Janus kinase inhibitors ameliorate clinical symptoms in patients with STAT3 gain-of-function-Reference-Cited by-同舟云学术

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

Published:2023-01-01 Issue:1 Volume:3 Page:
ISSN:2732-4303
Container-title:Immunotherapy Advances
language:en
Short-container-title:

Author:

Kaneko Shuya¹,Sakura Fumiaki²,Tanita Kay¹,Shimbo Asami¹,Nambu Ryusuke³,Yoshida Masashi³,Umetsu Shuichiro⁴,Inui Ayano⁴,Okada Chizuru⁵,Tsumura Miyuki²,Yamada Mamiko⁶,Suzuki Hisato⁶^ORCID,Kosaki Kenjiro⁶,Ohara Osamu⁷^ORCID,Shimizu Masaki¹^ORCID,Morio Tomohiro¹^ORCID,Okada Satoshi²^ORCID,Kanegane Hirokazu⁸^ORCID

Affiliation:

1. Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU) , Tokyo , Japan

2. Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences , Hiroshima , Japan

3. Division of Gastroenterology and Hepatology, Saitama Children’s Medical Center , Saitama , Japan

4. Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohama-shi Tobu Hospital , Kanagawa , Japan

5. Hiroshima Chuodori Children Clinic , Hiroshima , Japan

6. Center for Medical Genetics, Keio University School of Medicine , Tokyo , Japan

7. Department of Technology Development, Kazusa DNA Research Institute , Chiba , Japan

8. Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University , Tokyo , Japan

Abstract

Summary 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.

Publisher

Oxford University Press (OUP)

Subject

General Medicine

Link

https://academic.oup.com/immunotherapyadv/advance-article-pdf/doi/10.1093/immadv/ltad027/53788835/ltad027.pdf

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5. Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3;Haapaniemi,2015

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1. JAK inhibitors to treat STAT3 gain-of-function: a single-center report and literature review;Frontiers in Immunology;2024-08-23