TORONTO—Monoclonal antibodies directed against red blood cells can be used to inhibit immune forms of thrombocytopenia, according to the results of studies with mice. These results were reported by Alan H. Lazarus, PhD, assistant professor of medicine, Department of Hematology, St. Michael’s Hospital, University of Toronto.
Currently, intravenous immuoglobulin (IVIG) prepared from large pools of healthy donors is widely used to treat autoimmune diseases, especially immune thrombocytopenic purpura (ITP). Human polyclonal antierythrocyte antibodies, such as anti-D, can also be effective in treating ITP in individuals expressing the appropriate antigen. The demand for IVIG and anti-D, however, exceeds the supply. The development of a recombinant product mimicking the action of these human-derived blood products could help meet the demand.
Competing Complex
"We know that ITP is an immune-mediated disease where you have platelets that are bound by a pathologic autoantibody. This platelet-antibody complex binds to complement receptor monocytes in the spleen and causes clearance of platelets." One of the proposed theories on how the human-derived blood products work to ameliorate ITP is that IVIG or anti-D binds to an antigen in the host (most likely a red cell in the case of anti-D) to form an immune complex that becomes a competitor with the platelet complex to bind to the receptor.
"If this is true," Dr. Lazarus said, "there is no reason why a monoclonal antibody binding to, for example, a red cell or some other antigen should not be able to reverse or prevent thrombocytopenia." He cautioned, however, that some monoclonal antibodies may be shown to work while others may not.
Works With Lower Dose
Mice were individually injected with 50 mg of human IVIG (2 g IVIG/kg body weight) vs 50 µg, 5 µg, or 0.5 µg of an antibody specific for the TER-119 erythrocyte antigen as well as two antibodies against the heat-stable antigen CD-24 found on erythrocytes. After 24 hours, the mice were treated with antiplatelet (anti-GPIIb) antibody.
