Analysis of biomarker serum levels in IVIG and infliximab refractory Kawasaki disease patients
Analysis of biomarker serum levels in IVIG and infliximab refractory Kawasaki disease patients
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DOI：
10.1007/s10067-017-3952-7
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发表时间：
2018-07-01
影响因子：
3.4
通讯作者：
Agematsu, Kazunaga
中科院分区：
文献类型：
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作者：
Hachiya, Akira;Kobayashi, Norimoto;Agematsu, Kazunaga
英夫利昔单抗（IFX）是治疗难治性川崎的有效药物。然而，IFX疗效的确切机制和生物标志物尚不清楚。我们试图通过测定血清细胞因子水平来评估IFX治疗的效果和反应。29名对两个疗程的大剂量静脉注射免疫球蛋白抵抗的KD儿童入选并接受IFX治疗。在IFX施用之前和之后分析血浆样品的细胞因子。IFX治疗前血清白细胞介素-6、粒细胞集落刺激因子（G-CSF）、干扰素-γ诱导的单核因子、干扰素-γ诱导蛋白10（IP-10）、单核细胞趋化蛋白1和可溶性肿瘤坏死因子-α受体（sTNFR）1和2水平显著升高，但给药后迅速下降。IFX无应答者治疗前G-CSF和sTNFR 1水平显著高于应答者，应答者定义为退热患者（< 37.5 A ℃）。IFX给药后，应答者升高的细胞因子降至正常范围，但在无应答组，G-CSF和sTNFR 1仍升高，未降至正常水平。IFX治疗显著降低了难治性KD患者血清细胞因子、趋化因子和sTNFR的水平。G-CSF和sTNFR 1可能是预测IFX反应不良的指标。
Infliximab (IFX) is effective for treatment of refractory Kawasaki disease (KD). However, the precise mechanisms and biomarkers for IFX efficacy are unknown. We tried to evaluate the effect and response to IFX therapy by measuring serum cytokine levels. Twenty-nine children with KD who had been resistant to two courses of high-dose intravenous immunoglobulin were enrolled and treated with IFX. Plasma samples were analyzed for cytokines before and after IFX administration. Serum levels of interleukin-6, granulocyte colony-stimulating factor (G-CSF), interferon-gamma-induced monokine, interferon-gamma inducible protein 10 (IP-10), monocyte chemotactic protein 1, and soluble tumor necrosis factor-alpha receptor (sTNFR) 1 and 2 were significantly elevated before IFX treatment, but promptly decreased after the administration. The pre-treatment G-CSF and sTNFR1 levels in non-responders to IFX were significantly higher than in responders, who were defined as patients who defervesce (< 37.5 A degrees C). After IFX administration, elevated cytokines declined to normal ranges in responders, but in non-responsive group, G-CSF and sTNFR1 remained elevated without failing to normal levels. IFX treatment significantly reduced the levels of serum cytokines, chemokines, and sTNFRs in refractory KD. G-CSF and sTNFR1 may be indicators predictive of poor response to IFX.