Kawasaki Disease Center, Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 33302, Taiwan.
Institute for Translational Research in Biomedicine, Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 33302, Taiwan.
Int J Mol Sci. 2022 Sep 3;23(17):10093. doi: 10.3390/ijms231710093.
Eosinophils may rise to a higher level in the acute phase of Kawasaki disease (KD) both before and after intravenous immunoglobulin (IVIG) therapy. A substantial body of research was carried out on the association between KD and allergic diseases. Eosinophils play an important role in type 2 inflammation. Recent studies have shown that there are two distinct subtypes of eosinophils. In addition to their role in inflammation, lung-resident eosinophils (rEOS) also regulate homeostasis. Inflammatory eosinophils (iEOS) reflect type 2 inflammation in tissues. iEOS were considered the primary eosinophils in non-severe allergic asthma, while rEOS were thought to be the primary eosinophils in severe non-allergic eosinophilic asthma. This case-control study aimed to investigate the marker expression of eosinophilic subtypes in KD patients.
The marker expressions of eosinophilic subtypes in the leukocytes of patients with KD were evaluated by the recently established KDmarkers online tool, a web server including gene expression data. Finally, the results were validated with a quantitative reverse transcriptase polymerase chain reaction (RT-PCR). We analyzed the mRNA expression levels of and in leukocytes from KD patients and febrile children.
Included in our screening tools were transcriptome arrays, which provided clues showing the importance of rEOS, whose role was identified by three genes (lower , higher and than controls). In contrast, the iEOS representative gene was not elevated in KD. It was found that the gene , a marker of inflammatory eosinophilic leukocytes, was more highly expressed in the leukocytes of KD patients ( = 43) than febrile controls ( = 32), especially those without coronary artery lesions (CAL) ( = 26). Before treatment, expression was higher in leukocytes of CAL patients (CAL, 1.33 ± 0.18, = 39; non-CAL, 0.87 ± 0.12, = 55; = 0.012). was significantly higher after half a year compared to febrile controls.
To our knowledge, this is the first study to demonstrate that KD patients have increased than febrile controls after 6 months of treatment. We present evidence here that dynamically different eosinophilic involvement exists between KD patients with and without CAL. The role of eosinophilic subtypes in KD patients warrants further investigation.
嗜酸性粒细胞在川崎病(KD)的急性期,无论是在静脉注射免疫球蛋白(IVIG)治疗前还是治疗后,都可能升高到更高水平。大量研究表明,KD 与过敏性疾病之间存在关联。嗜酸性粒细胞在 2 型炎症中发挥重要作用。最近的研究表明,嗜酸性粒细胞存在两种不同的亚型。除了在炎症中的作用外,肺驻留嗜酸性粒细胞(rEOS)还调节稳态。组织中的炎症性嗜酸性粒细胞(iEOS)反映了 2 型炎症。iEOS 被认为是非严重过敏哮喘的主要嗜酸性粒细胞,而 rEOS 被认为是严重非过敏嗜酸性哮喘的主要嗜酸性粒细胞。本病例对照研究旨在探讨 KD 患者嗜酸性粒细胞亚型的标记物表达。
通过最近建立的 KDmarkers 在线工具评估 KD 患者白细胞中嗜酸性粒细胞亚型的标记物表达,该在线工具是一个包含基因表达数据的网络服务器。最后,通过定量逆转录聚合酶链反应(RT-PCR)进行验证。我们分析了 KD 患者和发热儿童白细胞中 和 的 mRNA 表达水平。
纳入我们的筛选工具的是转录组芯片,这些芯片提供了提示 rEOS 重要性的线索,其作用通过三个基因(较低的 、较高的 和 )来确定。相比之下,iEOS 代表基因 在 KD 中没有升高。研究发现,炎症性嗜酸性白细胞的标记基因 在 KD 患者( = 43)的白细胞中的表达高于发热对照组( = 32),尤其是无冠状动脉病变(CAL)的患者( = 26)。在治疗前,CAL 患者白细胞中的 表达(CAL,1.33 ± 0.18, = 39;非-CAL,0.87 ± 0.12, = 55; = 0.012)高于非 CAL 患者。治疗半年后, 表达明显高于发热对照组。
据我们所知,这是第一项表明 KD 患者在治疗 6 个月后 高于发热对照组的研究。我们在这里提供的证据表明,CAL 和非 CAL 的 KD 患者之间存在动态不同的嗜酸性粒细胞参与。嗜酸性粒细胞亚型在 KD 患者中的作用值得进一步研究。