Jone Pei-Ni, Korst Armin, Karimpour-Fard Anis, Thomas Thomas, Dominguez Samuel R, Heizer Heather, Anderson Marsha S, Glode Mary P, Sucharov Carmen C, Miyamoto Shelley D
Pediatric Cardiology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA.
Department of Medicine, University of Colorado Anschutz, Aurora, CO, USA.
J Mol Cell Cardiol. 2020 Sep;146:12-18. doi: 10.1016/j.yjmcc.2020.06.011. Epub 2020 Jul 4.
Kawasaki Disease (KD) is an acute vasculitis of unknown etiology in children that can lead to coronary artery lesions (CAL) in 25% of untreated patients. There is currently no diagnostic test for KD, and the clinical presentation is often difficult to differentiate from other febrile childhood illnesses. Circulating microRNAs (miRNAs) are small noncoding RNA molecules that control gene expression by inducing transcript degradation or by blocking translation. We hypothesize that the expression of circulating miRNAs will differentiate KD from non-KD febrile illnesses in children.
Circulating miRNA profiles from 84 KD patients and 29 non-KD febrile controls (7 viral and 22 bacterial infections) were evaluated. 3 ul of serum from each subject was submitted to 3 freeze/heat cycles to ensure miRNA release from microvesicles or interaction with serum proteins. miRNAs were reverse transcribed using a pool of primers specific for each miRNA. Real-time PCR reactions were performed in a 384 well plate containing sequence-specific primers and TaqMan probes in the ABI7900. '.
KD patients (3.6 ± 2.2 yrs., 58% male) were found to have a unique circulating miRNA profile, including upregulation of miRNA-210-3p, -184, and -19a-3p (p < .0001), compared to non-KD febrile controls (8.5 ± 6.1 yrs., 72% male).
Circulating miRNAs can differentiate KD from infectious febrile childhood diseases, supporting their potential as a diagnostic biomarker for KD.
川崎病(KD)是一种病因不明的儿童急性血管炎,在25%未经治疗的患者中可导致冠状动脉病变(CAL)。目前尚无针对KD的诊断测试,其临床表现往往难以与其他儿童发热性疾病相区分。循环微RNA(miRNA)是小的非编码RNA分子,通过诱导转录本降解或阻断翻译来控制基因表达。我们假设循环miRNA的表达将使KD与儿童非KD发热性疾病相区分。
评估了84例KD患者和29例非KD发热对照(7例病毒感染和22例细菌感染)的循环miRNA谱。将每个受试者的3微升血清进行3次冻融循环,以确保miRNA从微泡中释放或与血清蛋白相互作用。使用针对每种miRNA的一组引物对miRNA进行逆转录。在含有序列特异性引物和TaqMan探针的384孔板中于ABI7900上进行实时PCR反应。
发现KD患者(3.6±2.2岁,58%为男性)与非KD发热对照(8.5±6.1岁,72%为男性)相比,具有独特的循环miRNA谱,包括miRNA-210-3p、-184和-19a-3p上调(p<.0001)。
循环miRNA可将KD与儿童感染性发热疾病区分开来,支持其作为KD诊断生物标志物的潜力。