Table_1_Autoimmune Addison's Disease as Part of the Autoimmune Polyglandular Syndrome Type 1: Historical Overview and Current Evidence.pdf

The autoimmune polyglandular syndrome type 1 (APS1) is caused by pathogenic variants of the autoimmune regulator (AIRE) gene, located in the chromosomal region 21q22.3. The related protein, AIRE, enhances thymic self-representation and immune self-tolerance by localization to chromatin and anchorage to multimolecular complexes involved in the initiation and post-initiation events of tissue-specific antigen-encoding gene transcription. Once synthesized, the self-antigens are presented to, and cause deletion of, the self-reactive thymocyte clones. The clinical diagnosis of APS1 is based on the classic triad idiopathic hypoparathyroidism (HPT)—chronic mucocutaneous candidiasis—autoimmune Addison's disease (AAD), though new criteria based on early non-endocrine manifestations have been proposed. HPT is in most cases the first endocrine component of the syndrome; however, APS1-associated AAD has received the most accurate biochemical, clinical, and immunological characterization. Here is a comprehensive review of the studies on APS1-associated AAD from initial case reports to the most recent scientific findings.

自身免疫性多腺体综合征1型（autoimmune polyglandular syndrome type 1, APS1）由自身免疫调节因子（autoimmune regulator, AIRE）基因的致病变异所致，该基因定位于染色体区域21q22.3。其编码的相关蛋白AIRE可通过定位于染色质并锚定参与组织特异性抗原编码基因转录起始及起始后调控过程的多分子复合物，增强胸腺自身抗原呈递与免疫自身耐受。自身抗原合成后，会被呈递至自身反应性胸腺细胞克隆并诱导其克隆清除。APS1的临床诊断曾以特发性甲状旁腺功能减退症（idiopathic hypoparathyroidism, HPT）—慢性皮肤黏膜念珠菌病—自身免疫性艾迪生病（autoimmune Addison's disease, AAD）这一经典三联征为依据，但目前已提出基于早期非内分泌表现的全新诊断标准。多数情况下，特发性甲状旁腺功能减退症是该综合征最先出现的内分泌表现；不过，与APS1相关的自身免疫性艾迪生病目前已得到最为精准的生化、临床与免疫学特征解析。本文对APS1相关自身免疫性艾迪生病的研究进行了全面综述，涵盖从最初的病例报告直至最新的科研发现。