Anti-inflammatory Activity of IVIG Mediated Through the Inhibitory Fc Receptor

TLDR

The study examined the molecular basis of IVIG’s anti‑inflammatory effect in a murine immune thrombocytopenia model. Using wild‑type and Fcγ receptor–humanized mice, the authors assessed the role of FcγRIIB by administering intact IVIG or monomeric Fc fragments and manipulating the receptor genetically or with blocking antibodies. IVIG or Fc fragments prevented platelet consumption, required FcγRIIB, and upregulated its surface expression on splenic macrophages, demonstrating that enhancing inhibitory FcγRIIB signaling is a potent therapeutic strategy for autoantibody‑mediated inflammation.

Abstract

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.