Department of Neonatology, Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Clinical Institute of Special Laboratory Diagnostics, Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Front Immunol. 2023 Jan 4;13:1033513. doi: 10.3389/fimmu.2022.1033513. eCollection 2022.
Aicardi-Goutières syndrome (AGS) is a genetically determined early-onset progressive encephalopathy caused by mutations leading to overexpression of type I interferon (IFN) and resulting in various clinical phenotypes. A gain-of-function (GOF) mutation in the gene is associated with robust production of type I IFN and activation of the Janus kinase (JAK) signal transducer and activator of the transcription (STAT) pathway, which can cause AGS type 7. We detail the clinical case of an infant who initially presented with pneumonia (PCP), had recurrent respiratory infections, and was later treated with a JAK inhibitor, baricitinib, because of a genetically confirmed GOF mutation in the gene. This spectrum of GOF mutations with overlapping features of hyperinflammation and severe opportunistic infection, which mimics combined immunodeficiency (CID), has not been described before. In this case, therapy with baricitinib effectively blocked IFN-α activation and reduced STAT1 signaling but had no effect on the progression of the neurological disease.
Aicardi-Goutières 综合征（AGS）是一种由导致 I 型干扰素（IFN）过度表达的基因突变引起的遗传性早发性进行性脑病，可导致多种临床表型。基因中的功能获得（GOF）突变与 I 型 IFN 的大量产生和 Janus 激酶（JAK）信号转导和转录激活因子（STAT）通路的激活相关，可导致 AGS 型 7。我们详细介绍了一名婴儿的临床病例，该婴儿最初表现为肺炎（PCP），反复发生呼吸道感染，后来因基因确认的 基因中的 GOF 突变而接受 JAK 抑制剂巴瑞替尼治疗。这种具有重叠的过度炎症和严重机会性感染特征的 GOF 突变谱，类似于联合免疫缺陷（CID），以前尚未描述过。在这种情况下，巴瑞替尼治疗有效地阻断了 IFN-α 的激活并降低了 STAT1 信号，但对神经系统疾病的进展没有影响。
