Publications by authors named "Daniela Ospina Cardona"
Objective: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a complex immune disorder consequence of somatic UBA1 variants. Most reported pathogenic UBA1 variants are missense or splice site mutations directly impairing the translational start site at p.Met41, with recent studies showing that these variants are frequent causes of recurrent inflammation in older individuals.
View Article and Find Full Text PDFVEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a pleiotropic, severe autoinflammatory disease caused by somatic mutations in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene. To elucidate VEXAS pathophysiology, we performed transcriptome sequencing of single bone marrow mononuclear cells and hematopoietic stem and progenitor cells (HSPCs) from VEXAS patients. HSPCs are biased toward myeloid (granulocytic) differentiation, and against lymphoid differentiation in VEXAS.
View Article and Find Full Text PDFSomatic mutations in UBA1 cause vacuoles, E1 ubiquitin-activating enzyme, X-linked, autoinflammatory somatic (VEXAS) syndrome, an adult-onset inflammatory disease with an overlap of hematologic manifestations. VEXAS syndrome is characterized by a high mortality rate and significant clinical heterogeneity. We sought to determine independent predictors of survival in VEXAS and to understand the mechanistic basis for these factors.
View Article and Find Full Text PDFThe objective of this study is to describe the clinical features and outcomes of patients with the newly defined vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Nine men with somatic mutations in the UBA1 gene were identified; the most frequent variant was p.Met41Thr (7 of 9, 78%).
View Article and Find Full Text PDFSomatic mutations in UBA1 involving hematopoietic stem and myeloid cells have been reported in patients with the newly defined VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Here, we report clinical hematologic manifestations and unique bone marrow (BM) features in 16 patients with VEXAS. All patients were male and had a history of severe autoinflammatory and rheumatologic manifestations and a somatic UBA1 mutation (p.
View Article and Find Full Text PDFArticle Synopsis
- A study identified somatic mutations in the UBA1 gene as the cause of a newly recognized syndrome called VEXAS, which affects a significant portion of patients diagnosed with relapsing polychondritis (RP).
- Of the 92 RP patients tested, 7.6% had UBA1 mutations, with notable differences in clinical features, mortality rates, and accompanying health issues compared to those with typical RP.
- A clinical algorithm was developed to help identify patients with VEXAS among those diagnosed with RP, showing high sensitivity and specificity based on factors like male sex and specific blood test results.
Poulter and colleagues describe a series from the United Kingdom of 10 male patients with VEXAS syndrome, including 2 with novel genetic changes affecting methionine 41 of E1.
View Article and Find Full Text PDFArticle Synopsis
- Adult-onset inflammatory syndromes can exhibit overlapping symptoms, and the study discovered that mutations in ubiquitin-related genes, particularly in UBA1, are linked to these disorders.
- Researchers utilized various methodologies, including exome sequencing and CRISPR technology, to identify mutations in patients with severe inflammatory conditions that typically develop in late adulthood.
- The findings indicate that these mutations lead to a significant change in immune response and could help define a new inflammatory disorder related to genetic abnormalities in UBA1.