1. Unexplained fever with consumptive syndrome in the elderly: two cases of VEXAS syndrome with inflammasome dysregulation.
- Author
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Mendonça LO, Leal VNC, Roa MEGV, Barros SF, Kalil J, and Pontillo A
- Subjects
- Humans, Female, Male, Caspase 1 genetics, Aged, Adaptor Proteins, Signal Transducing genetics, Apoptosis Regulatory Proteins genetics, Ubiquitin-Activating Enzymes genetics, Fever immunology, Mutation, Brazil, Neoplasm Proteins, Inflammasomes metabolism, Inflammasomes immunology, Inflammasomes genetics, NLR Family, Pyrin Domain-Containing 3 Protein genetics, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Interleukin-18 blood, Interleukin-18 genetics, CARD Signaling Adaptor Proteins genetics, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, NLR Proteins genetics, Neutrophils immunology
- 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
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