VEXAS syndrome in myelodysplastic syndrome with autoimmune disorder

Abstract

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly-described adult-onset inflammatory syndrome characterized by vacuoles in myeloid and erythroid precursor cells and somatic mutations affecting methionine-41 (p.Met41) in UBA1. The VEXAS syndrome often overlaps with myelodysplastic syndromes (MDS) with autoimmune disorders (AD). By screening the UBA1 gene sequences derived from MDS patients with AD from our center, we identified one patient with a p.Met41Leu missense mutation in UBA1, who should have been diagnosed as MDS comorbid with VEXAS syndrome. This patient respond poorly to immune suppressive drugs. Patients with MDS and AD who have characteristic vacuoles in myeloid and erythroid precursor cells should be screened for UBA1 mutation, these patients are likely to have VEXAS syndrome and unlikely to improve with immunosuppressive drugs and should be considered for other alternative therapies.

Keywords: Autoimmune disorders; Cytoplasmic vacuolation; Myelodysplastic syndromes; UBA1 mutation; VEXAS syndrome.

Fig. 1

The mutational profile of myelodysplastic syndromes (MDS) patients with autoimmune disorders (AD) and the mutant site and bone marrow aspirate smears of the patient who had a UBA1 mutation.a Mean numbers of gene mutations (showed by mean and SD) and b mutational profile in MDS patients with and without AD. c Chromatograms of UBA1 somatic variant detected in one MDS patient. d The representative bone marrow aspirate smears of the patient with UBA1 mutation showing dysplasia and characteristic cytoplasmic vacuolation of myeloid and erythroid precursors. The black arrows point to common dysplasia including nuclear abnormalities of erythroid precursor cells and the multinucleated micro-megakaryocyte. The red arrows point to cytoplasmic vacuolation of myeloid and erythroid precursors