Translational and Clinical Research Institute, Immunity and Inflammation Theme, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Royal Victoria Infirmary, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, NE1 4LP, Newcastle upon Tyne, UK.
J Clin Immunol. 2021 Oct;41(7):1446-1456. doi: 10.1007/s10875-021-01118-z. Epub 2021 Aug 26.
STAT2 is distinguished from other STAT family members by its exclusive involvement in type I and III interferon (IFN-I/III) signaling pathways, and its unique behavior as both positive and negative regulator of IFN-I signaling. The clinical relevance of these opposing STAT2 functions is exemplified by monogenic diseases of STAT2. Autosomal recessive STAT2 deficiency results in heightened susceptibility to severe and/or recurrent viral disease, whereas homozygous missense substitution of the STAT2-R148 residue is associated with severe type I interferonopathy due to loss of STAT2 negative regulation. Here we review the clinical presentation, pathogenesis, and management of these disorders of STAT2.
STAT2 与其他 STAT 家族成员的区别在于其仅参与 I 型和 III 型干扰素 (IFN-I/III) 信号通路,以及其作为 IFN-I 信号的正向和负向调节剂的独特行为。这些相反的 STAT2 功能的临床相关性在 STAT2 的单基因疾病中得到了例证。常染色体隐性 STAT2 缺乏导致对严重和/或复发性病毒病的易感性增加,而 STAT2-R148 残基的纯合错义取代与由于 STAT2 负调节丧失导致的严重 I 型干扰素病有关。在这里,我们回顾了这些 STAT2 疾病的临床表现、发病机制和治疗方法。