Mavridou Maria, Pearce Simon H
Translational and Clinical Research Institute, Newcastle University, BioMedicine West, Newcastle-upon-Tyne, United Kingdom.
Endocrine Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne, United Kingdom.
Front Immunol. 2025 Feb 28;16:1561455. doi: 10.3389/fimmu.2025.1561455. eCollection 2025.
Autoimmune disorders develop owing to a misdirected immune response against self-antigen. Genetic studies have revealed that numerous variants in genes encoding immune system proteins are associated with the development of autoimmunity. Indeed, many of these genetic variants in key immune receptors or transcription factors are common in the pathogenesis of several different autoimmune conditions. In contrast, the proclivity to develop autoimmunity to any specific target organ or tissue is under-researched. This has particular relevance to autoimmune endocrine conditions, where organ-specific involvement is the rule. Genetic polymorphisms in the genes encoding the targets of autoimmune responses have been shown to be associated with predisposition to several autoimmune diseases, including type 1 diabetes, autoimmune thyroid disease and Addison's disease. Mechanistically, variations leading to decreased intrathymic expression, overexpression, different localisation, alternative splicing or post-translational modifications can interfere in the tolerance induction process. This review will summarise the different ways genetic variations in certain genes encoding endocrine-specific antigens (INS, TSHR, TPO, CYP21A2, PIT-1) may predispose to different autoimmune endocrine conditions.
自身免疫性疾病是由于针对自身抗原的免疫反应错误导向而产生的。遗传学研究表明，编码免疫系统蛋白的基因中的众多变体与自身免疫性疾病的发生有关。事实上，这些关键免疫受体或转录因子中的许多基因变体在几种不同自身免疫性疾病的发病机制中很常见。相比之下，针对任何特定靶器官或组织发生自身免疫的倾向则研究较少。这与自身免疫性内分泌疾病尤其相关，在这类疾病中，器官特异性受累是规律。编码自身免疫反应靶标的基因中的遗传多态性已被证明与多种自身免疫性疾病的易感性有关，包括1型糖尿病、自身免疫性甲状腺疾病和艾迪生病。从机制上讲，导致胸腺内表达降低、过表达、不同定位、可变剪接或翻译后修饰的变异可干扰耐受性诱导过程。本综述将总结编码内分泌特异性抗原（胰岛素、促甲状腺激素受体、甲状腺过氧化物酶、细胞色素P450 21A2、垂体特异性转录因子1）的某些基因中的遗传变异可能导致不同自身免疫性内分泌疾病的不同方式。
