IFI44L 的 DNA 甲基化作为儿童发病系统性红斑狼疮的潜在血液生物标志物。
DNA methylation of IFI44L as a potential blood biomarker for childhood-onset systemic lupus erythematosus.
机构信息
Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
出版信息
Pediatr Res. 2024 Jul;96(2):494-501. doi: 10.1038/s41390-024-03135-1. Epub 2024 Mar 21.
BACKGROUND
IFN-induced protein 44-like (IFI44L) promoter methylation has been demonstrated to serve as an effective blood diagnostic biomarker for adult-onset SLE. However, its utility as a diagnostic marker for childhood-onset SLE (cSLE) remains to be verified.
METHODS
Initially, we conducted a differential analysis of gene methylation and mRNA expression patterns in cSLE whole blood samples obtained from the public GEO database to determine IFI44L gene expression and assess the methylation status at its CpG sites. Subsequently, we collected clinical whole blood samples from 49 cSLE patients and 12 healthy children, employing an HRM-qPCR-based IFI44L methylation detection technique to evaluate its diagnostic efficacy in pediatric clinical practice.
RESULTS
A total of 26 hypomethylated, highly expressed genes in cSLE were identified by intersecting differentially expressed genes (DEGs) and differentially methylation genes (DMGs). GO enrichment analysis for these 26 genes indicated a robust association with type I IFN. Among the overlapping genes, IFI44L exhibited the most pronounced differential expression and methylation. In subsequent clinical validation experiments, IFI44L methylation was confirmed as an effective blood-based diagnostic biomarker for cSLE, achieving an AUC of 0.867, a sensitivity of 0.753, and a specificity of 1.000.
CONCLUSIONS
IFI44L methylation is a promising blood biomarker for cSLE.
IMPACT
IFI44L promoter methylation was reported to serve as a highly sensitive and specific diagnostic marker for adult-onset SLE. However, the diagnostic efficacy of IFI44L in childhood-onset SLE (cSLE) still remains to be confirmed. In this study, we utilized bioinformatics analysis and conducted clinical experiments to demonstrate that IFI44L methylation can also serve as a promising blood biomarker for cSLE. The findings of this study can facilitate the diagnosis of cSLE and broaden our understanding of its molecular mechanisms, with a particular focus on those related to type I interferons.
背景
干扰素诱导蛋白 44 样（IFI44L）启动子甲基化已被证明是成人发病的系统性红斑狼疮（SLE）有效的血液诊断生物标志物。然而，其作为儿童发病的系统性红斑狼疮（cSLE）的诊断标志物的效用仍有待验证。
方法
首先，我们对公共 GEO 数据库中获得的 cSLE 全血样本的基因甲基化和 mRNA 表达模式进行了差异分析，以确定 IFI44L 基因的表达，并评估其 CpG 位点的甲基化状态。随后，我们收集了 49 例 cSLE 患者和 12 例健康儿童的临床全血样本，采用 HRM-qPCR 检测技术对 IFI44L 甲基化进行检测，以评估其在儿科临床实践中的诊断效能。
结果
通过交集差异表达基因（DEGs）和差异甲基化基因（DMGs），鉴定出 26 个在 cSLE 中低甲基化、高表达的基因。这些 26 个基因的 GO 富集分析表明与 I 型干扰素具有很强的相关性。在重叠基因中，IFI44L 表现出最显著的差异表达和甲基化。在随后的临床验证实验中，IFI44L 甲基化被证实是 cSLE 的一种有效的血液诊断生物标志物，AUC 为 0.867，灵敏度为 0.753，特异性为 1.000。
结论
IFI44L 甲基化是一种有前途的 cSLE 血液生物标志物。
影响
IFI44L 启动子甲基化被报道是成人发病的系统性红斑狼疮（SLE）的高度敏感和特异性诊断标志物。然而，IFI44L 在儿童发病的系统性红斑狼疮（cSLE）中的诊断效能仍有待证实。在这项研究中，我们利用生物信息学分析并进行了临床实验，证明 IFI44L 甲基化也可以作为 cSLE 的一种有前途的血液生物标志物。本研究的发现有助于 cSLE 的诊断，并拓宽我们对其分子机制的认识，特别是与 I 型干扰素相关的机制。
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