Monoclonal IgG can ameliorate immune thrombocytopenia in a murine model of ITP: an alternative to IVIG

Abstract

Intravenous immunoglobulin (IVIG) is used to treat immune thrombocytopenia resulting from a variety of autoimmune and nonautoimmune diseases such as idiopathic thrombocytopenic purpura (ITP), heparin-induced thrombocytopenia, and posttransfusion purpura. IVIG is a limited resource and although considered safe, may nevertheless carry some risk of transferring disease. Its high cost makes monoclonal antibodies, capable of mimicking the clinical effects of IVIG, highly desirable. We show here, using a murine model of ITP, that selected monoclonal antibodies can protect against thrombocytopenia. SCID mice were pretreated with 1 of 21 monoclonal antibodies before induction of thrombocytopenia by antiplatelet antibody. Four antibodies reacted with the CD24 antigen on erythrocytes. Two antibodies were of the IgM class, and although one IgM antibody caused a minimal degree of anemia (P <.05), neither antibody ameliorated immune thrombocytopenia. One of 2 anti-CD24 antibodies of the IgG class ameliorated immune thrombocytopenia and blocked reticuloendothelial system function at the same doses that protected against thrombocytopenia. Some antibodies reactive with other circulating cell types also protected against immune-mediated thrombocytopenia while no antibody without a distinct target antigen in the mice was protective. Protective monoclonal antibodies significantly prevented thrombocytopenia at down to a 1000-fold lower dose (200 microg/kg) as compared with standard IVIG treatment (2 g/kg). It is concluded that monoclonal IgG with specificity for a circulating cellular target antigen may provide an alternative therapeutic approach to treating immune thrombocytopenia.

Comparison of the effects of antibody-coated liposomes, IVIG, and anti-RBC immunotherapy in a murine model of passive chronic immune thrombocytopenia

“…Following 4 days of infusion, significant thrombocytopenia was achieved as platelet counts had dropped to approximately 30% of initial values (Figure 1), and all animals demonstrated petechiae. In comparison to our earlier work using a rat model of an antiplatelet antibody (7E3)-induced thrombocytopenia, 11,18,20 and in comparison with animal models presented by other groups, 21,22 the present model provides several advantages. For example, in contrast to other passive models where antiplatelet antibody was administered by intravenous or intraperitoneal injection, we have used osmotic pumps to deliver antiplatelet antibody via constant-rate infusion.…”

Rituximab-CD20 Complexes Are Shaved from Z138 Mantle Cell Lymphoma Cells in Intravenous and Subcutaneous SCID Mouse Models

“…injections of 300 g of mAb 2.4G2 or its fragments, given each morning, and RTX 6 h later. Human intravenous Ig (IVIG; Baxter) was administered to mice (50 mg i.p (36)) in the morning of days 1 and 3 and RTX 6 h later on 4 consecutive days.…”

Rapid irreversible encephalopathy associated with anti‐D immune globulin treatment for idiopathic thrombocytopenic purpura

“…On evaluation, the patient was found to have platelet count of 27 Â 10 3 /mm 3 and hemoglobin of 15 g/dL. The patient was subsequently diagnosed with ITP.…”

“…Over the next 5 weeks, the patient was treated with prednisone 80 mg QD followed by danazol 400 mg QD and a prednisone taper without sustained increase in the platelet count. IV RhIG therapy for refractory ITP was started for a platelet count of 10 Â 10 3 /mm 3 . The patient was D antigen positive.…”

“…The mechanism of IV RhIG function is likely related to sequestration of antibody-sensitized red cells. In an animal model of ITP, administration of anti-CD24 IgG antibodies ameliorates immune thrombocytopenia and blocks reticuloendothelial system function [3]. In humans, IV RhIG is shown in to increase platelet counts to greater than 20 Â 10 3 /mL 2 in over 70% of D positive nonsplenectomized patients [4].…”