Mechanisms of immune regulation by IVIG

PURPOSE OF REVIEW: In the past few years there have been many advances in our understanding of the mechanisms by which intravenous immune globulin (IVIG) modulates immune function in autoimmune disorders. RECENT FINDINGS: Previous investigations have focused on the Fc domain of the IgG molecule, and the role of the FcγRIIB receptor and the sialylated Fc domain that have been show to mediate the anti-inflammatory effects in certain murine models of autoantibody-mediated diseases. More recent findings have implicated the F(ab')₂ domain in IVIG-induced immune modulation in T-cell-mediated autoimmune disease models in which upregulation of T-regulatory cells and downregulation of the Th17 pathways are important components of this mechanism. The prostaglandin E pathway may be playing a role in the IVIG-induced changes in the T-regulatory pathway. SUMMARY: Many of the mechanisms proposed for the immune-modulating effects of IVIG demonstrate the complexity of immune effector functions in disease processes. Although controversy exists on the role of the FcγRIIB receptor and the importance of the sialylated Fc domain in human autoimmune disorders, probably no one single mechanism is responsible for the effects of IVIG in autoimmune and inflammatory diseases. The potential role of the prostaglandin E pathway may offer alternative treatments.