Monoclonal IgG can ameliorate immune thrombocytopenia in a murine model of ITP: an alternative to IVIG.
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.
Song
Seng
S
Transfusion Medicine Research and the Department of Laboratory Medicine and Pathobiology, St Michael's Hospital, Toronto, ON, Canada.
Crow
Andrew R
AR
Freedman
John
J
Lazarus
Alan H
AH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology*; D001327:Autoimmune Diseases / Q000517:prevention & control / Q000628:therapy*; D001792:Blood Platelets / Q000276:immunology; D051927:CD24 Antigen; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D005856:Germ-Free Life; D018960:Hyaluronan Receptors / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007518:Isoantibodies / Q000633:toxicity; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D012157:Mononuclear Phagocyte System / Q000187:drug effects / Q000276:immunology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000517:prevention & control / Q000628:therapy*; D017452:Receptors, IgG / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D018960:Hyaluronan Receptors; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D008562:Membrane Glycoproteins; D017452:Receptors, IgG