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A novel human CD32 mAb blocks experimental immune haemolytic anaemia in Fc gamma RIIA transgenic mice

A novel human CD32 mAb blocks experimental immune haemolytic anaemia in Fc gamma RIIA transgenic mice
A novel human CD32 mAb blocks experimental immune haemolytic anaemia in Fc gamma RIIA transgenic mice
A fully human IgG1 kappa antibody (MDE-8) was generated, which recognised Fc-gamma receptor IIa (Fc?RIIa) molecules on CD32 transfectants, peripheral blood monocytes, polymorphonuclear cells and platelets. This antibody blocked Fc?RIIa ligand-binding via its F(ab')2 fragment. Overnight incubation of monocytes with F(ab')2 fragments of MDE-8 leads to a c. 60% decrease in cell surface expression of Fc?RIIa. MDE-8 whole antibody induced a concomitant c. 30% decrease of Fc?RI on THP-1 cells and monocytes. In humans Fc?RIIa plays an important role in the clearance of antibody-coated red blood cells in vivo. As an equivalent of Fc?RIIa does not exist in mice, the in vivo effect of MDE-8 was studied in an Fc?RIIa transgenic mouse model. In these mice, antibody-induced anaemia could readily be blocked by MDE-8. These data document a new human antibody that effectively blocks Fc?RIIa, induces modulation of both Fc?RIIa and Fc?RI from phagocytic cells, and ameliorates antibody-induced anaemia in vivo.
fc receptors, antibodies, autoimmunity, transgenic mic
0007-1048
130-137
Royen-Kerkhof, A.
1ef454d0-d62f-498c-8963-03bddd8afbf0
Sanders, E.A.M.
bcbe3fdd-0369-4396-be94-1a03d58daed4
Walraven, V.
3c7ff729-638c-4036-b2b4-0c13a0ed74d1
Voorhorst-Ogink, M.
8a34f7dc-ca16-4014-95fd-6977a4f3e347
Saeland, E.
3ba56598-593c-457c-8687-0a65a376ee9d
Teeling, J.L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Gerritsen, A.
232ca49a-e2fe-4c12-924b-df56e4783230
Dijk, M.A.
0477c404-bf41-45d4-a66a-ad00dbd8dd43
Kuis, W.
60b4299c-b3d5-4726-8004-539d8fd5cc17
Rijkers, G.T.
c6e39a44-6f38-49a0-9d3e-1575b34982c9
Vitale, L.
b87ebbfb-bbd7-49b0-a22d-dfbc6548231f
Keler, T.
2ce68d06-4124-4fcf-aa53-0ee224d112d0
McKenzie, S.E.
693f7c4f-2d7a-481d-a860-cd07bc6c130a
Leusen, J.H.W.
54c18c11-9229-408e-bbac-a74d037a9f7e
Winkel, J.G.J.
559a39d9-4afe-4e0f-bf31-e930b072a182
Royen-Kerkhof, A.
1ef454d0-d62f-498c-8963-03bddd8afbf0
Sanders, E.A.M.
bcbe3fdd-0369-4396-be94-1a03d58daed4
Walraven, V.
3c7ff729-638c-4036-b2b4-0c13a0ed74d1
Voorhorst-Ogink, M.
8a34f7dc-ca16-4014-95fd-6977a4f3e347
Saeland, E.
3ba56598-593c-457c-8687-0a65a376ee9d
Teeling, J.L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Gerritsen, A.
232ca49a-e2fe-4c12-924b-df56e4783230
Dijk, M.A.
0477c404-bf41-45d4-a66a-ad00dbd8dd43
Kuis, W.
60b4299c-b3d5-4726-8004-539d8fd5cc17
Rijkers, G.T.
c6e39a44-6f38-49a0-9d3e-1575b34982c9
Vitale, L.
b87ebbfb-bbd7-49b0-a22d-dfbc6548231f
Keler, T.
2ce68d06-4124-4fcf-aa53-0ee224d112d0
McKenzie, S.E.
693f7c4f-2d7a-481d-a860-cd07bc6c130a
Leusen, J.H.W.
54c18c11-9229-408e-bbac-a74d037a9f7e
Winkel, J.G.J.
559a39d9-4afe-4e0f-bf31-e930b072a182

Royen-Kerkhof, A., Sanders, E.A.M., Walraven, V., Voorhorst-Ogink, M., Saeland, E., Teeling, J.L., Gerritsen, A., Dijk, M.A., Kuis, W., Rijkers, G.T., Vitale, L., Keler, T., McKenzie, S.E., Leusen, J.H.W. and Winkel, J.G.J. (2005) A novel human CD32 mAb blocks experimental immune haemolytic anaemia in Fc gamma RIIA transgenic mice. British Journal of Haematology, 130 (1), 130-137. (doi:10.1111/j.1365-2141.2005.05571.x).

Record type: Article

Abstract

A fully human IgG1 kappa antibody (MDE-8) was generated, which recognised Fc-gamma receptor IIa (Fc?RIIa) molecules on CD32 transfectants, peripheral blood monocytes, polymorphonuclear cells and platelets. This antibody blocked Fc?RIIa ligand-binding via its F(ab')2 fragment. Overnight incubation of monocytes with F(ab')2 fragments of MDE-8 leads to a c. 60% decrease in cell surface expression of Fc?RIIa. MDE-8 whole antibody induced a concomitant c. 30% decrease of Fc?RI on THP-1 cells and monocytes. In humans Fc?RIIa plays an important role in the clearance of antibody-coated red blood cells in vivo. As an equivalent of Fc?RIIa does not exist in mice, the in vivo effect of MDE-8 was studied in an Fc?RIIa transgenic mouse model. In these mice, antibody-induced anaemia could readily be blocked by MDE-8. These data document a new human antibody that effectively blocks Fc?RIIa, induces modulation of both Fc?RIIa and Fc?RI from phagocytic cells, and ameliorates antibody-induced anaemia in vivo.

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More information

Published date: 13 June 2005
Keywords: fc receptors, antibodies, autoimmunity, transgenic mic

Identifiers

Local EPrints ID: 55879
URI: https://eprints.soton.ac.uk/id/eprint/55879
ISSN: 0007-1048
PURE UUID: de0733be-313d-4177-93f0-8baa63fd8a57

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Date deposited: 06 Aug 2008
Last modified: 17 Jul 2017 14:31

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Contributors

Author: A. Royen-Kerkhof
Author: E.A.M. Sanders
Author: V. Walraven
Author: M. Voorhorst-Ogink
Author: E. Saeland
Author: J.L. Teeling
Author: A. Gerritsen
Author: M.A. Dijk
Author: W. Kuis
Author: G.T. Rijkers
Author: L. Vitale
Author: T. Keler
Author: S.E. McKenzie
Author: J.H.W. Leusen
Author: J.G.J. Winkel

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