DataSheet_1_Single-cell RNA sequencing combined with whole exome sequencing reveals the landscape of the immune pathogenic response to chronic mucocutaneous candidiasis with STAT1 GOF mutation.pdf

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections with Candida of the skin, nails, and mucous membranes (e.g., mouth, esophagus, and vagina). Compared with that of other infectious diseases, the immune pathogenic mechanism of CMC is still poorly understood. We identified a signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutation in a CMC patient. Single-cell transcriptional profiling on peripheral blood mononuclear cells from this patient revealed decreases in immature B cells and monocytes. Further analysis revealed several differentially expressed genes related to immune regulation, including RGS1, TNFAIP3, S100A8/A9, and CTSS. In our review of the literature on signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutations, we identified seven cases in total. The median age of onset for CMC (n=4, data lacking for three cases) was 10.5 years (range: birth to 11 years), with an average onset age of 8 years. There were no reports linking tumors to the c.Y289C mutation, and the incidence of pre-existing clinical disease in patients with the c.Y289C mutation was similar to previous data.

慢性黏膜皮肤念珠菌病（Chronic mucocutaneous candidiasis, CMC）以皮肤、指甲及黏膜（如口腔、食管、阴道）反复或持续性念珠菌感染为特征。相较于其他传染病，慢性黏膜皮肤念珠菌病的免疫致病机制目前仍不甚明确。本研究在1例慢性黏膜皮肤念珠菌病患者体内鉴定出信号转导与转录激活因子1（signal transducer and activator of transcription 1, STAT1）功能获得型（c.Y289C）突变。对该患者外周血单个核细胞开展单细胞转录谱分析后发现，未成熟B细胞与单核细胞占比显著降低。进一步的分析揭示了多个与免疫调控相关的差异表达基因，包括RGS1、TNFAIP3、S100A8/A9及CTSS。在针对信号转导与转录激活因子1功能获得型（c.Y289C）突变的文献回顾中，本研究共确定7例病例。慢性黏膜皮肤念珠菌病的发病中位年龄（有效病例n=4，其余3例数据缺失）为10.5岁（范围：出生至11岁），平均发病年龄为8岁。目前尚无肿瘤与c.Y289C突变相关的报道，且携带该突变患者的基础临床疾病发生率与既往研究数据相近。