Nature Medicine
- 12, 688 - 692 (2006)
Published online: 21 May 2006; | doi:10.1038/nm1416
Intravenous immunoglobulin ameliorates ITP via activating Fc receptors on dendritic cellsVinayakumar Siragam1, 2, 4, Andrew R Crow1, 2, 4, Davor Brinc1, 2, Seng Song2, John Freedman1, 2, 3 & Alan H Lazarus11
Canadian Blood Services, 1800 Alta Vista Drive, Ottawa, Ontario, K1G 4J5, Canada. 2
Transfusion Medicine Research, Department of Laboratory Medicine, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada. 3
Department of Medicine, University of Toronto, 190 Elizabeth Street, Toronto, Ontario M5G 2C4, and the Toronto Platelet Immunobiology Group, Toronto, Ontario, Canada. 4
These authors contributed equally to this work.
Correspondence should be addressed to Alan H Lazarus lazarusa@smh.toronto.on.ca Despite a more than 20-year experience of therapeutic benefit, the relevant molecular and cellular targets of intravenous immunoglobulin (IVIg) in autoimmune disease remain unclear. Contrary to the prevailing theories of IVIg action in autoimmunity, we show that IVIg drives signaling through activating Fc receptors (FcR) in the amelioration of mouse immune thrombocytopenic purpura (ITP). The actual administration of IVIg was unnecessary because as few as 105 IVIg-treated cells could, upon adoptive transfer, ameliorate ITP. IVIg did not interact with the inhibitory FcRIIB on the initiator cell, although FcRIIB does have a role in the late phase of IVIg action. Notably, only IVIg-treated CD11c
+ dendritic cells could mediate these effects. We hypothesize that IVIg forms soluble immune complexes in vivo that prime dendritic-cell regulatory activity. In conclusion, the clinical effects of IVIg in ameliorating ITP seem to involve the acute interaction of IVIg with activating FcR on dendritic cells.
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