Department of Ophthalmology, Medical Faculty, University Duisburg-Essen, Essen, Germany.
Laboratory of Molecular Ophthalmology, Medical Faculty, University Duisburg-Essen, Essen, Germany.
Endocrine. 2020 May;68(2):265-270. doi: 10.1007/s12020-020-02311-7. Epub 2020 May 12.
Graves' disease (GD) is an autoimmune condition with the appearance of anti-TSH receptor (TSHR) autoantibodies in the serum. The consequence is the development of hyperthyroidism in most of the patients. In addition, in the most severe cases, patients can develop orbitopathy (GO), achropachy and dermopathy. The central role of the TSHR for the disease pathology has been well accepted. Therefore immunization against the TSHR is pivotal for the creation of in vivo models for the disease. However, TSHR is well preserved among the species and therefore the immune system is highly tolerant. Many differing attempts have been performed to break tolerance and to create a proper animal model in the last decades. The most successful have been achieved by introducing the human TSHR extracellular domain into the body, either by injection of plasmid or adenoviruses. Currently available models develop the whole spectrum of Graves' disease-autoimmune thyroid disease and orbitopathy and are suitable to study disease pathogenesis and to perform treatment studies. In recent publications new immunomodulatory therapies have been assessed and also diseaseprevention by inducing tolerance using small cyclic peptides from the antigenic region of the extracellular subunit of the TSHR.
格雷夫斯病（GD）是一种自身免疫性疾病，其血清中出现抗促甲状腺激素受体（TSHR）自身抗体。大多数患者因此发展为甲状腺功能亢进症。此外，在最严重的情况下，患者可能会出现眼病（GO）、杵状指和皮肤病变。TSHR 在疾病发病机制中的核心作用已得到广泛认可。因此，针对 TSHR 的免疫接种对于创建疾病的体内模型至关重要。然而，TSHR 在物种之间保存得很好，因此免疫系统高度耐受。在过去几十年中，人们进行了许多不同的尝试来打破耐受并创建合适的动物模型。最成功的方法是将人 TSHR 细胞外结构域引入体内，无论是通过注射质粒还是腺病毒。目前可用的模型可发展为格雷夫斯病-自身免疫性甲状腺疾病和眼病的全谱，并适合研究疾病发病机制和进行治疗研究。在最近的出版物中，已经评估了新的免疫调节疗法，并且还通过使用 TSHR 细胞外亚基抗原区域的小环状肽来诱导耐受来预防疾病。
