Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia.

Authors: Teeling, JL  Jansen-Hendriks, T  Kuijpers, TW  De Haas, M  Van De Winkel, JG  Hack, CE  Bleeker, WK 
Citation: Teeling JL, etal., Blood. 2001 Aug 15;98(4):1095-9.
Pubmed: (View Article at PubMed) PMID:11493456

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 gamma 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 alpha(IIb)beta(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-Fc gamma RII/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 gamma-chain, lacking Fc gamma RI, Fc gamma RIII, and Fc gamma RIII(-/-) mice. Infusion of a single dose of IVIG with a high IgG dimer content on the 4th day--ie, mimicking therapeutic administration--resulted 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 gamma 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. (Blood. 2001;98:1095-1099)

Annotation

Disease Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 2316362
Created: 2010-02-09
Species: All species
Last Modified: 2010-02-09
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.