VEXAS综合征[空泡(vacuoles)、泛素激活酶E1(E1 enzyme)、X染色体连锁(X-linked)、自身免疫性炎症(autoinflammatory)、体细胞(somatic)综合征]是一种由UBA1基因体细胞突变引起的成人发病、X连锁克隆性自身炎症性疾病,其特征为系统性炎...VEXAS综合征[空泡(vacuoles)、泛素激活酶E1(E1 enzyme)、X染色体连锁(X-linked)、自身免疫性炎症(autoinflammatory)、体细胞(somatic)综合征]是一种由UBA1基因体细胞突变引起的成人发病、X连锁克隆性自身炎症性疾病,其特征为系统性炎症伴血液系统克隆性病变。UBA1突变导致泛素化障碍、蛋白稳态失衡以及炎症信号通路[包括核因子-κB、Janus激酶-信号转导及转录激活因子(Janus kinase-signal transducer and activator of transcription,JAK-STAT)等]的持续激活,是VEXAS综合征发病的核心机制。该病临床表现累及血液系统、皮肤、软骨、呼吸系统等多个系统及组织,具有显著临床异质性。诊断主要依靠典型临床表现结合UBA1突变检测。目前该病的治疗尚无统一标准:糖皮质激素可快速控制炎症,但复发率高;JAK抑制剂、白细胞介素抑制剂及去甲基化药物等靶向治疗有一定效果;异基因造血干细胞移植在合并骨髓增生异常综合征患者中展现出潜在治愈可能。本文旨在系统阐述VEXAS综合征的发病机制、临床特点、诊断策略及治疗研究进展,以期提高临床医师对该病的认知水平,并为未来该病的精准管理提供思路与方向。展开更多
VEXAS(vacuoles,E1 enzyme,X-linked,autoinflammatory,somatic)syndrome is a severe and progressive disease,characterized by clinical features that bridge rheumatologic and hematologic conditions.[1]VEXAS syndrome is a ra...VEXAS(vacuoles,E1 enzyme,X-linked,autoinflammatory,somatic)syndrome is a severe and progressive disease,characterized by clinical features that bridge rheumatologic and hematologic conditions.[1]VEXAS syndrome is a rare condition that was not reported until 2020.[2]Since then,interest among dermatologists,hematologists,and rheumatologists with published works has increased,[3]but none of them reported in the emergency setting,nor have any cases arisen following COVID-19 infection.展开更多
VEXAS syndrome(vacuoles,E1 enzyme,X-linked,autoinflammatory,somatic)is an adult-onset and treatment-refractory inflammatory disease,caused by acquired mutations in UBA1(ubiquitin-like modifier activating enzyme 1),an ...VEXAS syndrome(vacuoles,E1 enzyme,X-linked,autoinflammatory,somatic)is an adult-onset and treatment-refractory inflammatory disease,caused by acquired mutations in UBA1(ubiquitin-like modifier activating enzyme 1),an X-linked gene encoding an E1 enzyme of the ubiquitin-proteasome system.1 The disease occurs predominantly in elderly male patients and has heterogeneous but expanding clinical features that include fever,characteristic vacuoles in hematopoietic precursors,cytopenias,and chondritis.As such,VEXAS patients may be initially diagnosed with relapsing polychondritis,myelodysplastic syndrome,and other syndromes.展开更多
文摘VEXAS综合征[空泡(vacuoles)、泛素激活酶E1(E1 enzyme)、X染色体连锁(X-linked)、自身免疫性炎症(autoinflammatory)、体细胞(somatic)综合征]是一种由UBA1基因体细胞突变引起的成人发病、X连锁克隆性自身炎症性疾病,其特征为系统性炎症伴血液系统克隆性病变。UBA1突变导致泛素化障碍、蛋白稳态失衡以及炎症信号通路[包括核因子-κB、Janus激酶-信号转导及转录激活因子(Janus kinase-signal transducer and activator of transcription,JAK-STAT)等]的持续激活,是VEXAS综合征发病的核心机制。该病临床表现累及血液系统、皮肤、软骨、呼吸系统等多个系统及组织,具有显著临床异质性。诊断主要依靠典型临床表现结合UBA1突变检测。目前该病的治疗尚无统一标准:糖皮质激素可快速控制炎症,但复发率高;JAK抑制剂、白细胞介素抑制剂及去甲基化药物等靶向治疗有一定效果;异基因造血干细胞移植在合并骨髓增生异常综合征患者中展现出潜在治愈可能。本文旨在系统阐述VEXAS综合征的发病机制、临床特点、诊断策略及治疗研究进展,以期提高临床医师对该病的认知水平,并为未来该病的精准管理提供思路与方向。
基金National High Level Hospital Clinical Research Funding(Scientific Research Seed Fund of Peking University First Hospital).
文摘VEXAS(vacuoles,E1 enzyme,X-linked,autoinflammatory,somatic)syndrome is a severe and progressive disease,characterized by clinical features that bridge rheumatologic and hematologic conditions.[1]VEXAS syndrome is a rare condition that was not reported until 2020.[2]Since then,interest among dermatologists,hematologists,and rheumatologists with published works has increased,[3]but none of them reported in the emergency setting,nor have any cases arisen following COVID-19 infection.
基金funded by the National Natural Sciences Foundation of China(No.82271280 to Y.T.82301433 to J.J.W.)+3 种基金Hunan Provincial Natural Science Foundation of China(No.2022JJ40824 to J.J.W.)Scientific Research Project of Hunan Provincial Health Commission(China)(No.B202303070054 to Y.T.)Talents Startup Fund(China)(No.2209090550 to Y.T.),Youth Science Fund(China)(No.2021Q04 to J.J.W.)the Project Program of National Clinical Research Center for Geriatric Disorders of Xiangya Hospital,Central South University,Changsha,China(No.2022LNJJ14 to H.J.Z.).
文摘VEXAS syndrome(vacuoles,E1 enzyme,X-linked,autoinflammatory,somatic)is an adult-onset and treatment-refractory inflammatory disease,caused by acquired mutations in UBA1(ubiquitin-like modifier activating enzyme 1),an X-linked gene encoding an E1 enzyme of the ubiquitin-proteasome system.1 The disease occurs predominantly in elderly male patients and has heterogeneous but expanding clinical features that include fever,characteristic vacuoles in hematopoietic precursors,cytopenias,and chondritis.As such,VEXAS patients may be initially diagnosed with relapsing polychondritis,myelodysplastic syndrome,and other syndromes.
