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. 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，Job综合征）是一类由信号转导与转录激活因子3（signal transducer and activator of transcription 3, STAT3）功能丧失突变引发的原发性免疫缺陷病，而STAT3是调控多种细胞过程的关键调控因子。除免疫功能缺陷外，患者还会出现多种严重的非免疫相关表型，包括骨骼、结缔组织与血管异常、感染后愈合不良以及继发性肺衰竭。目前此类依赖STAT3的非免疫相关表型的潜在发病机制尚不明确，这阻碍了靶向治疗手段的开发。本研究对患者的脐静脉内皮细胞开展全基因表达分析，旨在识别致病STAT3突变所影响的信号通路，最终目标是深化对该疾病发病机制的理解，并筛选出具有应用前景的治疗靶点。本研究从3名携带AD-HIES相关STAT3突变的婴儿脐带及3份对照脐带中分离培养内皮细胞，分别用或不用肿瘤坏死因子α（TNFα）处理8小时，随后通过RNA测序（RNA-Seq）分析mRNA表达谱。**由于涉及患者隐私，未提供原始测序数据**