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Monoclonal Antibodies Mimic Action of IVIG and Can Inhibit Immune Thrombocytopenia

Monoclonal Antibodies Mimic Action of IVIG and Can Inhibit Immune Thrombocytopenia

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.

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