Independent mechanisms of inflammation and myeloid bias in VEXAS syndrome.

ABSTRACT: Somatically acquired mutations in the E1 ubiquitin-activating enzyme UBA1 within haematopoietic stem and progenitor cells (HSPCs) were recently identified as the cause of the adult-onset autoinflammatory syndrome VEXAS (vacuoles, E1 enzyme, X linked, autoinflammatory, somatic)¹. UBA1 mutations in VEXAS lead to clonal expansion within the HSPC and myeloid, but not lymphoid, compartments. Despite its severity and prevalence, the mechanisms by which UBA1 mutations cause multiorgan autoinflammation and haematological disease are unclear. Here we use somatic gene-editing approaches to model VEXAS-associated UBA1 mutations in primary macrophages and HSPCs. Uba1-mutant mouse macrophages exposed to inflammatory stimuli underwent aberrant apoptotic and necroptotic cell death mediated by

SUBMITTER: Narendra VK 

PROVIDER: S-EPMC12851934 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature