调节性T细胞Foxp3基因在川崎病发生发展中的作用及其诊断价值研究-现代医学

调节性T细胞Foxp3基因在川崎病发生发展中的作用及其诊断价值研究

单位：1. 南京市溧水区中医院检验科, 南京 211200;
2. 南京医科大学附属儿童医院检验科, 南京 210008

关键词：川崎病调节性T细胞叉状头转录因子3 mTORC1-HIF-1α-糖酵解通路

分类号：R725.4

出版年·卷·期（页码）：2026·54·第五期（741-747）

摘要：

目的：检测川崎病(KD)患儿外周血调节性T细胞(Tregs)叉状头转录因子3(Foxp3)基因的表达水平，评价其作为KD患儿早期诊断标志物的价值并初步探讨其参与KD发生的机制。方法：流式细胞术检测31例急性期KD、9例恢复期KD患儿和13例健康对照儿童外周血中CD4⁺Foxp3⁺ Tregs及CD8⁺Foxp3⁺ Tregs的表达比例。实时荧光定量PCR 检测KD患儿外周血单个核细胞中Foxp3，mTORC1-HIF-1α-糖酵解通路相关基因mRNA表达水平，Spearman相关性分析Foxp3表达与该通路各基因间的相关性。采用受试者工作特征曲线(ROC)评价Tregs Foxp3基因对早期KD的预测能力及最佳截断值。结果：与健康对照组相比，急性期KD患儿CD4⁺Foxp3⁺ Tregs及CD8⁺Foxp3⁺Tregs的比例明显降低(P<0.05)；恢复期KD患儿CD4⁺Foxp3⁺ Tregs及CD8⁺Foxp3⁺Tregs的比例较急性期KD患儿显著升高(P<0.005)，较健康对照组无显著差异。基因集富集分析(GSEA)分析结果显示KD中Foxp3表达水平变化时，mTOR信号通路变化显著。Foxp3表达水平与mTOR信号通路活性呈正相关，临床标本验证结果与GSEA分析结果一致。Tregs Foxp3基因用于诊断KD的ROC曲线下面积(AUC)为0.866(95%CI 0.794~0.938)，最佳截断值为0.409，敏感性为94.1%，特异性为72.5%。结论：Tregs Foxp3基因在KD的发生中发挥重要作用，KD患儿Foxp3水平降低可能与mTORC1-HIF-1α-糖酵解通路相关，Tregs Foxp3基因对评估KD发生具有一定的预测价值，可作为KD早期诊断的辅助手段。

Objective: This study aimed to detect the expression of forkhead box P3(Foxp3) in peripheral blood regulatory T cells(Tregs) of children with Kawasaki disease(KD), evaluate its value as an early diagnostic biomarker, and preliminarily explore its underlying mechanisms in KD pathogenesis. Methods:Flow cytometry was employed to assess the ratios of CD4⁺Foxp3⁺Tregs and CD8⁺Foxp3⁺Tregs in the peripheral blood of 31 acute KD patients, 9 convalescent KD patients, and 13 healthy control(HC). Quantitative PCR was utilized to determine the expression of Foxp3 and mTORC1-HIF-1α-glycolysis pathway-related genes in the peripheral blood mononuclear cells of KD patients. Spearman analysis was performed to evaluate the correlation between Foxp3 expression and glycolysis pathway-related genes. Receiver operating characteristic(ROC) curve was constructed to evaluate the diagnostic value and identify the optimal cutoff value. Results: Both CD4⁺Foxp3⁺Tregs and CD8⁺Foxp3⁺ Tregsproportions were significantly reduced in children with acuteKD compared to HC. During convalescence, these proportions significantly recovered. Gene set enrichment analysis(GSEA) revealed that Foxp3 expression in KD were significantly associated with mTOR signaling pathway. Clinical data further validated that Foxp3 levels positively correlated with mTOR signaling pathway activity. The area under the ROC curve for the Treg Foxp3 expression in diagnosing KD was 0.866(95%CI0.794-0.938), with an optimal cutoff value of 0.409, a sensitivity of 94.1%, and a specificity of 72.5%.Conclusion:The expression of Foxp3 in Tregs plays a critical role in the pathogenesis of KD. The decreased level of Foxp3 in children with KD may be associated with the mTORC1-HIF-1α-glycolysis pathway. Foxp3 expression in Tregs may serve as an adjunctive biomarker for the early diagnosis of KD, with significant predictive value.

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