Janus kinase inhibitors ameliorate clinical symptoms in patients with STAT3 gain-of-function

被引：3

作者：

Kaneko, Shuya ^{[1
]}

Sakura, Fumiaki ^{[2
]}

Tanita, Kay ^{[1
]}

Shimbo, Asami ^{[1
]}

Nambu, Ryusuke ^{[3
]}

Yoshida, Masashi ^{[3
]}

Umetsu, Shuichiro ^{[4
]}

Inui, Ayano ^{[4
]}

Okada, Chizuru ^{[5
]}

Tsumura, Miyuki ^{[2
]}

Yamada, Mamiko ^{[6
]}

Suzuki, Hisato ^{[6
]}

Kosaki, Kenjiro ^{[6
]}

Ohara, Osamu ^{[7
]}

Shimizu, Masaki ^{[1
]}

Morio, Tomohiro ^{[1
]}

Okada, Satoshi ^{[2
]}

Kanegane, Hirokazu ^{[8
]}

机构：

[1] Tokyo Med & Dent Univ TMDU, Grad Sch Med & Dent Sci, Dept Pediat & Dev Biol, Tokyo, Japan

[2] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Pediat, Hiroshima, Japan

[3] Saitama Childrens Med Ctr, Div Gastroenterol & Hepatol, Saitama, Japan

[4] Saiseikai Yokohama Shi Tobu Hosp, Dept Pediat Hepatol & Gastroenterol, Yokohama, Kanagawa, Japan

[5] Hiroshima Chuodori Children Clin, Hiroshima, Japan

[6] Keio Univ, Sch Med, Ctr Med Genet, Tokyo, Japan

[7] Kazusa DNA Res Inst, Dept Technol Dev, Chiba, Japan

[8] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Child Hlth & Dev, 1-5-45 Yushima,Bunkyo Ku, Tokyo 1138519, Japan

来源：

IMMUNOTHERAPY ADVANCES | 2023年 / 3卷 / 01期

关键词：

signal transducer and activator of transcription 3; gain-of-function; Janus kinase inhibitor; tofacitinib; ruxolitinib; lymphoblastoid cell lines;

D O I：

10.1093/immadv/ltad027

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. Graphical Abstract

引用

页数：8

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