Janus kinase inhibitors ameliorate clinical symptoms in patients with STAT3 gain-of-function.
Shuya KanekoFumiaki SakuraKay TanitaAsami ShimboRyusuke NambuMasashi YoshidaShuichiro UmetsuAyano InuiChizuru OkadaMiyuki TsumuraMamiko YamadaHisato SuzukiKenjiro KosakiOsamu OharaMasaki ShimizuTomohiro MorioSatoshi OkadaHirokazu KaneganePublished in: Immunotherapy advances (2023)
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.
Keyphrases
- epstein barr virus
- end stage renal disease
- cell proliferation
- ejection fraction
- newly diagnosed
- chronic kidney disease
- diffuse large b cell lymphoma
- peritoneal dialysis
- prognostic factors
- sleep quality
- patient reported outcomes
- combination therapy
- high throughput
- genome wide
- copy number
- dna damage
- oxidative stress
- stem cells
- single cell
- bone marrow
- high resolution