Dynamics of immunocyte activation during intravenous immunoglobulin treatment in Kawasaki disease
Dynamics of immunocyte activation during intravenous immunoglobulin treatment in Kawasaki disease
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DOI：
10.1080/03009742.2019.1604992
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发表时间：
2019-07
影响因子：
2.1
通讯作者：
C. Matsuguma;H. Wakiguchi;Y. Suzuki;S. Okada;T. Furuta;Y. Ohnishi;Y. Azuma;S. Ohga;S. Hasegawa
中科院分区：
文献类型：
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作者：
C. Matsuguma;H. Wakiguchi;Y. Suzuki;S. Okada;T. Furuta;Y. Ohnishi;Y. Azuma;S. Ohga;S. Hasegawa
目的：川崎病（KawasakiDisease，KD）是一种发生于儿童早期的系统性血管炎.静脉注射免疫球蛋白（IVIG）是KD的标准治疗方法。然而，IVIG对大约15%的KD儿童无效，其机制尚不清楚。我们研究了IVIG有效和IVIG抵抗的KD患者IVIG治疗前后单核细胞和T细胞活化的变化。方法：我们分析了2011年1月至2016年5月期间入住山口大学医院的46名KD儿童的外周血CD 14 + CD 16+细胞和CD 4+和CD 8+细胞上的人类白细胞抗原DR（HLA-DR）表达。我们比较了IVIG有效组和IVIG抵抗组之间IVIG治疗前后CD 14 + CD 16+细胞、CD 4 +HLA-DR+细胞和CD 8 +HLA-DR+细胞绝对数的动力学。结果：46例患儿中IVIG有效型30例，IVIG抵抗型16例。IVIG有效组CD 14 + CD 16+细胞绝对数在IVIG治疗后明显下降，而IVIG抵抗组在IVIG治疗后CD 14 + CD 16+细胞绝对数无变化。IVIG后两组CD 4 +HLA-DR+细胞绝对数均显著增加。IVIG耐药组CD 8 +HLA-DR+细胞绝对数在IVIG前较低，IVIG后明显升高，而IVIG有效组在IVIG后CD 8 + HLA-DR+细胞绝对数无变化。结论：我们的研究结果表明，单核细胞抑制和T细胞活化的控制不足，特别是在CD 8相关的免疫系统方面，与IVIG抵抗有关。T细胞抑制的恢复对于KD恢复可能是重要的。这些发现为IVIG耐药机制提供了新的见解。
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.