To the Editor:Aging is characterized by progressive functional decline,with the gradual loss of proteostasis being a widely acknowledged hallmark of the aging process.Direct evidence indicates a reduction in ubiquitin...To the Editor:Aging is characterized by progressive functional decline,with the gradual loss of proteostasis being a widely acknowledged hallmark of the aging process.Direct evidence indicates a reduction in ubiquitination levels in aged worms1.Therefore,the development of therapeutics that target the ubiquitination pathways could offer substantial potential for delaying the onset of aging or age-related diseases.展开更多
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
基金supported by the Science and Technology Commission of Shanghai Municipality(No.22Y11906200,China)Shanghai First Maternity and Infant Hospital(No.2019RC06,China)the National Natural Science Foundation of China(Nos.32171288 and 32471341).
文摘To the Editor:Aging is characterized by progressive functional decline,with the gradual loss of proteostasis being a widely acknowledged hallmark of the aging process.Direct evidence indicates a reduction in ubiquitination levels in aged worms1.Therefore,the development of therapeutics that target the ubiquitination pathways could offer substantial potential for delaying the onset of aging or age-related diseases.
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。
