Gene expression analysis in endothelial cells derived from patients with Autosomal-dominant hyper-IgE syndrome (AD-HIES). Gene expression analysis in endothelial cells derived from patients with Autosomal-dominant hyper-IgE syndrome (AD-HIES)

Autosomal-dominant hyper-IgE syndrome (AD-HIES, Job’s syndrome) is a primary immunodeficiency caused by loss of function mutations in signal transducer and activator of transcription 3 (STAT3), a critical regulator of diverse cellular processes. In addition to immunological deficits, patients experience severe non-immunological features including skeletal, connective tissue and vascular abnormalities, poor post-infection healing, and subsequent pulmonary failure. The underlying mechanisms of these STAT3-dependent non-immunological features are not understood, preventing the development of targeted treatments. In this study, global gene expression was analysed in the patients umbilical vein endothelial cells in order to identify signaling pathway affected by the disease-causing STAT3 mutations with ultimate goal to better understand the disease mechanism and identify promising therapeutic targets. Overall design: Cultured endothelial cells isolated from umbilical cords of 3 babies with AD-HIES STAT3 mutations and from 3 control cords were treated with or without TNFα for 8h and mRNA expression profiles were analyzed by RNA-Seq. **RAW data not provided due to patient privacy concerns**

常染色体显性高IgE综合征（Autosomal-dominant hyper-IgE syndrome, AD-HIES，又称Job综合征）是一类原发性免疫缺陷病，由信号转导与转录激活因子3（signal transducer and activator of transcription 3, STAT3）的功能丧失性突变引发，而STAT3是调控多种细胞过程的关键因子。除免疫功能缺陷外，患者还会出现严重的非免疫相关临床表现，包括骨骼、结缔组织与血管异常、感染后愈合不良，以及后续的肺功能衰竭。目前这类STAT3依赖型非免疫表型的潜在发病机制尚不明确，这阻碍了针对性治疗手段的开发。本研究对患者的脐静脉内皮细胞开展全基因表达分析，旨在明确致病STAT3突变所影响的信号通路，最终目标是加深对该疾病发病机制的理解，并筛选出具有潜力的治疗靶点。整体实验设计：从3名携带AD-HIES相关STAT3突变的婴儿脐带中分离培养内皮细胞，同时以3份健康对照脐带来源的内皮细胞作为对照；两组细胞均分别经TNFα处理或不做处理，培养8小时后，通过RNA测序（RNA-Seq）分析mRNA表达谱。**因患者隐私保护问题，原始数据暂不提供**