Human inherited complete STAT2 deficiency underlies inflammatory viral diseases.
Human inherited complete STAT2 deficiency underlies inflammatory viral diseases.
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DOI：
10.1172/jci168321
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发表时间：
2023-06-15
影响因子：
15.9
通讯作者：
Meyts, Isabelle
中科院分区：
文献类型：
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作者：
Bucciol, Giorgia;Moens, Leen;Ogishi, Masato;Rinchai, Darawan;Matuozzo, Daniela;Momenilandi, Mana;Kerrouche, Nacim;Cale, Catherine M.;Treffeisen, Elsa R.;Al Salamah, Mohammad;Al-Saud, Bandar K.;Lachaux, Alain;Duclaux-Loras, Remi;Meignien, Marie;Bousfiha, Aziz;Benhsaien, Ibtihal;Shcherbina, Anna;Roppelt, Anna;COVID Human Genetic Effort, C. O. V. I. D. Human Genetic Effort;Gothe, Florian;Houhou-Fidouh, Nadhira;Hackett, Scott J.;Bartnikas, Lisa M.;Maciag, Michelle C.;Alosaimi, Mohammed F.;Chou, Janet;Mohammed, Reem W.;Freij, Bishara J.;Jouanguy, Emmanuelle;Zhang, Shen-Ping;Boisson-Dupuis, Stephanie;Beziat, Vivien;Zhang, Qian;Duncan, Christopher J. A.;Hambleton, Sophie;Casanova, Jean-Laurent;Meyts, Isabelle
STAT2 是由 I 型和 III 型 IFN 激活的转录因子。我们报告了 23 名患有导致常染色体隐性遗传 (AR) 完全 STAT2 缺陷的功能丧失变异的患者。转染突变 STAT2 等位基因的细胞和患者细胞均表现出 IFN 刺激基因的表达受损以及对体外病毒感染的控制受损。儿童早期起的临床表现包括对减毒活病毒疫苗（LAV）的严重不良反应和严重病毒感染，特别是危重流感肺炎、危重COVID-19肺炎和1型单纯疱疹病毒（HSV-1）脑炎。患者表现出各种类型的过度炎症，通常由病毒感染或 LAV 给药后引发，这可能证明在缺乏 STAT2 依赖性 I 型和 III 型 IFN 免疫力的情况下，病毒感染尚未解决。转录组分析显示，循环单核细胞、中性粒细胞和 CD8+ 记忆 T 细胞导致了这种炎症。几名患者在不明原因的发热性疾病期间死于病毒感染或心力衰竭。值得注意的是，死亡率最高发生在幼儿期。这些发现表明 AR 完全 STAT2 缺陷是严重病毒性疾病的基础，并严重影响生存。
STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients’ cells displayed impaired expression of IFN-stimulated genes and impaired control of in vitro viral infections. Clinical manifestations from early childhood onward included severe adverse reaction to live attenuated viral vaccines (LAV) and severe viral infections, particularly critical influenza pneumonia, critical COVID-19 pneumonia, and herpes simplex virus type 1 (HSV-1) encephalitis. The patients displayed various types of hyperinflammation, often triggered by viral infection or after LAV administration, which probably attested to unresolved viral infection in the absence of STAT2-dependent types I and III IFN immunity. Transcriptomic analysis revealed that circulating monocytes, neutrophils, and CD8+ memory T cells contributed to this inflammation. Several patients died from viral infection or heart failure during a febrile illness with no identified etiology. Notably, the highest mortality occurred during early childhood. These findings show that AR complete STAT2 deficiency underlay severe viral diseases and substantially impacts survival.
IFNLR1（一种干扰素 lambda 受体 1）的突变与常染色体显性非综合征性听力损失有关
影响因子：
4
作者：
Gao X;Yuan YY;Lin QF;Xu JC;Wang WQ;Qiao YH;Kang DY;Bai D;Xin F;Huang SS;Qiu SW;Guan LP;Su Y;Wang GJ;Han MY;Jiang Y;Liu HK;Dai P
通讯作者：
Dai P