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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-10-3078.
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Blood, 1 May 2003, Vol. 101, No. 9, pp. 3708-3713
TRANSFUSION MEDICINE
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
From Transfusion Medicine Research and the Department
of Laboratory Medicine and Pathobiology, St Michael's Hospital,
Toronto, ON; and the Canadian Blood Services and the Toronto Platelet
Immunobiology Group, ON, Canada.
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 µg/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.

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