Mechanistic properties of intravenous immunoglobulin in murine immune thrombocytopenia: support for FcγRIIB falls by the wayside.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterised by platelet clearance resulting from the production of platelet-reactive autoantibodies. Platelet clearance appears to occur mainly via phagocytosis in the mononuclear phagocytic system, although T-cell-mediated platelet destruction, platelet apoptosis and dysregulation of platelet production can also play a role in disease pathogenesis. One of the most successful treatments for ITP is intravenous immunoglobulin (IVIg), and while it has been used in ITP for over 30 years, its mechanism(s) of action still remain unclear. Animal models of ITP have proven useful in understanding IVIg's immunomodulatory properties, providing a valuable tool to test new mechanistic theories as well as further explore the soundness of older ones. This model has also provided the key evidence that IVIg exerts its effects via activating receptors for IgG Fc, specifically FcγRIII, via formation of IgG dimers or immune complexes. Here, we discuss the validity of one prominent theory of IVIg function, anti-inflammatory activity mediated through the inhibitory Fcγ receptor FcγRIIB, and review evidence to suggest that this theory is not likely valid in the practical sense.