Abstract
Intravenous immunoglobulin (IVIG) resistance was a major cause of coronary artery lesions in children with Kawasaki disease (KD). However, the cause of IVIG resistance in KD remains unknown. miR-221-3p has been confirmed involved in cardiovascular diseases and rheumatoid arthritis. The purpose of this study was to investigate the association between miR-221-3p and IVIG resistance in children with KD. Fifty-five KD patients and 29 healthy controls (HCs) were enrolled in this study. KD patients were divided into group of sensitive to IVIG (IVIG-response, n = 42) and group of resistant to IVIG (IVIG-resistance, n = 13), group of 10 KD patients with coronary artery lesions (CALs, KD-CALs) and group of 10 sex- and age-matched KD patients without CALs (KD-NCALs). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of miR-221-3p. Compared with the HCs group, miR-221-3p were significantly increased in the KD group (p < 0.05), and the IVIG-resistance group had higher levels of miR-221-3p than those in the IVIG-response group (p < 0.05). CRP (C-reactive protein), PCT (procalcitonin), NLR (neutrophil-lymphocyte ratio) were positively correlated with miR-221-3p in KD patients. In addition, the group of IVIG resistance had a higher level of Kobayashi Score (p < 0.001). The receiver operating characteristic curve showed that miR-221-3p had a better value for diagnosis IVIG resistance in children with KD than Kobayashi Score with the AUC of 0.811 (95% CI, 0.672-0.951), 0.793 (95% CI, 0.618-0.968), respectively. Additionally, miR-221-3p was elevated (p < 0.05) and showed an AUC value of 0.83 (95% CI, 0.648-1.000, p < 0.05) for the prediction of the complication of coronary artery abnormalities in the group of KD with CALs. miR-221-3p might be involved in the pathogenesis of KD and IVIG resistance and miR-221-3p can be used as a new potential biomarker to predict IVIG resistance in children with KD.
Highlights
Kawasaki disease (KD) is an acute self-limiting febrile vasculitis that mainly affects children under five years old [1]
The receiver operating characteristic (ROC) curve showed that miR-221-3p had a better value for diagnosis Intravenous immunoglobulin (IVIG) resistance in children with KD than Kobayashi Score and the combination of both with the area under the ROC curve (AUC) of 0.811, 0.793 and 0.797, respectively
Conclusions miR-221-3p might be involved in the pathogenesis of KD and IVIG resistance and miR-221-3p can be used as a new potential biomarker to predict of IVIG resistance in children with KD
Summary
Kawasaki disease (KD) is an acute self-limiting febrile vasculitis that mainly affects children under five years old [1]. Since its first discovery in 1960s, KD has been identified worldwide and become the leading cause of acquired heart disease in children in developed countries [2]. Further research regarding the pathogenesis of IVIG resistance in children with KD is necessary. Pandis et al found that the expression levels of miR-221 were significantly higher in synovial fibroblast (SF) in patients with rheumatoid arthritis (RA) [12]. Yang et al demonstrated that downregulation of miR-221 can significantly inhibit the levels of TNF-α, IL-6, IL-1β and CXCL16 in fibroblast-like synoviocytes (FLS) cells in patients with RA [13]. Studies have found that miR-221 expression increases significantly in acute KD patients [14]. The purpose of this study is to investigate the role of miR-2213p on IVIG resistance in children with KD
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