Dynamics of immunocyte activation during intravenous immunoglobulin treatment in Kawasaki disease

Abstract

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.

Acknowledgements

We sincerely thank Ms Midori Wakabayashi-Takahara and Ms Yoko Mori (Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan) for technical assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supporting Information

Additional Supporting Information may be found in the online version of this article.

Supplementary table S1. Clinical features and laboratory findings of children with KD and healthy controls.Supplementary table S2. Clinical features and laboratory findings of male and female KD children before initial IVIG.

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