PDF(Pubmed)
Abstract：
Germline gain-of-function (GOF) variants in the signal transducer and activator of transcription 3 (STAT3) gene is an inborn error of immunity presenting with autoimmunity and lymphoproliferation. Symptoms can vary widely, and no effective treatment has been established. This study investigated the efficacy of Janus kinase (JAK) inhibitors (JAKi) in patients with STAT3-GOF. Four patients were enrolled and their clinical symptoms before and after the initiation of treatment with JAKi were described. A cell stimulation assay was performed using Epstein-Barr virus transformed lymphoid cell lines (EBV-LCLs) that were derived from the patients with STAT3-GOF. The patients presented with various symptoms, and these symptoms mostly improved after the initiation of JAKi treatment. Upon interleukin-6 stimulation, the EBV-LCLs of patients showed enhanced STAT3 phosphorylation compared with those of the EBV-LCLs of healthy controls. In conclusion, four Japanese patients with STAT3-GOF were successfully treated with JAKi. JAKi ameliorated various symptoms and therefore, the use of JAKi could be an effective treatment option for patients with STAT3-GOF.
摘要：
信号转导和转录激活因子3（STAT3）基因中的种系功能获得（GOF）变体是一种先天性免疫错误，表现为自身免疫和淋巴增生。症状可能差异很大，没有建立有效的治疗方法。这项研究调查了Janus激酶（JAK）抑制剂（JAKi）在STAT3-GOF患者中的疗效。纳入4例患者，描述了他们在开始JAKi治疗前后的临床症状。使用来源于患有STAT3-GOF的患者的Epstein-Barr病毒转化的淋巴样细胞系(EBV-LCLs)进行细胞刺激测定。患者出现各种症状，这些症状大多在开始JAKI治疗后得到改善。在白细胞介素-6刺激下，与健康对照组的EBV-LCL相比,患者的EBV-LCL显示STAT3磷酸化增强.总之,4例日本STAT3-GOF患者成功接受JAKI治疗.JAKI改善了各种症状，因此，对于STAT3-GOF患者,使用JAKI可能是一种有效的治疗选择.
