Human inherited complete STAT2 deficiency underlies inflammatory viral diseases.
J Clin Invest
; 133(12)2023 06 15.
Article
in English
| MEDLINE | ID: covidwho-2253194
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia
/
Virus Diseases
/
Encephalitis, Herpes Simplex
/
Influenza, Human
/
COVID-19
Type of study:
Etiology study
/
Prognostic study
Topics:
Vaccines
/
Variants
Limits:
Child, preschool
/
Humans
Language:
English
Year:
2023
Document Type:
Article
Affiliation country:
JCI168321
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