Lack of CD4+CD25+FOXP3+ regulatory T cells is associated with resistance to intravenous immunoglobulin therapy in patients with Kawasaki disease
Lack of CD4+CD25+FOXP3+ regulatory T cells is associated with resistance to intravenous immunoglobulin therapy in patients with Kawasaki disease
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DOI：
10.1007/s00431-013-1937-3
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发表时间：
2013-06-01
影响因子：
3.6
通讯作者：
Kojima, Seiji
中科院分区：
文献类型：
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作者：
Hirabayashi, Yu;Takahashi, Yoshiyuki;Kojima, Seiji
本研究旨在探讨川崎（KD）患者外周血中CD 4（+）CD 25（+）FOXP 3（+）调节性T细胞（TCRs）的变化及其与静脉免疫球蛋白（IVIg）治疗反应的关系。参与者包括18名符合KD诊断标准的患者和20名健康受试者。应用流式细胞仪检测IVIg治疗前、治疗后7 d和30 d外周血单个核细胞中CD 4 + T细胞CD 25和FOXP 3的表达。治疗前，KD患者CD 4（+）CD 25（+）FOXP 3（+）T细胞占总CD 4（+）T细胞的百分比（4.19%;范围，0.16- 8.11%）显著低于健康受试者（7.32%; 4.18- 13.42%; P = 0.0001）。IVIG治疗后第7天CD 4（+）CD 25（+）FOXP 3（+）Tregs的百分比和绝对数量均较治疗前显着增加（8.02%（范围，0.51- 12.6%）vs. 4.19%）（范围，0.16- 8.11%），P = 0.0005; 93.25/μ L（范围，6.67-258.05）对41.85/μ L（范围，0.44-160.62），P < 0.0001）。IVIg耐药组治疗前CD 4（+）CD 25（+）FOXP 3（+）T细胞百分比和绝对数均显著低于IVIg敏感组（分别为0.18%（范围，0.16- 3.34%）对4.52%（范围，2.8- 8.11%），P = 0.0022; 0.68/μ L（范围，0.44-53.81）对51.66/μ L（范围，2.88-160.62），P = 0.0098）。在诊断时，5例IVIg耐药患者中有4例的CD 4（+）CD 25（+）FOXP 3（+）T细胞频率比健康受试者低3个标准差以上。这4例患者中有2例显示冠状动脉异常，其中1例发生冠状动脉瘤。结论：KD患儿治疗前CD 4（+）CD 25（+）FOXP 3（+）T细胞亚群缺失可能预示着对IVIg治疗的抵抗。
The aim of this study was to investigate changes in CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) throughout the clinical course of Kawasaki disease (KD) and correlations with response to intravenous immunoglobulin (IVIg) therapy. Participants comprised 18 patients who fulfilled the diagnostic criteria for KD and 20 healthy subjects. Expressions of CD25 and FOXP3 among all CD4(+) T cells in peripheral blood mononuclear cells were analyzed by flow cytometry before and 7 and 30 days after IVIg therapy. Before treatment, percentages of CD4(+)CD25(+)FOXP3(+) Tregs among total CD4(+) Tregs were significantly lower among KD patients (4.19 %; range, 0.16-8.11 %) than among healthy subjects (7.32 %; 4.18-13.42 %; P = 0.0001). Both percentages and absolute numbers of CD4(+)CD25(+)FOXP3(+) Tregs on day 7 after IVIg therapy were significantly increased compared with values before treatment (8.02 % (range, 0.51-12.6 %) vs. 4.19 % (range, 0.16-8.11 %), P = 0.0005; 93.25/ mu L (range, 6.67-258.05) vs. 41.85/ mu L (range, 0.44-160.62), P < 0.0001, respectively). Moreover, percentages and absolute numbers of CD4(+)CD25(+)FOXP3(+) Tregs before treatment were significantly lower in the IVIg-resistant group than in the IVIg-sensitive group (0.18 % (range, 0.16-3.34 %) vs. 4.52 % (range, 2.8-8.11 %), P = 0.0022; 0.68/mu L (range, 0.44-53.81) vs. 51.66/mu L (range, 2.88-160.62), P = 0.0098, respectively). The frequency of CD4(+)CD25(+)FOXP3(+) Tregs in four of the five IVIg-resistant patients at diagnosis was more than 3 standard deviations below that in healthy subjects. Two of these four patients displayed coronary abnormalities, and one of these two patients developed coronary aneurysm. Conclusion: Lack of CD4(+)CD25(+)FOXP3(+) Tregs before treatment may predict resistance to IVIg therapy in patients with KD.