Lu sur http://onlinelibrary.wiley.com/wol1/doi ... 9/abstract
Traduction disponible directement en cliquant en bas à droite de ce message sur notre forum
Role of the thymus in autoimmune myasthenia gravis
Version of Record online: 31 JUL 2016
Thymic pathologies are frequently associated with myasthenia gravis. Although thymoma is found in both men and women mostly after the age of 40 years, thymic follicular hyperplasia is very common in young women.
Thymomas are associated with high autoreactivity and reduced efficiency of tolerance mechanisms, at least partially due to the absence of functional medullary epithelial cells.
In follicular hyperplasia, the presence of ectopic germinal centers is evocative of what is described in other autoimmune disorders, where germinal centers are found in the inflamed tissues. The grade of follicular hyperplasia is correlated with the serum level of anti-acetylcholine receptor (AChR) antibody, suggesting that the thymic hyperplasia contributes to the production of anti-AChR antibodies. Cellular and molecular analysis of thymic follicular hyperplasia shows changes in the Th1/Th17/regulatory T cell balance, with increased expression of Th1 and Th17 cytokines, and defective function of regulatory T cells.
Follicular hyperplasia is also characterized by active neo-angiogenesis, and increased chemokine synthesis, namely CXCL13 and CCL21, which play a major role in the generation of germinal centers. This inflammatory environment recruits peripheral B cells, and together with the overexpression of the autoantigen could specifically lead to the anti-AChR autoimmune response. The individual predisposing background includes gene polymorphism, but also hormones, vitamin D level and other environmental components.
Overall, the functional and morphological changes observed in the thymus, the improvement of patients after thymectomy, and the correlation between the degree of follicular hyperplasia and the level of anti-AChR antibodies suggest a causal relationship between thymic pathology and MG.