■T细胞耗竭(Tex)对自身免疫性疾病有益,但它在格雷夫斯病(GD)中的作用,甲状腺自身免疫性疾病,仍然未知。这项研究调查了GD患者中Tex相关基因的表达,以辨别这些基因对GD发病机理和免疫调节的潜在贡献。
■通过基因景观分析,构建了40个Tex相关基因的蛋白质-蛋白质相互作用网络。在GD患者和健康对照(HCs)之间比较mRNA表达水平。无监督聚类将GD病例分类为亚型,揭示基因表达的区别,免疫细胞浸润,和免疫反应。加权基因共表达网络分析和差异基因表达谱分析确定了潜在的治疗靶标。使用来自112名GD患者的血液样品进行候选基因表达的RT-qPCR验证。分析Tex相关基因表达与临床指标的相关性。
■观察到广泛的Tex相关基因相互作用,6个基因在GD患者中显示异常表达。这与非典型免疫细胞浸润和调节有关。聚类分析描绘了两个GD亚型,揭示了基因表达和免疫反应的显着变化。筛选工作确定了用于GD治疗的多种候选药物。Tex相关基因CBL被鉴定用于进一步验证,并显示GD患者的mRNA表达降低,尤其是在复发的情况下。中度至重度甲状腺肿大患者的CBLmRNA表达明显低于无甲状腺肿大患者。此外,CBLmRNA表达与疾病特异性指标促甲状腺激素受体抗体呈负相关。
■Tex相关基因调节GD发病机制,它们的分组有助于亚型分化和治疗靶点的探索。CBL代表GD复发的潜在标志物。
UNASSIGNED: T-cell exhaustion (Tex) can be beneficial in autoimmune diseases, but its role in Graves\' disease (GD), an autoimmune disorder of the thyroid, remains unknown. This study investigated Tex-related gene expression in GD patients to discern the potential contributions of these genes to GD pathogenesis and immune regulation.
UNASSIGNED: Through gene landscape analysis, a protein-protein interaction network of 40 Tex-related genes was constructed. mRNA expression levels were compared between GD patients and healthy control (HCs). Unsupervised clustering categorized GD cases into subtypes, revealing distinctions in gene expression, immune cell infiltration, and immune responses. Weighted gene co-expression network analysis and differential gene expression profiling identified potential therapeutic targets. RT-qPCR validation of candidate gene expression was performed using blood samples from 112 GD patients. Correlations between Tex-related gene expression and clinical indicators were analyzed.
UNASSIGNED: Extensive Tex-related gene interactions were observed, with six genes displaying aberrant expression in GD patients. This was associated with atypical immune cell infiltration and regulation. Cluster analysis delineated two GD subtypes, revealing notable variations in gene expression and immune responses. Screening efforts identified diverse drug candidates for GD treatment. The Tex-related gene CBL was identified for further validation and showed reduced mRNA expression in GD patients, especially in cases of relapse. CBL mRNA expression was significantly lower in patients with moderate-to-severe thyroid enlargement than in those without such enlargement. Additionally, CBL mRNA expression was negatively correlated with the disease-specific indicator thyrotropin receptor antibodies.
UNASSIGNED: Tex-related genes modulate GD pathogenesis, and their grouping aids subtype differentiation and exploration of therapeutic targets. CBL represents a potential marker for GD recurrence.