Mechanisms of intravenous immunoglobulin action in immune thrombocytopenic purpura

The use of high-dose intravenous gamma immunoglobulin (IVIG) for the treatment of immune thrombocytopenic purpura (ITP) was first reported more than two decades ago. After the therapeutic benefit of IVIG was established in ITP, it was then successfully used to treat many other autoimmune diseases. Although a complete definition of the mechanism of IVIG action is still lacking, extensive research suggests that IVIG may achieve its therapeutic effects through multiple mechanisms. IVIG exerts immunomodulatory effects that may include antiidiotypic neutralization of antiplatelet antibodies, stimulation of Fcγ receptor IIB expression, and inhibition of Fcγ receptor-mediated platelet destruction. Recent work suggests that a large fraction of the benefit provided by IVIG may be the result of competitive inhibition of neonatal Fc receptor (FcRn) and IVIG-induced acceleration of antiplatelet antibody elimination. This review provides an overview and critical discussion of mechanisms that may be responsible of IVIG effects in ITP.