Song Sirui, Chen Liqin, Ning Qianqian, Zhu Danying, Qiu Feng, Li Guang, Zhang Hong, Xiao Tingting, Ding Guohui, Huang Min
Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Shanghai Center for Bioinformation Technology, Shanghai, People's Republic of China.
Int J Gen Med. 2022 Jan 22;15:837-848. doi: 10.2147/IJGM.S343225. eCollection 2022.
Kawasaki disease (KD) is an acute systemic vasculitis mainly found in the medium-sized arteries, especially the coronary arteries. Immune system is involved in the pathogenesis of acute KD in children, but the functional differences in the immune system between healthy children and KD patients remain unclear.
A total of 190 KD patients and 119 healthy controls were recruited for the next-generation sequencing of 512 targeted genes from 4 immune-related pathways. Subsequently, the peripheral blood mononuclear cells (PBMCs) were isolated. RNA sequencing of the LPS treated PBMCs from additional 20 KD patients and 20 healthy controls was used to examine the differentially expressed genes (DEGs). Then, an expression quantitative trait locus (eQTL) analysis combined with previously analyzed RNA data were used to examine the DEGs. Finally, the serum levels of 13 cytokines were detected before and after LPS treatment in 40 samples to confirm the findings from eQTL analysis.
A total of 319 significant eQTL were found, and both eQTL analysis and RNA sequencing showed some DEGs were involved in the connective tissue disorders and inflammatory diseases. DEGs that function to negatively regulate immunity were closely related to the pathogenesis of KD. In addition, the serum levels of IL-10 (an inflammatory and immunosuppressive factor) and SCD25 (an important immunosuppressant) reduced significantly in the KD patients.
Our study shows the expression of factors responsible for the negative control of innate immunity is altered, which plays an important role in the etiology of KD.
川崎病（KD）是一种主要累及中等大小动脉尤其是冠状动脉的急性全身性血管炎。免疫系统参与儿童急性KD的发病机制，但健康儿童与KD患者免疫系统的功能差异仍不清楚。
招募了190例KD患者和119例健康对照，对来自4条免疫相关途径的512个靶向基因进行二代测序。随后，分离外周血单个核细胞（PBMC）。对另外20例KD患者和20例健康对照经脂多糖（LPS）处理的PBMC进行RNA测序，以检测差异表达基因（DEG）。然后，结合先前分析的RNA数据进行表达数量性状位点（eQTL）分析，以研究DEG。最后，检测40份样本在LPS处理前后13种细胞因子的血清水平，以证实eQTL分析的结果。
共发现319个显著的eQTL，eQTL分析和RNA测序均显示一些DEG参与结缔组织疾病和炎症性疾病。具有负向调节免疫功能的DEG与KD的发病机制密切相关。此外，KD患者血清中白细胞介素-10（一种炎症和免疫抑制因子）和可溶性白细胞介素-2受体α链（一种重要的免疫抑制剂）水平显著降低。
我们的研究表明，负责先天免疫负调控的因子表达发生改变，这在KD的病因学中起重要作用。
