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

Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia
Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia
The clinical benefit of intravenous immunoglobulin (IVIG) preparations in the treatment of immune thrombocytopenic purpura (ITP) is supposed to be mediated by blockade of Fcg 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 aIIbb3 (gpIIb/IIIa) was administered intraperitoneally either as bolus injection or continuous infusion. With bolus injection, the circulating platelet count dropped to almost zero within 3hours. Pretreatment with cobra venom factor did not affect platelet depletion, whereas pretreatment with anti-FcgRII/IIImAb 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 FcRg-chain, lacking FcgRI, FcgRIII,and FcgRIII2/2 mice. Infusion of a single dose of IVIG with a high IgG dimer contenton 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 Fcg 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)
0006-4971
1095-1099
Teeling, Jessica.L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Jansen-Hendriks, Theo
5f1bb17c-adf9-45d9-b7da-38b327d55f3b
Kuijpers, Taco.W.
75b2c80b-47f5-4415-ab2d-f398ffdafe59
Haas, Masja
e6843008-fb46-4412-a867-c7162d81b26a
Winkel, Jan.G.J.
b838d9bf-087e-46a3-b236-04771c47e7ce
Hack, C.Erik
f2a19948-e2ab-4747-962f-e6d46921a243
Bleeker, Wim.K.
11ce7c46-56b6-4e31-95fc-bbc02d96dd07
Teeling, Jessica.L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Jansen-Hendriks, Theo
5f1bb17c-adf9-45d9-b7da-38b327d55f3b
Kuijpers, Taco.W.
75b2c80b-47f5-4415-ab2d-f398ffdafe59
Haas, Masja
e6843008-fb46-4412-a867-c7162d81b26a
Winkel, Jan.G.J.
b838d9bf-087e-46a3-b236-04771c47e7ce
Hack, C.Erik
f2a19948-e2ab-4747-962f-e6d46921a243
Bleeker, Wim.K.
11ce7c46-56b6-4e31-95fc-bbc02d96dd07

Teeling, Jessica.L., Jansen-Hendriks, Theo, Kuijpers, Taco.W., Haas, Masja, Winkel, Jan.G.J., Hack, C.Erik and Bleeker, Wim.K. (2001) Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia. Blood, 98 (4), 1095-1099. (doi:10.1182/blood.V98.4.1095).

Record type: Article

Abstract

The clinical benefit of intravenous immunoglobulin (IVIG) preparations in the treatment of immune thrombocytopenic purpura (ITP) is supposed to be mediated by blockade of Fcg 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 aIIbb3 (gpIIb/IIIa) was administered intraperitoneally either as bolus injection or continuous infusion. With bolus injection, the circulating platelet count dropped to almost zero within 3hours. Pretreatment with cobra venom factor did not affect platelet depletion, whereas pretreatment with anti-FcgRII/IIImAb 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 FcRg-chain, lacking FcgRI, FcgRIII,and FcgRIII2/2 mice. Infusion of a single dose of IVIG with a high IgG dimer contenton 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 Fcg 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)

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Published date: 15 August 2001

Identifiers

Local EPrints ID: 56285
URI: http://eprints.soton.ac.uk/id/eprint/56285
ISSN: 0006-4971
PURE UUID: 79d854c2-896f-4f10-900a-a97dab8e4baa
ORCID for Jessica.L. Teeling: ORCID iD orcid.org/0000-0003-4004-7391

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Date deposited: 07 Aug 2008
Last modified: 16 Mar 2024 03:41

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Contributors

Author: Theo Jansen-Hendriks
Author: Taco.W. Kuijpers
Author: Masja Haas
Author: Jan.G.J. Winkel
Author: C.Erik Hack
Author: Wim.K. Bleeker

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