Samra Simran, Bergerson Jenna R E, Freeman Alexandra F, Turvey Stuart E
Department of Pediatrics, British Columbia Children's Hospital, The University of British Columbia, Vancouver, Canada; Experimental Medicine Program, Department of Medicine, The University of British Columbia, Vancouver, Canada.
Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
J Allergy Clin Immunol. 2025 Feb;155(2):357-367. doi: 10.1016/j.jaci.2024.09.020. Epub 2024 Oct 4.
The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling cascade is an evolutionarily conserved signal transduction pathway that regulates many vital cellular processes, including immune function and hematopoiesis. Human genetic variants that disrupt JAK-STAT signaling are being found to cause a rapidly increasing number of diseases, including both germline-encoded inborn errors of immunity (IEI) and acquired somatic variants, causing a so-called phenocopy of the IEI. Multiple genetic mechanisms are responsible for this growing group of JAK-STAT diseases including loss-of-function, gain-of-function, and dominant negative effects. In this review, we discuss the clinical presentation and pathogenesis of all currently described JAK-STAT defects, as well as provide an overview of the guiding principles to consider in diagnosing and treating these conditions.
Janus激酶-信号转导及转录激活因子（JAK-STAT）信号级联是一条在进化上保守的信号转导途径，可调节许多重要的细胞过程，包括免疫功能和造血作用。目前发现，破坏JAK-STAT信号的人类基因变异会导致越来越多的疾病，包括种系编码的先天性免疫缺陷（IEI）和获得性体细胞变异，后者会导致所谓的IEI表型模拟。多种遗传机制导致了这一不断增加的JAK-STAT疾病群体，包括功能丧失、功能获得和显性负效应。在本综述中，我们讨论了所有目前已描述的JAK-STAT缺陷的临床表现和发病机制，并概述了在诊断和治疗这些疾病时应考虑的指导原则。
