Huang Ying-Hsien, Chen Kuang-Den, Kuo Kuang-Che, Guo Mindy Ming-Huey, Chang Ling-Sai, Yang Ya-Ling, Kuo Ho-Chang
Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
Diagnostics (Basel). 2022 Jan 19;12(2):240. doi: 10.3390/diagnostics12020240.
Kawasaki disease (KD) is a febrile childhood vasculitis that involves the coronary arteries. Most previous studies have focused on the genes activated in the acute phase of KD. However, in this study, we focused on suppressed genes in the acute stage of KD and identified novel targets with clinical significance and potential prognostic value for KD patients. We enrolled 18 patients with KD, 18 healthy controls (HC), and 18 febrile controls (FC) for human transcriptome array analysis. Another 19 healthy controls, 20 febrile controls, and 31 patients with KD were recruited for RT-PCR validation of target mRNA expressions. The results of Human Transcriptome Array (HTA) 2.0 showed 461 genes that were significantly higher in KD and then normalized after IVIG, as well as 99 suppressed genes in KD. Furthermore, we identified the four genes in KD with the most downregulation, including BCL11B, DUSP2, DDX24, and CDR2, as well as the upregulation of their expression following IVIG administration. The mRNA expression of CDR2 by qRT-PCR was the most compatible with the pattern of the HTA2.0 results. Furthermore, we found higher DDX24 mRNA expression in KD patients with CAL when compared to those without CAL 3 weeks after IVIG administration. In summary, activated gene expression represented a majority in the immune response of KD. In this study, we identified CDR2 as a novel suppressed gene for Kawasaki disease via human transcriptome array analysis and DDX24 associated with CAL formation, which may contribute to further understanding of CAL pathogenesis in KD.
川崎病（KD）是一种累及冠状动脉的儿童发热性血管炎。此前大多数研究都集中在KD急性期激活的基因上。然而，在本研究中，我们聚焦于KD急性期受抑制的基因，并确定了对KD患者具有临床意义和潜在预后价值的新靶点。我们纳入了18例KD患者、18例健康对照（HC）和18例发热对照（FC）进行人类转录组阵列分析。另外招募了19例健康对照、20例发热对照和31例KD患者进行靶mRNA表达的RT-PCR验证。人类转录组阵列（HTA）2.0的结果显示，KD中有461个基因显著上调，静脉注射免疫球蛋白（IVIG）后恢复正常，还有99个基因在KD中受抑制。此外，我们确定了KD中下调最明显的四个基因，包括BCL11B、DUSP2、DDX24和CDR2，以及IVIG给药后它们表达的上调。通过qRT-PCR检测，CDR2的mRNA表达与HTA2.0结果模式最为相符。此外，我们发现IVIG给药3周后，有冠状动脉病变（CAL）的KD患者中DDX24的mRNA表达高于无CAL的患者。总之，激活的基因表达在KD的免疫反应中占多数。在本研究中，我们通过人类转录组阵列分析确定CDR2是川崎病一个新的受抑制基因，以及DDX24与CAL形成有关，这可能有助于进一步了解KD中CAL的发病机制。
