Singh Alpana, Chaudhary Rishabh
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, 226025, (U.P.), India.
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, 226025, (U.P.), India.
J Autoimmun. 2025 Jun;154:103425. doi: 10.1016/j.jaut.2025.103425. Epub 2025 Apr 29.
VEXAS (Vacuoles, E1 Enzyme, X-linked, Auto-inflammatory, Somatic) syndrome is a recently identified auto-inflammatory disorder predominantly affecting males over the age of 50. It arises due to somatic mutations in the UBA1 gene, an X-linked gene essential for initiating the ubiquitin-proteasome system, leading to dysregulated protein degradation and immune dysfunction. Clinically, VEXAS presents with a diverse array of inflammatory manifestations, including persistent fever, neutrophilic dermatosis, auricular and nasal chondritis, pulmonary infiltrates, ocular inflammation, and venous thrombosis, along with significant haematological abnormalities such as macrocytic anemia, thrombocytopenia, myeloid and erythroid precursor vacuolization, and bone marrow dysplasia. These systemic complications contribute to high morbidity and mortality. Currently, therapeutic strategies remain largely undefined, with treatment focusing on two primary approaches, which are modulating inflammation through corticosteroids, JAK inhibitors, or IL-6 blockade and targeting the mutant hematopoietic clone or allogeneic hematopoietic stem cell transplantation (AHSCT) therapies. Supportive interventions, including red blood cell and platelet transfusions, erythropoiesis-stimulating agents, thromboprophylaxis, and antimicrobial prophylaxis, are crucial in managing disease-associated complications. This review aims to present a comprehensive analysis of VEXAS syndrome, focusing on its genetic underpinnings, pathophysiology, clinical manifestations, diagnostic criteria, and evolving therapeutic strategies. By integrating current findings from the literature and identifying gaps in ongoing research, this review seeks to equip clinicians and researchers with a comprehensive understanding of VEXAS syndrome. Additionally, it aims to guide future investigations toward refining diagnostic strategies, optimizing therapeutic approaches, and ultimately improving patient care and clinical outcomes.
VEXAS（空泡、E1酶、X连锁、自身炎症性、体细胞）综合征是一种最近发现的自身炎症性疾病，主要影响50岁以上的男性。它是由UBA1基因的体细胞突变引起的，UBA1基因是启动泛素-蛋白酶体系统所必需的X连锁基因，导致蛋白质降解失调和免疫功能障碍。临床上，VEXAS表现出多种炎症表现，包括持续发热、嗜中性皮病、耳和鼻软骨炎、肺部浸润、眼部炎症和静脉血栓形成，以及显著的血液学异常，如大细胞贫血、血小板减少、髓系和红系前体细胞空泡化以及骨髓发育异常。这些全身并发症导致高发病率和死亡率。目前，治疗策略在很大程度上仍不明确，治疗主要集中在两种主要方法上，即通过皮质类固醇、JAK抑制剂或IL-6阻断来调节炎症，以及靶向突变造血克隆或异基因造血干细胞移植（AHSCT）疗法。支持性干预措施，包括红细胞和血小板输注、促红细胞生成剂、血栓预防和抗菌预防，对于管理疾病相关并发症至关重要。本综述旨在对VEXAS综合征进行全面分析，重点关注其遗传基础、病理生理学、临床表现、诊断标准和不断发展的治疗策略。通过整合文献中的当前研究结果并识别正在进行的研究中的差距，本综述旨在使临床医生和研究人员对VEXAS综合征有全面的了解。此外，它旨在指导未来的研究，以完善诊断策略、优化治疗方法，并最终改善患者护理和临床结果。
