Fiumara Martina, Molteni Raffaella, Scorpio Gianluca, Tomelleri Alessandro, Bergonzi Gregorio Maria, Ferrari Samuele, Matucci-Cerinic Marco, Cenci Simone, Dagna Lorenzo, Ciceri Fabio, Diral Elisa, Campochiaro Corrado
San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Expert Rev Hematol. 2025 Jul;18(7):509-519. doi: 10.1080/17474086.2025.2508505. Epub 2025 May 30.
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an acquired autoinflammatory disorder caused by somatic mutations in the UBA1 gene. Predominantly affecting males over 50, the disease presents with systemic inflammation, hematologic abnormalities, and features of clonal hematopoiesis, with nearly half of patients developing myelodysplastic syndromes (MDS). The interaction between inflammation and clonal expansion defines disease progression, emphasizing the need for a comprehensive understanding of its pathogenesis and management.
This review discusses the clinical spectrum, genetic landscape, and pathogenic mechanisms of VEXAS syndrome. The correlation between UBA1 mutations and disease severity is explored, alongside the role of clonal hematopoiesis and inflammatory pathways. Current treatments, including corticosteroids, immunosuppressants, JAK inhibitors, and azacitidine, are evaluated for efficacy and limitations. The potential of allogeneic hematopoietic stem cell transplantation (allo-HSCT) as a curative approach is also addressed. Literature search was conducted from January 2020 to present using PubMed and Scopus databases to identify relevant studies.
VEXAS syndrome reflects a complex interaction between autoinflammation and clonal hematopoiesis. While targeted therapies offer symptomatic control, responses remain variable. Future strategies should focus on genotype-driven, personalized treatments and optimizing allo-HSCT protocols to improve patient outcomes and offer disease-modifying potential.
VEXAS（空泡、E1酶、X连锁、自身炎症性、体细胞）综合征是一种由UBA1基因体细胞突变引起的后天性自身炎症性疾病。该疾病主要影响50岁以上男性，表现为全身炎症、血液学异常以及克隆性造血特征，近一半患者会发展为骨髓增生异常综合征（MDS）。炎症与克隆性扩增之间的相互作用决定了疾病的进展，这凸显了全面了解其发病机制和治疗方法的必要性。
本综述讨论了VEXAS综合征的临床谱、遗传格局和致病机制。探讨了UBA1突变与疾病严重程度之间的相关性，以及克隆性造血和炎症途径的作用。对包括皮质类固醇、免疫抑制剂、JAK抑制剂和阿扎胞苷在内的当前治疗方法的疗效和局限性进行了评估。还讨论了异基因造血干细胞移植（allo-HSCT）作为一种治愈方法的潜力。使用PubMed和Scopus数据库从2020年1月至今进行文献检索，以确定相关研究。
VEXAS综合征反映了自身炎症与克隆性造血之间的复杂相互作用。虽然靶向治疗可提供症状控制，但反应仍存在差异。未来的策略应侧重于基因型驱动的个性化治疗，并优化allo-HSCT方案，以改善患者预后并提供疾病修饰潜力。
