Human inherited complete STAT2 deficiency underlies inflammatory viral diseases.
J Clin Invest
; 133(12)2023 06 15.
Article
em En
| MEDLINE
| ID: mdl-36976641
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
/
Viroses
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Encefalite por Herpes Simples
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Influenza Humana
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COVID-19
Tipo de estudo:
Prognostic_studies
Limite:
Child, preschool
/
Humans
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Bélgica