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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-10-3078.
Submitted October 10, 2002
Accepted December 17, 2002
Monoclonal IgG can ameliorate immune thrombocytopenia in a murine model of ITP: an alternative to IVIG
Seng Song, Andrew R Crow, John Freedman, and Alan H Lazarus*
Transfusion Medicine Research, St Michael's Hospital, Toronto, ON, Canada
Canadian Blood Services, and Thr Toronto Platelet Immunobiology Group, Toronto, ON, Canada
* Corresponding author; email: lazarusa{at}smh.toronto.on.ca.
Intravenous immunoglobulin (IVIG) is used to treat immune thrombocytopenia resulting from a variety of autoimmune and non-autoimmune diseases such as idiopathic thrombocytopenic purpura (ITP), heparin-induced thrombocytopenia, and post-transfusion 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 one of 21 monoclonal antibodies before induction of thrombocytopenia by anti-platelet 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<0.05), neither antibody ameliorated immune thrombocytopenia. One of two anti-CD24 antibodies of the IgG class ameliorated immune thrombocytopenia, and blocked reticuloendothelial system function at the same doses which 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 4-log fold lower dose (200 µ/Kg) as compared to 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.
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