Dynamics of immunocyte activation during intravenous immunoglobulin treatment in Kawasaki disease

Objectives: Kawasaki disease (KD) is a systemic vasculitis of early childhood. Intravenous immunoglobulin (IVIG) is the standard treatment for KD. However, IVIG is not effective in approximately 15% of children with KD, and the mechanisms for this are unclear. We investigated changes in monocyte and T-cell activation from pre- to post-IVIG in IVIG-effective and IVIG-resistant KD. Method: We analysed peripheral CD14(+)CD16(+) cells and human leucocyte antigen-DR (HLA-DR) expression on CD4(+) and CD8(+) cells in 46 children with KD who were admitted to Yamaguchi University Hospital between January 2011 and May 2016. We compared the kinetics in the absolute numbers of CD14(+)CD16(+) cells, CD4(+)HLA-DR+ cells, and CD8(+)HLA-DR+ cells before and after IVIG treatment between IVIG-effective and IVIG-resistant groups. Results: Among the 46 subjects, 30 had IVIG-effective KD and 16 had IVIG-resistant KD. The absolute number of CD14(+)CD16(+) cells in the IVIG-effective group decreased significantly after IVIG, while that in the IVIG-resistant group showed no change after IVIG. The absolute number of CD4(+)HLA-DR+ cells increased significantly after IVIG in both groups. The absolute number of CD8(+)HLA-DR+ cells before IVIG was low and significantly increased after IVIG in the IVIG-resistant group, while that in the IVIG-effective group showed no change after IVIG. Conclusions: Our results suggest that insufficient control of monocyte suppression and T-cell activation, especially in terms of the CD8-related immune system, are associated with IVIG resistance. The restoration of T-cell suppression may be important for KD recovery. These findings provide insight into the mechanism of IVIG resistance.