimer content on the 4th da y-ie, mimicking therapeutic administration-resulted in a platelet increase for several days. IVIG predominantly consisting of monomeric IgG had no eff ect on platelet numbers. In conclusion, continuous infusion of MWReg30 indu ces thrombocytopenia in mice by enhancing Fc gamma receptor-mediated cleara nce of platelets. In this model, it is shown that IgG dimers present in IVI G preparations are responsible for the increase in platelet counts. (C) 200 1 by The American Society of Hematology.