Falorni Alberto, Brozzetti Annalisa, Calcinaro Filippo, Marzotti Stefania, Santeusanio Fausto
a Department of Internal Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Via E. Dal Pozzo, 06126 Perugia, Italy.
b Department of Internal Medicine, Via E. Dal Pozzo, 06126 Perugia, Italy.
Expert Rev Endocrinol Metab. 2009 Jul;4(4):333-348. doi: 10.1586/eem.09.20.
Autoimmune Addison's disease (AAD) results from the immune-mediated destruction of adrenocortical cells. AAD is a major component of the autoimmune polyendocrine syndromes type 1 (APS 1) and type 2. The adrenal autoimmune process is made evident by the apperance of circulating autoantibodies against the steroidogenic enzyme 21-hydroxylase. Detection of 21-hydroxylase in patients with endocrine autoimmune diseases enables the identification of subjects with preclinical AAD. An impaired response to a corticotrophin stimulation test marks the irreversible stage of preclinical AAD and predicts progression towards clinical AAD in over 80% of cases. APS 1 is caused by mutations of the autoimmune regulator (AIRE) gene, which encodes an activator of transcription, Aire, that induces the expression of autoantigens in thymic medullary epithelial cells and promotes immunological tolerance. Isolated and APS 2-related AAD is an autoimmune disease with evidence for complex genetic susceptibility caused by T-cell-mediated destruction of adrenocortical cells, with a major contribution of HLA genes. The target cells in the adrenal cortex participate in the immune reaction by releasing chemokines, such as CXCL-10, that attract Th1 cells.
自身免疫性 Addison 病(AAD)是由肾上腺皮质细胞的免疫介导性破坏所致。AAD 是自身免疫性多内分泌综合征 1 型(APS 1)和 2 型的主要组成部分。肾上腺自身免疫过程通过出现针对类固醇生成酶 21 - 羟化酶的循环自身抗体得以显现。在内分泌自身免疫性疾病患者中检测 21 - 羟化酶,能够识别出临床前 AAD 患者。促肾上腺皮质激素刺激试验反应受损标志着临床前 AAD 的不可逆阶段,并预测超过 80%的病例会进展为临床 AAD。APS 1 由自身免疫调节因子(AIRE)基因突变引起,该基因编码一种转录激活因子 Aire,它可诱导胸腺髓质上皮细胞中自身抗原的表达并促进免疫耐受。孤立性及与 APS 2 相关的 AAD 是一种自身免疫性疾病,有证据表明其遗传易感性复杂,是由 T 细胞介导的肾上腺皮质细胞破坏所致,其中 HLA 基因起主要作用。肾上腺皮质中的靶细胞通过释放趋化因子(如 CXCL - 10)参与免疫反应,这些趋化因子可吸引 Th1 细胞。