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基于 mtDNA 拷贝数的川崎病冠状动脉扩张的列线图预测。

A nomogram prediction of coronary artery dilation in Kawasaki diseases based on mtDNA copy number.

机构信息

Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education (MOE), Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

Department of Nursing, West China Second University Hospital, Sichuan University, Chengdu, China.

出版信息

Front Immunol. 2024 Aug 14;15:1448558. doi: 10.3389/fimmu.2024.1448558. eCollection 2024.

DOI:10.3389/fimmu.2024.1448558
PMID:39206185
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11349549/
Abstract

OBJECTIVE

The level of mitochondrial DNA copy number (mtDNA-CN) in peripheral blood cells had been identified to be involved in several immune and cardiovascular diseases. Thus, the aim of this study is to evaluate the levels of mtDNA-CN in Kawasaki disease (KD) and to construct a nomogram prediction for coronary artery lesions in children with KD.

METHODS

One hundred and forty-four children with KD diagnosed from March 2020 to March 2022 were involved in the study. The clinical features and laboratory test parameters of these children were assessed between the KD and normal groups. Univariable and multivariable analyses were performed sequentially to identify the essential risk factors. Subsequently, a nomogram prediction was constructed.

RESULTS

A total of 274 children were included in the analysis. Of these, 144 (52.6%) represented the KD group. Peripheral blood DNA mtDNA qPCR showed that the -log value of mtDNA-CN in the KD group (6.67 ± 0.34) was significantly higher than that in the healthy group (6.40 ± 0.18) (P<0.001). The area under the ROC curve for mtDNA-CN in distinguishing KD was 0.757. MtDNA-CN (OR = 13.203, P = 0.009, 95% CI 1.888-92.305), RBC (OR = 5.135, P = 0.014, 95% CI 1.394-18.919), and PA (OR = 0.959, P = 0.014, 95% CI 0.927-0.991) were identified as independent risk factors for coronary artery dilation in children with KD. Finally, the nomogram predictive was established based on the results of multivariable analysis, demonstrating the satisfied prediction and calibration values.

CONCLUSION

The results of this study revealed that mtDNA-CN could be used as a biomarker in predicting the development of KD. Furthermore, the higher the mtDNA-CN was significantly associated with coronary artery dilation in KD.

摘要

目的

外周血细胞中线粒体 DNA 拷贝数 (mtDNA-CN) 的水平已被确定与多种免疫和心血管疾病有关。因此,本研究旨在评估川崎病 (KD) 患者的 mtDNA-CN 水平,并构建用于预测 KD 患儿冠状动脉病变的列线图预测模型。

方法

纳入 2020 年 3 月至 2022 年 3 月期间确诊的 144 例 KD 患儿,评估 KD 组和正常组患儿的临床特征和实验室检查参数。依次进行单变量和多变量分析,以确定基本的危险因素。随后构建列线图预测模型。

结果

共纳入 274 例患儿,其中 144 例(52.6%)为 KD 组。外周血 DNA mtDNA qPCR 显示,KD 组 mtDNA-CN 的 -log 值(6.67±0.34)明显高于健康组(6.40±0.18)(P<0.001)。mtDNA-CN 鉴别 KD 的 ROC 曲线下面积为 0.757。mtDNA-CN(OR=13.203,P=0.009,95%CI 1.888-92.305)、红细胞计数(RBC,OR=5.135,P=0.014,95%CI 1.394-18.919)和血小板计数(PA,OR=0.959,P=0.014,95%CI 0.927-0.991)是 KD 患儿冠状动脉扩张的独立危险因素。最后,根据多变量分析结果建立了列线图预测模型,该模型具有较好的预测和校准值。

结论

本研究结果表明,mtDNA-CN 可作为预测 KD 发生的生物标志物。此外,mtDNA-CN 水平越高,与 KD 患儿冠状动脉扩张的相关性越强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ab/11349549/f84e18b2f298/fimmu-15-1448558-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ab/11349549/ddd0d98b5e3a/fimmu-15-1448558-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ab/11349549/8eafad00a3c4/fimmu-15-1448558-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ab/11349549/f84e18b2f298/fimmu-15-1448558-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ab/11349549/ddd0d98b5e3a/fimmu-15-1448558-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ab/11349549/8eafad00a3c4/fimmu-15-1448558-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ab/11349549/f84e18b2f298/fimmu-15-1448558-g003.jpg

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本文引用的文献

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Mitochondrial DNA-triggered innate immune response: mechanisms and diseases.线粒体 DNA 触发的固有免疫反应:机制与疾病。
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Roles of Oxidative Injury and Nitric Oxide System Derangements in Kawasaki Disease Pathogenesis: A Systematic Review.氧化损伤和一氧化氮系统紊乱在川崎病发病机制中的作用:系统评价。
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Mitochondrial SOS: how mtDNA may act as a stress signal in Alzheimer's disease.
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Single-cell individual full-length mtDNA sequencing by iMiGseq uncovers unexpected heteroplasmy shifts in mtDNA editing.通过 iMiGseq 对单细胞个体全长 mtDNA 进行测序揭示了 mtDNA 编辑中意想不到的异质性移位。
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