Usage Information
Citation Information: J Clin Invest. 2023;133(12):e168321. https://doi.org/10.1172/JCI168321.
Abstract
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.
Authors
Giorgia Bucciol, Leen Moens, Masato Ogishi, Darawan Rinchai, Daniela Matuozzo, Mana Momenilandi, Nacim Kerrouche, Catherine M. Cale, Elsa R. Treffeisen, Mohammad Al Salamah, Bandar K. Al-Saud, Alain Lachaux, Remi Duclaux-Loras, Marie Meignien, Aziz Bousfiha, Ibtihal Benhsaien, Anna Shcherbina, Anna Roppelt, COVID Human Genetic Effort, Florian Gothe, Nadhira Houhou-Fidouh, Scott J. Hackett, Lisa M. Bartnikas, Michelle C. Maciag, Mohammed F. Alosaimi, Janet Chou, Reem W. Mohammed, Bishara J. Freij, Emmanuelle Jouanguy, Shen-Ying Zhang, Stephanie Boisson-Dupuis, Vivien Béziat, Qian Zhang, Christopher J.A. Duncan, Sophie Hambleton, Jean-Laurent Casanova, Isabelle Meyts
Usage data is cumulative from January 2024 through January 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 4,786 | 668 |
| 339 | 206 | |
| Figure | 382 | 5 |
| Table | 238 | 0 |
| Supplemental data | 85 | 30 |
| Citation downloads | 91 | 0 |
| Totals | 5,921 | 909 |
| Total Views | 6,830 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)