VEXAS Syndrome

VEXAS syndrome is a monogenic disease of adulthood caused by somatic mutations in UBA1 in hematopoietic progenitor cells. Patients present with a range of inflammatory and hematologic symptoms (Visual Abstract). Myeloid-driven autoinflammation and progressive bone marrow failure lead to substantial morbidity and mortality. Effective medical treatments, beyond glucocorticoids, need to be identified. Reports in the current issue of Blood describe novel UBA1 genetic variants, treatment options, and insight into disease pathophysiology. VEXAS syndrome represents a prototype for a new class of diseases.