Kuo Kuang-Che, Yang Ya-Ling, Lo Mao-Hung, Cai Xin-Yuan, Kuo Ho-Chang, Huang Ying-Hsien
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Front Pediatr. 2020 Dec 3;8:592122. doi: 10.3389/fped.2020.592122. eCollection 2020.
Kawasaki disease (KD) is the most common form of febrile coronary vasculitis disease to occur in children. Early diagnosis and proper therapy can prevent the complication of coronary artery lesions (CAL). The main pathogenesis of KD is an inflammatory process related to the host's genetic characteristics. In innate human immunity, the interaction of leukocytes and glycoprotein plays an important role against microbes. The purpose of our study was to understand the role of leukocytes' glycoprotein genes during the acute phase of KD. We enrolled a total of 97 subjects from a medical center. Of those, 24 subjects were healthy controls, and 24 subjects were fever controls; the other 49 subjects were KD patients who had had blood samples taken both before and after IVIG treatment. We collected the total RNA from leukocytes and performed a quantitative polymerase chain reaction for the HP, GRP84, and CLEC4D genes in real time. Compared with both the healthy and fever controls, the upregulation of HP, GRP84, and CLEC4D genes was significant in peripheral leukocytes during acute-phase KD. The transcriptional level of these respective genes not only demonstrated a positive correlation with each other, but were also effective predictors for KD (all auROC >0.87) according to the ROC curve analysis. The hyper-expression of these three genes was significantly associated with IVIG resistance, but not CAL formation. Our study demonstrates that the expression of HP, GRP84, and CLEC4D genes of leukocytes play an important role in the pathogenesis and primary IVIG response during the acute inflammatory process of KD.
川崎病(KD)是儿童发热性冠状动脉血管炎疾病最常见的形式。早期诊断和恰当治疗可预防冠状动脉病变(CAL)并发症。KD的主要发病机制是与宿主遗传特征相关的炎症过程。在人类先天免疫中,白细胞与糖蛋白的相互作用在抵御微生物方面发挥重要作用。我们研究的目的是了解白细胞糖蛋白基因在KD急性期的作用。我们从一家医疗中心共招募了97名受试者。其中,24名受试者为健康对照,24名受试者为发热对照;另外49名受试者为KD患者,他们在静脉注射免疫球蛋白(IVIG)治疗前后均采集了血样。我们从白细胞中提取总RNA,并对HP、GRP84和CLEC4D基因进行实时定量聚合酶链反应。与健康对照和发热对照相比,急性期KD患者外周血白细胞中HP基因、GRP84基因和CLEC4D基因的表达上调显著。这些基因各自的转录水平不仅相互呈正相关,而且根据ROC曲线分析,它们还是KD的有效预测指标(所有曲线下面积均>0.87)。这三个基因的高表达与IVIG抵抗显著相关,但与CAL形成无关。我们的研究表明,白细胞的HP基因、GRP84基因和CLEC4D基因的表达在KD急性炎症过程的发病机制和对IVIG的初始反应中起重要作用。