Intravenous immunoglobulin ameliorates ITP via activating Fc gamma receptors on dendritic cells.
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 gamma receptors (Fc gammaR) in the amelioration of mouse immune thrombocytopenic purpura (ITP). The actual administration of IVIg was unnecessary because as few as 10(5) IVIg-treated cells could, upon adoptive transfer, ameliorate ITP. IVIg did not interact with the inhibitory Fc gammaRIIB on the initiator cell, although Fc gammaRIIB 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 Fc gammaR on dendritic cells.
Siragam
Vinayakumar
V
Canadian Blood Services, 1800 Alta Vista Drive, Ottawa, Ontario, K1G 4J5, Canada.
Crow
Andrew R
AR
Brinc
Davor
D
Song
Seng
S
Freedman
John
J
Lazarus
Alan H
AH
D019264:Adoptive Transfer; D000818:Animals; D039481:CD11b Antigen / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology / Q000628:therapy; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology
D039481:CD11b Antigen; D039521:CD11c Antigen; C499172:Fcgr2b protein, mouse; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG