The immunomodulatory effects of intravenous immunoglobulin therapy in Kawasaki disease

Abstract

The introduction of intravenous immunoglobulin (IVIG) for modulation of inflammation in acute Kawasaki disease was a great therapeutic triumph. However, three decades later, the mechanisms underlying immune regulation by IVIG are only beginning to be revealed. Stimulation of an immature myeloid population of dendritic cells that secretes IL-10 and the elucidation of Fc-specific natural regulatory T cells provide insights into the mechanisms of IVIG. Other potential mechanisms include provision of agent-specific neutralizing antibody, anti-idiotype and anti-cytokine antibodies, blockade of activating Fcγ receptors and stimulation of the inhibitory FcγRIIb receptor. New initiatives must seek to understand the mechanisms of IVIG in order to replace it one day with more affordable and more targeted therapies.

Keywords: Kawasaki disease; acquired heart disease; coronary artery aneurysms; immune regulation; myocardial infarction; pediatric vasculitis.

Figure 1

CD4+ CD25^high nTreg rapidly expand when peripheral blood mononuclear cells derived from a sub-acute KD patient after IVIG are stimulated in vitro for four days with Fc peptide sequences 121–135 and 126–140. Reproduced with permission from Informa Healthcare [46].