TNF-α诱导蛋白3(TNFAIP3),通常称为A20,是泛素编辑复合物的组成部分,显着影响免疫调节,凋亡,以及不同免疫反应的启动。A20蛋白的特征在于N末端卵巢肿瘤(OTU)结构域和一系列七个锌指(ZNF)结构域。TNFAIP3基因的突变与各种免疫相关疾病有关,比如Behçet病,多关节幼年特发性关节炎,自身免疫性甲状腺炎,自身免疫性肝炎,和类风湿性关节炎。这些突变会导致一系列症状,包括,但不限于,反复发烧,溃疡,皮疹,肌肉骨骼和胃肠道功能障碍,心血管问题,和呼吸道感染。这些突变大多数是无义(STOP密码子)或移码突变,这通常与免疫功能障碍有关。尽管如此,错义突变也已被鉴定为这些条件的贡献者。这些遗传改变可能会干扰几种生物学途径,特别是NF-κB信号异常和泛素化失调。目前,A20单倍体功能不全没有明确的治疗方法;然而,治疗策略可以缓解患者的症状。这篇综述深入研究了TNFAIP3基因中报道的突变,受影响个体的临床进展,潜在的疾病机制,并简要概述了A20单倍功能不全的可用药物干预措施。TNFAIP3基因的强制性基因检测应在诊断为自身炎症性疾病的患者中进行,以更好地了解遗传基础并指导治疗决策。
TNF-α-induced protein 3 (TNFAIP3), commonly referred to as A20, is an integral part of the ubiquitin-editing complex that significantly influences immune regulation, apoptosis, and the initiation of diverse immune responses. The A20 protein is characterized by an N-terminal ovarian tumor (OTU) domain and a series of seven zinc finger (ZNF) domains. Mutations in the TNFAIP3 gene are implicated in various immune-related diseases, such as Behçet\'s disease, polyarticular juvenile idiopathic arthritis, autoimmune thyroiditis, autoimmune hepatitis, and rheumatoid arthritis. These mutations can lead to a spectrum of symptoms, including, but not limited to, recurrent fever, ulcers, rashes, musculoskeletal and gastrointestinal dysfunctions, cardiovascular issues, and respiratory infections. The majority of these mutations are either nonsense (STOP codon) or frameshift mutations, which are typically associated with immune dysfunctions. Nonetheless, missense mutations have also been identified as contributors to these conditions. These genetic alterations may interfere with several biological pathways, notably abnormal NF-κB signaling and dysregulated ubiquitination. Currently, there is no definitive treatment for A20
haploinsufficiency; however, therapeutic strategies can alleviate the symptoms in patients. This review delves into the mutations reported in the TNFAIP3 gene, the clinical progression in affected individuals, potential disease mechanisms, and a brief overview of the available pharmacological interventions for A20
haploinsufficiency. Mandatory genetic testing of the TNFAIP3 gene should be performed in patients diagnosed with autoinflammatory disorders to better understand the genetic underpinnings and guide treatment decisions.