Identifying Circulating MicroRNA in Kawasaki Disease by Next-Generation Sequencing Approach.

Ken-Pen Weng,Luo-Ping Ger,Kuang-Jen Chien,Shih-Hui Huang,Ching-Feng Cheng,Kuo-Wang Tsai

doi:10.3390/cimb43020037

Abstract

Kawasaki disease (KD) typically occurs in children aged under 5 years and can cause coronary artery lesions (CALs). Early diagnosis and treatment with intravenous immunoglobulin can reduce the occurrence of CALs; therefore, identifying a good biomarker for diagnosing KD is essential. Here, using next-generation sequencing in patients with recurrent KD, those with viral infection, and healthy controls, we identified dysregulated circulating microRNAs as diagnostic biomarkers for KD. Pathway enrichment analysis illustrated the putative role of these miRNAs in KD progression. Their expression levels were validated using real-time polymerase chain reaction (qPCR). Fifteen dysregulated circulating miRNAs (fold changes >2 and <0.5) were differentially expressed in the recurrent KD group compared with the viral infection and control groups. These miRNAs were significantly involved in the transforming growth factor-β, epithelial–mesenchymal transition, and cell apoptosis signaling pathways. Notably, their expression levels were frequently restored after intravenous immunoglobulin treatment. Among the candidates, miR-24-3p expression level was significantly higher in patients with recurrent KD compared with healthy controls or viral infection controls (p < 0.001). Receiver operating characteristic analysis revealed that high miR-24-3p expression levels may be a potential biomarker for KD diagnosis. In conclusion, we identified miR-24-3p significantly higher in KD patients, which may be a potential diagnostic biomarker for KD.

Highlights

Kawasaki disease (KD) is a rare systemic inflammatory disease that typically occurs in children under 5 years of age [1]
We identified seven upregulated and eight downregulated circulating miRNAs in patients with KD compared with the levels in patients with viral infection, and the altered expression levels of these miRNAs were reversed after intravenous immunoglobulin (IVIG) treatment
transforming growth factor (TGF)-β may contribute to aneurysm formation by inducing myofibroblast generation through the epithelial–mesenchymal transition (EMT) in the arterial wall of patients with KD [45]

Summary

Introduction

Kawasaki disease (KD) is a rare systemic inflammatory disease that typically occurs in children under 5 years of age [1]. KD diagnosis depends on clinical signs and inflammatory markers, including the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and total leucocyte count. Except for these features and laboratory characteristics, cytokines are used as auxiliary biomarkers for KD diagnosis, including interleukin (IL)-1, tumor necrosis factor-α, interferon-γ, IL-4, IL-6, IL-8, and IL-10 [13,14,15,16,17,18]. These cytokines have been shown to be significantly increased during acute KD. The availability of a favorable biomarker for early diagnosis of KD and treatment initiation with a single high dose of IVIG will help reduce the incidence of CALs [9,19]

Methods

Results

Conclusion