VEXAS syndrome is characterized by inflammasome activation and monocyte dysregulation - Institut Pasteur Access content directly
Journal Articles (Review Article) Nature Communications Year : 2024

VEXAS syndrome is characterized by inflammasome activation and monocyte dysregulation

Marie Templé
Aurélien Corneau
Bénédicte Oules
Pierre Sohier
Roderau Outh
Guillaume Le Guenno
François Lifermann
  • Function : Author
Chloé Friedrich
Cédric Lenormand
Thierry Weitten
Vivien Guillotin
  • Function : Author
Barbara Burroni
  • Function : Author
Jeremy Boussier
Lise Willems
  • Function : Author
Selim Aractingi
  • Function : Author
Léa Dionet
Béatrice Vergier
  • Function : Author
Pierre Raynaud

Abstract

Abstract Acquired 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.
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pasteur-04467897 , version 1 (20-02-2024)

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Olivier Kosmider, Céline Possémé, Marie Templé, Aurélien Corneau, Francesco Carbone, et al.. VEXAS syndrome is characterized by inflammasome activation and monocyte dysregulation. Nature Communications, 2024, 15 (1), pp.910. ⟨10.1038/s41467-024-44811-4⟩. ⟨pasteur-04467897⟩
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