Ueta Mayumi, Nishigaki Hiromi, Yoshioka Hokoru, Kinoshita Shigeru, Sotozono Chie
Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajiicho, Hirokoji, Kawaramachi, Kamigyoku, Kyoto, 602-0841, Japan.
Sci Rep. 2025 Jan 6;15(1):893. doi: 10.1038/s41598-025-85528-8.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous disorders characterized by extensive tissue necrosis; they are often accompanied by severe ocular complications (SOC). The regulatory role of microRNAs (miRNAs) in modulating immune responses in SJS/TEN is not fully understood, particularly in relation to chronic SOC. We explored the expression profiles of specific miRNAs and their potential impact on the regulation of key innate immune genes in patients with SJS/TEN with SOC. We analyzed plasma samples from 100 patients with chronic stage SJS/TEN with SOC and 92 healthy controls to examine the expression levels of eight specific miRNAs (let-7a-5p, let-7d-3p, let-7e-5p, miR-146a-5p, miR-130a-3p, miR-151a-3p, miR-151a-5p, miR-27b-3p) using quantitative RT-PCR (RT-qPCR). In addition, we subjected mononuclear cells from 12 SJS/TEN patients and 9 controls to RT-qPCR to assess the expression of the innate immune-related genes IFI44L, TNFSF10, AIM2, RSAD2, CXCL10, TRIM22, IFI27, and IFIT2. Significant upregulation of 4 miRNAs (let-7a-5p, let-7e-5p, miR-146a-5p, and miR-27b-3p) was observed in the plasma of SJS/TEN patients; this correlated with the increased expression of TLR3, RIG-I, and MDA5. Furthermore, MDA5, IFI44L, RSAD2, CXCL10, and IFIT2 were also significantly up-regulated in the mononuclear cells from these patients, indicating a systemic modulation of immune response genes. Our findings demonstrate that specific miRNAs are up-regulated in SJS/TEN with SOC and associated with the upregulation of critical immune response genes, suggesting their involvement in the pathogenesis and persistence of SOC. These miRNAs and their target genes may serve as potential biomarkers or therapeutic targets in managing SJS/TEN with SOC.
史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）是严重的黏膜皮肤疾病，其特征为广泛的组织坏死；它们常伴有严重的眼部并发症（SOC）。微小RNA（miRNA）在调节SJS/TEN免疫反应中的作用尚未完全明确，尤其是与慢性SOC相关的作用。我们探究了特定miRNA的表达谱及其对患有SOC的SJS/TEN患者关键固有免疫基因调控的潜在影响。我们分析了100例患有慢性期SJS/TEN并伴有SOC的患者以及92例健康对照者的血浆样本，使用定量逆转录聚合酶链反应（RT-qPCR）检测8种特定miRNA（let-7a-5p、let-7d-3p、let-7e-5p、miR-146a-5p、miR-130a-3p、miR-151a-3p、miR-151a-5p、miR-27b-3p）的表达水平。此外，我们对12例SJS/TEN患者和9例对照者的单核细胞进行RT-qPCR，以评估固有免疫相关基因IFI44L、TNFSF10、AIM2、RSAD2、CXCL10、TRIM22、IFI27和IFIT2的表达。在SJS/TEN患者血浆中观察到4种miRNA（let-7a-5p、let-7e-5p、miR-146a-5p和miR-27b-3p）显著上调；这与TLR3、RIG-I和MDA5表达增加相关。此外，这些患者单核细胞中的MDA5、IFI44L、RSAD2、CXCL10和IFIT2也显著上调，表明免疫反应基因存在全身性调节。我们的研究结果表明，特定miRNA在伴有SOC的SJS/TEN中上调，并与关键免疫反应基因的上调相关，提示它们参与了SOC的发病机制和持续存在。这些miRNA及其靶基因可能作为管理伴有SOC的SJS/TEN的潜在生物标志物或治疗靶点。
