Monoclonal antibodies that mimic the action of anti-D in the amelioration of murine ITP act by a mechanism distinct from that of IVIg.
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, Fc gamma RIIB. 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, Fc gamma RIIB and Fc gamma RIIIA, respectively, in the TER119 and M1/69-mediated inhibition of thrombocytopenia. In contrast to IVIg, in Fc gamma RIIB-deficient mice, both monoclonal antibodies ameliorated ITP and both significantly down-regulated the level of expression of the activating Fc gamma RIIIA in splenic macrophages. These results indicate that anti-erythrocyte antibodies that ameliorate ITP act independently of Fc gamma RIIB expression but are dependent upon the activating Fc gamma RIIIA.
Song
Seng
S
Transfusion Medicine Research, St Michael's Hospital, 30 Bond St, Toronto, ON, Canada M5B 1W8.
Crow
Andrew R
AR
Siragam
Vinayakumar
V
Freedman
John
J
Lazarus
Alan H
AH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007518:Isoantibodies / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D012204:Rh-Hr Blood-Group System / Q000276:immunology*; D018029:Rho(D) Immune Globulin
D000911:Antibodies, Monoclonal; C499172:Fcgr2b protein, mouse; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; C061961:RHO(D) antibody; D017452:Receptors, IgG; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin