Unexplained fever with consumptive syndrome in the elderly: two cases of VEXAS syndrome with inflammasome dysregulation-Reference-Cited by-同舟云学术

Unexplained fever with consumptive syndrome in the elderly: two cases of VEXAS syndrome with inflammasome dysregulation

Published:2024-08-09 Issue: Volume: Page:
ISSN:0009-9104
Container-title:Clinical and Experimental Immunology
language:en
Short-container-title:

Author:

Mendonça Leonardo Oliveira¹²³,Leal Vinicius N C⁴,Roa Mariela E G V⁴,Barros Samar Freschi³,Kalil Jorge¹³,Pontillo Alessandra⁴^ORCID

Affiliation:

1. Divisão de Imunologia Clínica e Alergia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (USP) , São Paulo , Brazil

2. Divisão de Imunologia Clínica e Alergia, Centro de Doenças Raras e da Imunidade, Rede DASA - Hospital Nove de Julho , São Paulo , Brazil

3. Laboratório de Investigação Médica (LIM)-19, Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (USP) , São Paulo , Brazil

4. Laboratório de Imunogenética, Departamento de Imunologia, Instituto de Ciências Biomédicas (ICB), Universidade de São Paulo (USP) , São Paulo , Brazil

Abstract

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.

Funder

São Paulo Research Foundation

Publisher

Oxford University Press (OUP)

Link

https://academic.oup.com/cei/advance-article-pdf/doi/10.1093/cei/uxae069/59039047/uxae069.pdf

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