Autoreactive T cells and thymic atrophy pathway in thymic hyperplasia patients with myasthenia gravis

Background T cells play a vital role in antigen presentation, immune tolerance imbalance, and secretion of pathogenic cytokines in the progression of Myasthenia Gravis (MG). Previous studies have founded that patients with thymic hyperplasia accompanied by MG exhibit autoreactive T cells in thymus that can recognize self-antigens at the neuromuscular junction (NMJ), leading to the destruction of acetylcholine receptors (AChR) and the appearance of muscle weakness. Furthermore, Thymic hyperplasia is associated with T-cell-related autoimmune diseases, and increased expression of WNT4 and FOXN1 are beneficial to the growth of thymic cells and the maintenance of the thymic microenvironment. Methods The samples were obtained from surgical patients who met the criteria, and this study was ethically approved. We first measured the proportion of T cell subsets in the peripheral blood and thymus of thymic hyperplasia patients with and without myasthenia gravis. Then, we quantified the WNT4 and FOXN1 proteins in the thymus. Finally, we used the Pearson correlation test to analyze the correlation between autoreactive T cells and the thymic atrophy pathway. Results Flow cytometry clarified that Th1 and Th17 cells were elevated in the peripheral blood and thymus of patients with MG (1.207 ± 1.444 and 3.788 ± 0.6920 in Th1, 7.683 ± 1.025 and 0.3127 ± 0.1936 in Th17). Western blotting revealed increased expression of key molecules in the thymic atrophy pathway, WNT4 and FOXN1, in the MG group. Additionally, the abnormal activation of the thymic atrophy pathway may be one of the causes of autoreactive T cell production. Conclusion Our study has identified an increased number of Th1 and Th17 cells in the peripheral blood and thymus of patients with thymic hyperplasia associated MG. Quantitative analysis of proteins and RNA indicates that the expression of WNT4 and FOXN1 is upregulated in patients with thymic hyperplasia accompanied by MG. Additionally, the abnormal activation of the thymic atrophy pathway may be one of the causes of autoreactive T cell production. This research provides a potential perspective on the pathogenesis of MG in patients with thymic hyperplasia.