Monoclonal antibodies that mimic the action of anti-D in the amelioration of murine ITP act by a mechanism distinct from that of IVIg
- 15 February 2005
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 105 (4), 1546-1548
- https://doi.org/10.1182/blood-2004-05-1886
Abstract
The mechanism of action of intravenous immunoglobulin (IVIg) and polyclonal anti-D–mediated reversal of immune thrombocytopenia (ITP) is still unclear. However, in a murine model of ITP, the therapeutic effect of IVIg appears to be wholly dependent upon the expression of the inhibitory Fc receptor, FcγRIIB. We previously demonstrated that, similar to anti-D in humans, 2 erythrocyte-reactive monoclonal antibodies (TER119 and M1/69) ameliorated murine ITP and inhibited reticuloendothelial system (RES) function at doses that protected against thrombocytopenia. The current study evaluated the involvement of the inhibitory and activating Fc receptors, FcγRIIB and FcγRIIIA, respectively, in the TER119 and M1/69-mediated inhibition of thrombocytopenia. In contrast to IVIg, in FcγRIIB-deficient mice, both monoclonal antibodies ameliorated ITP and both significantly down-regulated the level of expression of the activating FcγRIIIA in splenic macrophages. These results indicate that anti-erythrocyte antibodies that ameliorate ITP act independently of FcγRIIB expression but are dependent upon the activating FcγRIIIA.Keywords
This publication has 20 references indexed in Scilit:
- Intravenous (IV) anti‐D and IV immunoglobulin achieve acute platelet increases by different mechanisms: modulation of cytokine and platelet responses to IV anti‐D by FcγRIIa and FcγRIIIa polymorphismsBritish Journal of Haematology, 2004
- Role of Fc?? Receptors in the Pathogenesis and Treatment of Idiopathic Thrombocytopenic PurpuraJournal of Pediatric Hematology/Oncology, 2003
- Anti-D initially stimulates an Fc-dependent leukocyte oxidative burst and subsequently suppresses erythrophagocytosis via interleukin-1 receptor antagonistBlood, 2003
- IVIg-mediated amelioration of murine ITP via FcγRIIB is independent of SHIP1, SHP-1, and Btk activityBlood, 2003
- Enhanced Efficacy of Anti-D Immunoglobulin for Treating ITP is not Explained by Higher Immunoglobulin Polymer ContentBiologicals, 2001
- Anti-inflammatory Activity of IVIG Mediated Through the Inhibitory Fc ReceptorScience, 2001
- Treatment of Refractory Immune Thrombocytopenic Purpura with an Anti-Fcγ-Receptor AntibodyNew England Journal of Medicine, 1986
- EFFECT OF INTRAVENOUS IMMUNOGLOBULIN IN IMMUNE THROMBOCYTOPENIA: Competitive Inhibition of Reticuloendothelial System Function by Sequestration of Autologous Red Blood Cells?The Lancet, 1983
- Transient Reversal of Thrombocytopenia in Idiopathic Thrombocytopenic Purpura by High-Dose Intravenous Gamma GlobulinNew England Journal of Medicine, 1982
- Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors.The Journal of Experimental Medicine, 1979