Unexplained fever with consumptive syndrome in the elderly: two cases of VEXAS syndrome with inflammasome dysregulation.
Clin Exp Immunol
; 218(2): 213-220, 2024 Oct 16.
Article
en En
| MEDLINE
| ID: mdl-39119941
ABSTRACT
The aim of this study is to investigate the inflammasome dysregulation in peripheral blood leukocytes of VEXAS patients. The constitutive and in vitro triggered activation of inflammasome in PBMC and neutrophils was analyzed in two Brazilian patients with typical UBA1 mutations, and compared with healthy donors. Our findings highlight the constitutive activation of caspase-1 in VEXAS leukocytes, accompanied by increased plasma levels of IL-18. Furthermore, upon stimulation of isolated peripheral blood mononuclear cells (PBMC) and neutrophils, we observed not only the exhaustion of NLRP3 and NLRP1/CARD8 pathways in VEXAS PBMC but also a significant increase in NLRP3-mediated NETs release in VEXAS neutrophils. These findings support previous studies on the contribution of the inflammasome to VEXAS pathogenesis, identifying at least two profoundly affected pathways (NLRP3 and NLRP1/CARD8) in VEXAS peripheral blood.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leucocitos Mononucleares
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Interleucina-18
/
Proteínas Adaptadoras de Señalización CARD
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Inflamasomas
/
Proteínas NLR
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Proteína con Dominio Pirina 3 de la Familia NLR
/
Neutrófilos
Límite:
Aged
/
Female
/
Humans
/
Male
País/Región como asunto:
America do sul
/
Brasil
Idioma:
En
Revista:
Clin Exp Immunol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Brasil
Pais de publicación:
Reino Unido