Intravenous immunoglobulin (IVIG) is prepared from large pools of plasma from healthy donors and is widely used to treat autoimmune diseases, especially immune thrombocytopenic purpura (ITP). Human polyclonal antierythrocyte antibodies, such as anti-D, can also be effective at treating ITP in individuals expressing the appropriate antigen. The demand for IVIG and anti-D exceeds the supply, and the development of a recombinant product to replace these human-derived blood products would be highly desirable. We have hypothesized that monoclonal antibodies directed against red cells may be effective in inhibiting immune forms of thrombocytopenia.
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 (CD24) found on erythrocytes. After 24 hours, the mice were treated with antiplatelet (anti-GPIIb) antibody. Thrombocytopenia was assessed after a further 24 hours by flow cytometry. Standard human IVIG prevented thrombocytopenia, as expected. The monoclonal antibody specific for the TER-119 antigen and one of the anti-CD24-specific antibodies inhibited thrombocytopenia almost as well as IVIG at a 1,000× lower dose than IVIG. The antibodies that did inhibit thrombocytopenia significantly blocked reticuloendothelial system (RES) function but not the anti-CD24 antibody, which did not inhibit thrombocytopenia.
To determine if a monoclonal antibody that blocks RES function (anti-FcgR) vs those that bind/block complement receptors could also inhibit thrombocytopenia, we examined the effect of an antibody to FcgRII/III (2.4G2) as well as two antibodies directed to complement receptors 1, 2, and 3. Only the blocking anti-FcgRII/III antibody, but neither of the antibodies specific for the complement receptors, inhibited thrombocytopenia.
CONCLUSION: It is proposed that IVIG and/or polyclonal anti-D could be replaced by monoclonal antibodies directed to red cells in the treatment of ITP.
Click here to read Dr. Bruce Cheson's commentary on this abstract.
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