A20, encoded by TNFAIP3, is a critical negative regulator of immune activation. A20 is a ubiquitin editing enzyme with multiple domains, each of which mediates or stabilizes a key ubiquitin modification. A20 targets diverse proteins that are involved in pleiotropic immunologic pathways. The complexity of A20-mediated immunomodulation is illustrated by the varied effects of A20 deletion in different cell types and disease models. Clinically, the importance of A20 is highlighted by its extensive associations with human disease. A20 germline variants are associated with a wide range of inflammatory diseases, while somatic mutations promote development of B cell lymphomas. More recently, the discovery of A20 haploinsufficiency (HA20) has provided real world evidence for the role of A20 in immune cell function. Originally described as an autosomal dominant form of Behcet’s disease, HA20 is now considered a complex inborn error of immunity with a broad spectrum of immunologic and clinical phenotypes.

A20 由TNFAIP3编码，是免疫激活的关键负调节因子。A20 是一种具有多个结构域的泛素编辑酶，每个结构域介导或稳定关键的泛素修饰。A20 靶向参与多效性免疫途径的多种蛋白质。A20 缺失对不同细胞类型和疾病模型的不同影响说明了 A20 介导的免疫调节的复杂性。在临床上，A20 与人类疾病的广泛关联凸显了其重要性。A20 种系变异与多种炎症性疾病相关，而体细胞突变则促进 B 细胞淋巴瘤的发展。最近，A20 单倍体不足 (HA20) 的发现为 A20 在免疫细胞功能中的作用提供了真实世界的证据。HA20 最初被描述为白塞氏病的常染色体显性遗传形式，现在被认为是一种复杂的先天性免疫错误，具有广泛的免疫学和临床表型。