VEXAS syndrome: on the threshold of changing perceptions of known diseases DOI Creative Commons
B. D. Chaltsev, А. В. Торгашина, А. М. Лила

et al.

Modern Rheumatology Journal, Journal Year: 2023, Volume and Issue: 17(6), P. 92 - 101

Published: Dec. 20, 2023

This article presents the first case of VEXAS syndrome identified in Russian Federation as well characteristics currently known clinical manifestations and treatment approaches. The observation described is an impressive example how identification a new pathogenic mutation can change understanding classification, diagnosis previously immunoinflammatory diseases. Thus, refractory forms relapsing polychondritis, neutrophilic dermatosis, atypical vasculitis, inflammatory joint diseases or undifferentiated systemic syndrome, especially when associated with macrocytic anemia myelodysplastic should be suspected genetic testing performed to exclude autoinflammatory nature existing condition.

Language: Английский

Mechanisms of hematopoietic clonal dominance in VEXAS syndrome DOI Creative Commons
Raffaella Molteni, Martina Fiumara, Corrado Campochiaro

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Clonal dominance characterizes hematopoiesis during aging and increases susceptibility to blood cancers common nonmalignant disorders. VEXAS syndrome is a recently discovered, adult-onset, autoinflammatory disease burdened by high mortality rate caused dominant hematopoietic clones bearing somatic mutations in the UBA1 gene. However, pathogenic mechanisms driving clonal are unknown. Moreover, lack of models hampers development disease-modifying therapies. In present study, we performed immunophenotype characterization single-cell transcriptomics cohort nine male patients with syndrome, revealing pervasive inflammation across all lineages. Hematopoietic stem progenitor cells (HSPCs) skewed toward myelopoiesis acquire senescence-like programs. Humanized generated inserting causative mutation healthy HSPCs through base editing, recapitulated proteostatic defects, cytological alterations senescence signatures patients' cells, as well hematological inflammatory hallmarks. Competitive transplantations human UBA1-mutant wild-type showed that, although mutant more resilient milieu, probably acquisition state, ones progressively exhausted overwhelmed clones, overall impairing functional leading bone marrow failure. Our study unveils mechanism provides for preclinical studies preliminary insights that could inform therapeutic strategies.

Language: Английский

Citations

1
Update on autoinflammatory diseases DOI

Kosar Asna Ashari,

Jonathan S. Hausmann, Fatma Dedeoğlu

et al.

Current Opinion in Rheumatology, Journal Year: 2023, Volume and Issue: 35(5), P. 285 - 292

Published: July 6, 2023

Purpose of review Although the concept systemic autoinflammatory diseases (SAIDs) is still very young, our knowledge about them exponentially growing. In current review, we aim to discuss novel SAIDs and pathways discovered in last couple years. Recent findings Advances immunology genetics have led discovery new involved autoinflammation, as well several SAIDs, including retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, migraine headache (ROSAH syndrome), vacuoles, E1 enzyme, X-linked somatic (VEXAS) syndrome, TBK1 deficiency, NEMO deleted exon 5 syndrome (NDAS), disabling pansclerotic morphea. Progress immunobiology has also brought forth treatments for SAIDs. Personalized medicine made significant progress areas such cytokine-targeted therapies gene therapies. However, much work remains, especially measuring improving quality life patients with Summary novelties world mechanistic pathogenesis, treatment. We hope this helps rheumatologists gain an updated understanding

Language: Английский

Citations

4
Painful Diplopia as an Initial Presentation of VEXAS Syndrome DOI
Ahmed Zewar,

Caroline A Zollinger-Read,

Lisa Dunkley

et al.

Neuro-Ophthalmology, Journal Year: 2024, Volume and Issue: 48(5), P. 360 - 363

Published: March 12, 2024

This is a case report describing an unusual presentation of acute painful diplopia that led to the diagnosis VEXAS syndrome. (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome adult-onset monogenic auto-inflammatory disease due somatic UBA1 gene mutation in haematopoietic progenitor cells. Our patient was 67-year-old diabetic male who presented with eye movements associated diplopia, left periorbital pain and swelling. Imaging revealed inflammatory process involving multiple intra- extra-orbital structures. The improved initially short course intravenous steroids. However, two months later he re-presented right facial Bone marrow biopsy demonstrated supporting highlights unique ocular VEXAS.

Language: Английский

Citations

1
VEXAS syndrome — long recognised, recently named DOI Open Access
Dorota Suszek, Maciej Dubaj, Aleksandra Dembowska

et al.

Rheumatology Forum, Journal Year: 2023, Volume and Issue: 9(4), P. 186 - 191

Published: Dec. 30, 2023

VEXAS syndrome was first described in 2020. It is a of autoimmune and haematological manifestations caused by somatic mutation the UBA1 gene bone marrow progenitor cells. This results abnormal protein ubiquitination systemic inflammatory process. The main symptoms include recurrent fever, polychondritis, neutrophilic dermatosis, vasculitis, ophthalmic with myelodysplastic syndrome. treatment has proven to be effective high-dose corticosteroids, monoclonal antibodies directed against interleukin 1, 6, tyrosine kinase inhibitors — JAK allogeneic haematopoietic stem-cell transplantation. prognosis unfavourable, many patients do not improve after die.

Language: Английский

Citations

1
Fever, Rash, and Shortness of Breath in a 69-Year-Old DOI
Vivekanand Tiwari, Alexander T. Miller

JAMA, Journal Year: 2024, Volume and Issue: 331(8), P. 698 - 698

Published: Feb. 8, 2024

A 69-year-old had fever, fatigue, rash, right periorbital swelling, and shortness of breath. Chest computed tomography revealed numerous small, bilateral pulmonary nodules; laboratory testing mean corpuscular volume, 96.1 fL; hemoglobin level, 12.4 mg/dL; leukopenia. What is the diagnosis what would you do next?

Language: Английский

Citations

0
Macrocytic Anemia: A Presenting Feature of VEXAS Syndrome DOI

Indira Acharya,

Bernadette Siaton, Christopher Haas

et al.

Annals of Internal Medicine Clinical Cases, Journal Year: 2024, Volume and Issue: 3(6)

Published: June 1, 2024

Language: Английский

Citations

0
VEXAS syndrome: on the threshold of changing perceptions of known diseases DOI Creative Commons
B. D. Chaltsev, А. В. Торгашина, А. М. Лила

et al.

Modern Rheumatology Journal, Journal Year: 2023, Volume and Issue: 17(6), P. 92 - 101

Published: Dec. 20, 2023

This article presents the first case of VEXAS syndrome identified in Russian Federation as well characteristics currently known clinical manifestations and treatment approaches. The observation described is an impressive example how identification a new pathogenic mutation can change understanding classification, diagnosis previously immunoinflammatory diseases. Thus, refractory forms relapsing polychondritis, neutrophilic dermatosis, atypical vasculitis, inflammatory joint diseases or undifferentiated systemic syndrome, especially when associated with macrocytic anemia myelodysplastic should be suspected genetic testing performed to exclude autoinflammatory nature existing condition.

Language: Английский

Citations

0