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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1095-1099
IMMUNOBIOLOGY
Therapeutic efficacy of intravenous immunoglobulin preparations
depends on the immunoglobulin G dimers: studies in experimental immune
thrombocytopenia
Jessica L. Teeling,
Theo Jansen-Hendriks,
Taco W. Kuijpers,
Masja de Haas,
Jan G. J. van de Winkel,
C.
Erik Hack, and
Wim K. Bleeker
From the Central Laboratory of the Netherlands Red
Cross Blood Transfusion Service, the Laboratory of Experimental and
Clinical Immunology, and the Department of Pediatrics, Academical
Medical Center, University of Amsterdam; the Department of Clinical
Chemistry, Academical Hospital VU, Amsterdam; and the Department of
Immunology and Genmab, University Medical Center Utrecht, The
Netherlands.
The clinical benefit of intravenous immunoglobulin (IVIG)
preparations in the treatment of immune thrombocytopenic purpura (ITP)
is supposed to be mediated by blockade of Fc receptor-bearing phagocytes. In 2 experimental models for ITP, it is shown that the
therapeutic efficacy of IVIG preparations is related to the IgG dimer
content present in these preparations. A rat monoclonal antibody (mAb;
MWReg30) directed to the murine platelet-specific integrin
 IIb 3 (gpIIb/IIIa) was administered
intraperitoneally either as bolus injection or continuous infusion.
With bolus injection, the circulating platelet count dropped to almost
zero within 3 hours. Pretreatment with cobra venom factor did not
affect platelet depletion, whereas pretreatment with anti-FcRII/III
mAb 2.4G2 or IVIG greatly reduced platelet clearance. With continuous
infusion, platelet numbers reached a steady state after 4 days, at
approximately 25% of control. This reduction in platelets was,
however, not observed in mice deficient for the FcR-chain, lacking
FcRI, FcRIII, and FcRIII / mice. Infusion of a
single dose of IVIG with a high IgG dimer content on the 4th day ie,
mimicking therapeutic administrationresulted in a platelet
increase for several days. IVIG predominantly consisting of monomeric
IgG had no effect on platelet numbers. In conclusion, continuous
infusion of MWReg30 induces thrombocytopenia in mice by enhancing Fc
receptor-mediated clearance of platelets. In this model, it is shown
that IgG dimers present in IVIG preparations are responsible for the
increase in platelet counts.
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