Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
Autoimmun Rev. 2013 Jul;12(9):875-84. doi: 10.1016/j.autrev.2013.03.007. Epub 2013 Mar 25.
The thymus plays distinct roles in the pathogenesis of the different Myasthenia gravis (MG) subtypes. Inflammatory, neoplastic and age-related alterations of the thymus are of pivotal relevance for the initiation of anti-acetylcholine receptor (AChR) autoimmunity in early onset MG, thymoma-associated MG and, likely, late onset MG, respectively. By contrast, the thymus is presumably not related to MG that is due to autoantibodies to the muscle specific kinase, MuSK. Finally, the role of the thymus is still obscure in MG defined by antibodies against the agrin receptor LRP4 and in MG without all of the above autoantibdies (triple sero-negative MG) since these MG subtypes have been described only recently and thymectomy has not been their standard treatment. This review aims to give an update on intrathymic mechanisms of tolerance breakdown in MG, including abnormal T cell selection and activation, the role of thymic myoid cells, the autoimmune regulator (AIRE) and regulatory T cells.
胸腺在不同重症肌无力 (MG) 亚型的发病机制中发挥着不同的作用。胸腺的炎症、肿瘤和与年龄相关的改变，对于早期发病的 MG、胸腺瘤相关的 MG 以及可能的迟发性 MG 中抗乙酰胆碱受体 (AChR) 自身免疫的启动至关重要。相比之下，胸腺与由肌肉特异性激酶 (MuSK) 自身抗体引起的 MG 可能没有关系。最后，由于这些 MG 亚型是最近才被描述的，胸腺切除术也不是它们的标准治疗方法，因此在由抗 agrin 受体 LRP4 抗体和无上述所有自身抗体定义的 MG（三重血清阴性 MG）中，胸腺的作用仍然不清楚。本文旨在对 MG 中胸腺内耐受破坏的机制进行综述，包括异常 T 细胞的选择和激活、胸腺肌样细胞、自身免疫调节因子 (AIRE) 和调节性 T 细胞的作用。
