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.

中文翻译：

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IFI44L 的 DNA 甲基化作为儿童期发病的系统性红斑狼疮的潜在血液生物标志物

背景

IFN 诱导的蛋白 44 样 ( IFI44L ) 启动子甲基化已被证明可作为成人发病 SLE 的有效血液诊断生物标志物。然而，其作为儿童期 SLE (cSLE) 诊断标志物的实用性仍有待验证。

方法

最初，我们对从公共 GEO 数据库获得的 cSLE 全血样本中的基因甲基化和 mRNA 表达模式进行了差异分析，以确定IFI44L基因表达并评估其 CpG 位点的甲基化状态。随后，我们收集了 49 名 cSLE 患者和 12 名健康儿童的临床全血样本，采用基于 HRM-qPCR 的IFI44L甲基化检测技术来评估其在儿科临床实践中的诊断效果。

结果

通过交叉差异表达基因 (DEG) 和差异甲基化基因 (DMG) 鉴定出 cSLE 中总共 26 个低甲基化、高表达的基因。这 26 个基因的 GO 富集分析表明与 I 型 IFN 存在很强的相关性。在重叠基因中，IFI44L表现出最明显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的有效血液诊断生物标志物，其AUC为0.867，敏感性为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

• 据报道， IFI44L启动子甲基化可作为成人发病的 SLE 的高度敏感和特异性诊断标志物。然而， IFI44L对儿童期 SLE (cSLE)的诊断功效仍有待证实。在本研究中，我们利用生物信息学分析并进行临床实验来证明IFI44L甲基化也可以作为 cSLE 的有前途的血液生物标志物。这项研究的结果可以促进 cSLE 的诊断，并拓宽我们对其分子机制的理解，特别关注与 I 型干扰素相关的分子机制。