Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor

A Samuelsson, TL Towers, JV Ravetch - Science, 2001 - science.org
A Samuelsson, TL Towers, JV Ravetch
Science, 2001science.org
The molecular basis for the anti-inflammatory property of intravenous gamma globulin (IVIG)
was investigated in a murine model of immune thrombocytopenia. Administration of clinically
protective doses of intact antibody or monomeric Fc fragments to wild-type or Fcγ receptor–
humanized mice prevented platelet consumption triggered by a pathogenic autoantibody.
The inhibitory Fc receptor, FcγRIIB, was required for protection, because disruption either by
genetic deletion or with a blocking monoclonal antibody reversed the therapeutic effect of …
The molecular basis for the anti-inflammatory property of intravenous gamma globulin (IVIG) was investigated in a murine model of immune thrombocytopenia. Administration of clinically protective doses of intact antibody or monomeric Fc fragments to wild-type or Fcγ receptor–humanized mice prevented platelet consumption triggered by a pathogenic autoantibody. The inhibitory Fc receptor, FcγRIIB, was required for protection, because disruption either by genetic deletion or with a blocking monoclonal antibody reversed the therapeutic effect of IVIG. Protection was associated with the ability of IVIG administration to induce surface expression of FcγRIIB on splenic macrophages. Modulation of inhibitory signaling is thus a potent therapeutic strategy for attenuating autoantibody-triggered inflammatory diseases.
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