Blood Podcast VEXAS: A Newly Identified Adult-onset Hemato-inflammatory Syndrome
Jul 1, 2021
This discussion dives deep into VEXAS syndrome, a newly recognized adult-onset inflammatory condition linked to UBA1 mutations. It details how these mutations disrupt cellular processes and lead to severe symptoms. Listeners learn about the distinct inflammatory signatures and histological features of the syndrome. The conversation also explores its prevalence, recommended tests, and potential treatments like cyclosporine and JAK inhibitors. The talk highlights the ongoing mysteries surrounding VEXAS biology, paving the way for future research.
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UBA1 Mutation Links Inflammation And Hematology
- UBA1 encodes the major ubiquitin-activating enzyme and its mutation links inflammation with hematologic disease.
- Mutations reduce cytoplasmic UBA1 function and drive myeloid-intrinsic inflammation via TNF, IL-6, and IFN-γ pathways.
Myeloid-Restricted Mutation With Progenitor Mosaicism
- Mutant UBA1 is enriched in myeloid cells while absent from mature lymphocytes, with mosaicism in early progenitors.
- This suggests mutant lymphocytes fail to survive cellular stress, concentrating pathology in the myeloid lineage.
Characteristic Vacuoles And Clinical Profile
- VEXAS shows vacuoles in myeloid and erythroid precursors composed of lipid droplets and degenerating organelles.
- Clinical features combine late-onset systemic inflammation with macrocytic anemia, cytopenias, chondritis, and skin involvement.