Independent mechanisms of inflammation and myeloid bias in VEXAS syndrome

VEXAS syndrome research reveals overactive bone marrow stem cells may drive inflammation

Researchers at Memorial Sloan Kettering Cancer Center (MSK) have developed some of the first robust laboratory models of a confounding adult-onset inflammatory disease called VEXAS syndrome—shedding new light on its mechanisms and laying the groundwork for potential targeted treatments.

Independent mechanisms of inflammation and myeloid bias in VEXAS syndrome

Somatically acquired mutations in the E1 ubiquitin-activating enzyme UBA1 within hematopoietic 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 whereby …

JCI Neutrophils take center stage in VEXAS syndrome pathogenesis

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an adult-onset inflammatory disorder caused by somatic UBA1 mutations in hematopoietic stem cells. UBA1 encodes a key enzyme that catalyzes protein ubiquitination. Clinically, VEXAS is characterized by systemic inflammation and hematologic abnormalities. Patient studies have hinted that the transition of UBA1-mutated stem cells into proinflammatory myeloid precursors ma…