Pathogenesis of Kawasaki disease : Gene expression in susceptible hosts determined by microarray

背景：尽管进行了广泛的研究，川崎病(KD)的病因仍不清楚。我们的假设表明，非常常见的感染性因素可能会在一些易感宿主中引起KD。我们利用Affymetrix基因芯片系统研究了KD患者和对照组之间基因表达的差异。方法：5例川崎病患者，年龄最小至年限，平均随访年限为10年，其中有冠状动脉病变组(A组，n=8)和无冠状动脉病变组(B组，n=8)，无川崎病病史(n=10)。我们分析了外周血中单个核细胞提供的RNA样本的基因表达谱。基因表达差异达1.5倍以上，差异有统计学意义。结果：KD患者的基因表达大部分相似。但3组间基因表达存在一定差异。T-…的人GREMLINE-IGD链基因和智囊虫基因有CALS的KD患者细胞白血病/淋巴瘤1的表达高于无CALS的KD患者。此外，KIAA0752蛋白的智人基因在伴有GALS的KD患者中的表达明显高于无CALS的KD患者。伴有GALS的川崎病患者较无川崎病病史的川崎病患者更易表达人类MHC-Ⅱ类抗原-DR7和人MHC-Ⅱ类分子I-ILA-DRV53的连接基因。人补体细胞溶解抑制因子(CLI)基因和精胺/精胺N1-乙酰转移酶(SS-A)基因在无KD病史的患者中的表达明显高于KD合并CALS患者。SS-A基因可能与血管疾病有关。已有报道认为SS-A基因在人脐静脉内皮细胞中的表达与切应力有关。结论：本研究提示一些遗传因素可能参与了川崎病的发病，尤其是与血管疾病相关的因素。目前的结果表明，进一步研究这些变化作为设计未来KD血管炎冠状动脉病变基因治疗的基线信息来源是有价值的。较少

Background : The etiology of Kawasaki disease (KD) remains unknown despite extensive investigations. Our hypothesis suggested that very common infectious agents might cause KD in some susceptible hosts. We investigated the difference of gene expression between patients with KD and control subjects by use the Affymetrix GeneChip system. Methods : Five patients with KD, ranged age from to years, mean follow up periods years, including Group A patients (n=8) who had coronary artery lesions GALs and Group B patients (n=8) who had no GALs, 2 patients who had no history of KD as controls (n=10), were studied. We analyzed a gene expression profile with RNA sample provided mononuclear cells in peripheral white blood cells. The difference of gene expression did more than 1.5 times with significance. Result : Most gene expression in KD patients was resembled. However some differences of gene expression were found among 3 groups. The gene of Human gremline IgD chain gene and H.sapiens mRNA for T … More cell lerkemia/lymphoma 1 were expressed on KD patients with CALs more than on patients with no CALs. In addition, the gene of Homo sapiens mRNA for KIAA0752 protein were expressed on KD patients with GALS more than on KD patients with no CALS. The connection gene of a Human MHC class II HLA-DR7 and Human MHC class II I-ILA-DRw53 were expressed on KD patients with GALS more than patients who had no history of KD. The gene of Human complement cytolysis inhibitor (CLI) mRNA and Spermidine/Spermine N1-Acetyltransferase (SS-A) were expression on patients without history of KD more than KD patients with CALs. SS-A gene may relate to vascular disease. Previous report suggested that gene expression of the SS-A related to the shear stress in human umbilical vein endothelial cells. Conclusion : This study suggested that some hereditary factors may participate in KD patients, especially to relate the factors of vascular disease. The present results demonstrate the merit of further investigation of the alterations as a source of baseline information for the design of future genetic therapy for coronary artery lesions due to KD vasculitis. Less