VEXAS syndrome is characterized by inflammasome activation and monocyte dysregulation
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Published:2024-01-30
Issue:1
Volume:15
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Kosmider OlivierORCID, Possémé Céline, Templé MarieORCID, Corneau AurélienORCID, Carbone FrancescoORCID, Duroyon Eugénie, Breillat PaulORCID, Chirayath Twinu-Wilson, Oules BénédicteORCID, Sohier PierreORCID, Luka Marine, Gobeaux Camille, Lazaro EstibalizORCID, Outh RoderauORCID, Le Guenno GuillaumeORCID, Lifermann François, Berleur Marie, Le Mene Melchior, Friedrich ChloéORCID, Lenormand CédricORCID, Weitten ThierryORCID, Guillotin Vivien, Burroni Barbara, Boussier JeremyORCID, Willems Lise, Aractingi Selim, Dionet LéaORCID, Tharaux Pierre-LouisORCID, Vergier Béatrice, Raynaud PierreORCID, Ea Hang-Korng, Ménager MickaelORCID, Duffy DarraghORCID, Terrier Benjamin
Abstract
AbstractAcquired mutations in the UBA1 gene were recently identified in patients with severe adult-onset auto-inflammatory syndrome called VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic). However, the precise physiological and clinical impact of these mutations remains poorly defined. Here we study a unique prospective cohort of VEXAS patients. We show that monocytes from VEXAS are quantitatively and qualitatively impaired and display features of exhaustion with aberrant expression of chemokine receptors. In peripheral blood from VEXAS patients, we identify an increase in circulating levels of many proinflammatory cytokines, including IL-1β and IL-18 which reflect inflammasome activation and markers of myeloid cells dysregulation. Gene expression analysis of whole blood confirms these findings and also reveals a significant enrichment of TNF-α and NFκB signaling pathways that can mediate cell death and inflammation. This study suggests that the control of the nflammasome activation and inflammatory cell death could be therapeutic targets in VEXAS syndrome.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference37 articles.
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