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Pathogenesis and therapeutic strategy of Kawasaki disease : Gene expression determined by microarray study

川崎病的发病机制和治疗策略：通过微阵列研究确定基因表达

基本信息

批准号：
18591166
负责人：
ISHII Masahiro
金额：
$ 2.49万
依托单位：
Kitasato University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591166/
关键词：
Kawasaki Disease coronary aneurysm immunoglobulin therapy RNA microarray gene expression steroid pulse therapy Kurume score 分子遺伝学的基盤ステロイドパルスサイトカイン TNF-α 抗サイトカイン療法

项目摘要

Background: Although high-dose intravenous immunoglobulin (IVIG) treatment in the acute stage of Kawasaki disease (KD) has shown to be effective, 10% to 20% of severe KD patients are resistant to initial IVIG treatment. We could predict these severe KD patients using Kurume score for evaluation score of severity of KD (J. Pediater, 2006). We analyzed RNA expression of whole blood s of KD patients using microarray. We investigated relationship to gene expression and severity of KD and to assess the effect of therapeutic strategy by changes of gene expression before and after initial treatment Method: The gene expression of 11 KD patients at Kitasato University, from April 2007 to December 2007 were studied using microarray system. Those patients divided into 2 groups using Kurume scare (Cut off points; 3). 6 KD patients were severe cases (〓3), 5 KD patients were mild cases(〓2). In severe KD patients groups, we randomly divided into 2 groups by different initial treatment strategy 3 pati … More ents were treated with WIG therapy for initial treatment, another 3 patients were treated with MG therapy plus steroid pulse therapy(Methyl-prednisolone: 30mg/kg/day, 1day) for initial treatment. Result: Those were significant differences in gene expression between mild KD patients and severe KD patients. The 1226 genes of 66577 genes of severe cases were expression higher than those of mild cases. The Toll-like receptor signaling pathway associated genes, cytokine-cytokine receptor interaction associated genes were especially high expression in severe cases. The significant differences were found in the decreased gene expression between 3 patients with IVIG therapy for initial treatment and 3 patients with IVIG plus steroid pulse therapy for initial treatment. The 254 genes expression were decreased by WIG treatment, and 5249 gene expression were decreased by MG plus steroid pulse therapy. The WIG plus steroid pulse therapy widely suppressed gene expression related to inflammation. Conclusion: The present results demonstrated the merit of further investigation of the alteration as a source of base line information for the design of future strategy of KD vasculitis. Less

背景：虽然高剂量静脉注射免疫球蛋白（IVIG）治疗川崎病（KD）急性期已被证明是有效的，但10%至20%的严重川崎病患者对初始IVIG治疗有耐药性。我们可以使用Kurume评分作为KD严重程度的评估评分来预测这些严重KD患者（J. Pediater, 2006）。我们采用芯片技术分析KD患者全血RNA表达。我们研究了基因表达与KD严重程度的关系，并通过初始治疗前后基因表达的变化来评估治疗策略的效果。方法：使用微阵列系统研究了2007年4月至2007年12月北中大学11例KD患者的基因表达。采用切点法将患者分为两组，重症患者6例（= 3），轻症患者5例（= 2）。在重症KD患者组中，我们根据不同的初始治疗策略随机分为2组，其中3例患者采用WIG治疗初始治疗，另外3例患者采用MG治疗加类固醇脉冲治疗（甲基强的松龙：30mg/kg/day， 1day）初始治疗。结果：轻度KD患者与重度KD患者基因表达差异有统计学意义。重症患者66577个基因中1226个基因表达量高于轻症患者。在重症病例中，toll样受体信号通路相关基因、细胞因子-细胞因子受体相互作用相关基因的表达尤其高。3例初始使用IVIG治疗的患者与初始使用IVIG加类固醇脉冲治疗的患者基因表达下降有显著差异。WIG组有254个基因表达降低，MG +类固醇脉冲组有5249个基因表达降低。WIG加类固醇脉冲治疗广泛抑制与炎症相关的基因表达。结论：目前的结果证明了进一步研究这种改变作为未来KD血管炎策略设计的基线信息来源的优点。少