Human inherited complete STAT2 deficiency underlies inflammatory viral diseases.
Author
Bucciol, GiorgiaMoens, 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
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-Ying
Boisson-Dupuis, Stephanie
Béziat, Vivien
Zhang, Qian
Duncan, Christopher Ja
Hambleton, Sophie
Casanova, Jean-Laurent
Meyts, Isabelle
Publication date
2023-06-15Subject
Microbiology. Immunology
Metadata
Show full item recordAbstract
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.Citation
Bucciol G, Moens L, Ogishi M, Rinchai D, Matuozzo D, Momenilandi M, Kerrouche N, Cale CM, Treffeisen ER, Al Salamah M, Al-Saud BK, Lachaux A, Duclaux-Loras R, Meignien M, Bousfiha A, Benhsaien I, Shcherbina A, Roppelt A; COVID Human Genetic Effort; Gothe F, Houhou-Fidouh N, Hackett SJ, Bartnikas LM, Maciag MC, Alosaimi MF, Chou J, Mohammed RW, Freij BJ, Jouanguy E, Zhang SY, Boisson-Dupuis S, Béziat V, Zhang Q, Duncan CJ, Hambleton S, Casanova JL, Meyts I. Human inherited complete STAT2 deficiency underlies inflammatory viral diseases. J Clin Invest. 2023 Jun 15;133(12):e168321. doi: 10.1172/JCI168321. PMID: 36976641; PMCID: PMC10266780.Type
ArticleAdditional Links
https://www.jci.org/PMID
36976641ae974a485f413a2113503eed53cd6c53
10.1172/JCI168321