Decoding VEXAS syndrome: emerging insights into pathogenesis and clinical management
Martina Fiumara1,2, Corrado Campochiaro2,3, Raffaella Molteni2,4
1San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute.
Current Opinion in Rheumatology
|November 1, 2025
Summary
VEXAS syndrome, a somatic UBA1 mutation-driven disease, involves inflammatory hematopoietic cells that impair normal blood cell development. Current guidelines offer strategies to manage VEXAS, improving patient outcomes.
Area of Science:
- Hematology
- Immunology
- Genetics
Background:
- VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory disease.
- It is characterized by clonal dominance of pro-inflammatory hematopoietic cells with a somatic UBA1 gene mutation.
Purpose of the Study:
- To review and synthesize recent advancements in understanding VEXAS syndrome pathogenesis.
- To discuss current clinical management strategies for VEXAS syndrome.
Main Methods:
- Literature review integrating recent findings.
- Analysis of molecular mechanisms and clinical guidelines.
Main Results:
- VEXAS pathogenesis involves an interplay between inflammation and clonal dominance of UBA1 mutant hematopoietic cells.
- Mutant cells create an inflammatory environment impairing wild-type hematopoiesis and exhibit pro-survival pathways.
- Recent international guidelines provide evidence-based recommendations for managing inflammatory and hematologic features.
Conclusions:
- Understanding VEXAS pathobiology is advancing through dissecting molecular drivers of inflammation and clonal survival.
- Current therapeutic strategies aim to counteract disease progression and improve patient outcomes.
- Future research will enable more precise, mechanism-driven treatments for VEXAS syndrome.
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