ABSTRACT
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described autoinflammatory syndrome characterized by diffuse inflammatory manifestations, predisposition to hematological malignancy, and an association with a high rate of thrombosis. VEXAS is attributed to somatic mutations in the UBA1 gene in hematopoietic stem and progenitor cells with myeloid restriction in mature forms. The rate of thrombosis in VEXAS patients is approximately 40% in all reported cases to date. Venous thromboembolism predominates thrombotic events in VEXAS. These are classified as unprovoked in etiology, although systemic and vascular inflammation are implicated. Here, we review the clinical and laboratory characteristics in VEXAS that provide insight into the possible mechanisms leading to thrombosis. We present knowledge gaps in the mechanisms and management of VEXAS-associated thromboinflammation and propose areas for future investigation in the field.
Subject(s)
Antiphospholipid Syndrome , Thrombosis , Humans , Inflammation/complications , Inflammation/genetics , Mutation , Syndrome , Thrombosis/genetics , Ubiquitin-Activating Enzymes/geneticsABSTRACT
OBJECTIVES: To determine fluorescently labeled aerolysin (FLAER) binding and glycophosphatidylinositol-anchored protein expression in bone marrow (BM) cells of healthy volunteers and patients with paroxysmal nocturnal hemoglobinuria (PNH) detected in peripheral blood (PB); compare PNH clone size in BM and PB; and detect PNH in BM by commonly used antibodies. METHODS: Flow cytometry analysis of FLAER binding to leukocytes and expression of CD55/CD59 in erythrocytes. Analysis of CD16 in neutrophils and CD14 in monocytes in BM. RESULTS: FLAER binds to all normal BM leukocytes, and binding increases with cell maturation. In PNH, lymphocytic clones are consistently smaller than clones of other BM cells. PNH clones are detectable in mature BM leukocytes with high specificity and sensitivity using common antibodies. CONCLUSIONS: PNH clone sizes measured in mature BM leukocytes and in PB are comparable, making BM suitable for PNH assessment. We further demonstrate that commonly used reagents (not FLAER or CD55/CD59) can reliably identify abnormalities of BM neutrophils and monocytes consistent with PNH cells.
