Shuya Kaneko, Fumiaki Sakura, Kay Tanita, A. Shimbo, R. Nambu, Masashi Yoshida, Shuichiro Umetsu, A. Inui, Chizuru Okada, M. Tsumura, Mamiko Yamada, Hisato Suzuki, K. Kosaki, Osamu Ohara, M. Shimizu, Tomohiro Morio, Satoshi Okada, H. Kanegane
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引用次数: 0
摘要
信号转导和激活因子 3(STAT3)基因的基因功能增益(GOF)变异是一种先天性免疫错误,表现为自身免疫和淋巴细胞增殖。该病的症状千差万别,目前尚无有效的治疗方法。本研究调查了 Janus 激酶(JAK)抑制剂(JAKi)对 STAT3-GOF 患者的疗效。研究共招募了四名患者,并描述了他们在开始接受JAKi治疗前后的临床症状。使用从 STAT3-GOF 患者身上提取的 Epstein-Barr 病毒转化淋巴细胞系(EBV-LCLs)进行了细胞刺激试验。患者表现出各种症状,这些症状在开始接受 JAKi 治疗后大多得到了改善。在白细胞介素-6的刺激下,患者的EBV-LCLs与健康对照组的EBV-LCLs相比,STAT3磷酸化增强。总之,四名患有 STAT3-GOF 的日本患者成功地接受了 JAKi 治疗。JAKi改善了患者的各种症状,因此,对STAT3-GOF患者来说,使用JAKi可能是一种有效的治疗选择。
Janus kinase inhibitors ameliorate clinical symptoms in patients with STAT3 gain-of-function
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 were mostly improved after the initiation of JAKi treatment. Upon interleukin-6 stimulation, the EBV-LCLs of patients showed enhanced STAT3 phosphorylation compare 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.