Characterizing VEXAS syndrome in women: Findings from an international multicenter study.

Abstract

VEXAS syndrome is an autoinflammatory disease caused by somatic UBA1 mutations on the X chromosome, predominantly affecting men. To characterize VEXAS syndrome in women and to compare the features of VEXAS syndrome between sexes. We conducted an international, multicenter study, including 12 women and 301 men with genetically confirmed VEXAS syndrome. Data were collected using a standardized case report form. Bone marrow analyses and molecular investigations were performed locally. Clinical features, age at onset, UBA1 mutation type, variant allele frequency, and mortality were comparable between sexes. Acquired X monosomy was found in 6/8 tested women. Additional clonal mutations were present in 3/5 tested women. Three additional UBA1-mutated women without typical inflammation are described separately. VEXAS syndrome affects women with clinical features similar to men, supporting the need for UBA1 testing in women with compatible presentations. X monosomy is common but not universal, suggesting alternative pathogenic mechanisms.