Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium.
Department of Microbiology, Immunology and Transplantation, Laboratory of Adaptive Immunology, KU Leuven, Leuven, Belgium.
Front Immunol. 2023 Mar 20;14:1095595. doi: 10.3389/fimmu.2023.1095595. eCollection 2023.
Autosomal dominant Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations result in an inborn error of immunity characterized by chronic mucocutaneous candidiasis, recurrent viral and bacterial infections, and diverse autoimmune manifestations. Current treatment consists of chronic antifungal therapy, antibiotics for concomitant infections, and immunosuppressive therapy in case of autoimmune diseases. More recently, treatment with Janus kinases 1 and 2 (JAK1/2) inhibitors have shown promising yet variable results. We describe a STAT1 GOF patient with an incidental finding of elevated cardiac troponins, leading to a diagnosis of a longstanding, slowly progressive idiopathic myocarditis, attributed to STAT1 GOF. Treatment with a JAK-inhibitor (baricitinib) mitigated cardiac inflammation on MRI but was unable to alter fibrosis, possibly due to the diagnostic and therapeutic delay, which finally led to fatal arrhythmia. Our case illustrates that myocarditis could be part of the heterogeneous disease spectrum of STAT1 GOF. Given the insidious presentation in our case, a low threshold for cardiac evaluation in STAT1 GOF patients seems warranted.
常染色体显性信号转导子和转录激活因子 1（STAT1）功能获得性（GOF）突变导致先天性免疫缺陷，其特征为慢性黏膜皮肤念珠菌病、复发性病毒和细菌感染以及多种自身免疫表现。目前的治疗包括慢性抗真菌治疗、合并感染的抗生素治疗以及自身免疫性疾病的免疫抑制治疗。最近，Janus 激酶 1 和 2（JAK1/2）抑制剂的治疗显示出有希望但结果各异。我们描述了一位 STAT1 GOF 患者，其偶然发现心肌肌钙蛋白升高，导致诊断为长期、缓慢进展的特发性心肌炎，归因于 STAT1 GOF。使用 JAK 抑制剂（巴瑞替尼）减轻了 MRI 上的心脏炎症，但未能改变纤维化，可能是由于诊断和治疗的延迟，最终导致致命性心律失常。我们的病例表明，心肌炎可能是 STAT1 GOF 异质性疾病谱的一部分。鉴于我们的病例隐匿性表现，似乎有必要对 STAT1 GOF 患者进行心脏评估的门槛降低。
