IVIg inhibits reticuloendothelial system function and ameliorates murine passive-immune thrombocytopenia independent of anti-idiotype reactivity.
Although the mechanism of action of intravenous immunoglobulin (IVIg) in treating antibody-dependent thrombocytopenia remains unclear, most studies have suggested that IVIg blocks the function of Fc receptors in the reticuloendothelial system (RES) and/or the protective effect may be due to the presence of variable region-reactive (anti-idiotype) antibodies within IVIg. We evaluated the effect of IVIg on platelet counts in a murine model of passively induced immune thrombocytopenia (PIT). Although IVIg was unable to neutralize the binding of two platelet-specific monoclonal antibodies to their target antigens either in vivo or in vitro, it was able to prevent PIT as well as ameliorate pre-established PIT mediated by these antibodies. IVIg adsorbed against the antibody used to induce thrombocytopenia or endogenous murine immunoglobulin also protected against PIT, indicating that antibodies with anti-idiotype activity present in IVIg are not necessary for its effective treatment of PIT. IVIg significantly blocked the ability of the RES to clear antibody-sensitized red blood cells. F(ab')2 fragments of IVIg, which are unable to block the RES but retain the idiotypic regions, were ineffective at protecting mice from PIT. Our data suggest that IVIg exerts its rapid effect by inhibiting RES function and that anti-idiotype interactions are not required.
Crow
A R
AR
Transfusion Medicine Research and the Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, Toronto, Canada.
Song
S
S
Semple
J W
JW
Freedman
J
J
Lazarus
A H
AH
D000327:Adsorption; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D012157:Mononuclear Phagocyte System / Q000276:immunology*; D010976:Platelet Count; D018709:Statistics, Nonparametric; D013921:Thrombocytopenia / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D016756:Immunoglobulins, Intravenous