The most common form of
Myasthenia gravis (MG) is due to anti-
acetylcholine receptor (AChR)
antibodies and is frequently associated with thymic pathology. In this review, we discuss the immunopathological characteristics and molecular mechanisms of thymic follicular
hyperplasia, the effects of
corticosteroids on this thymic pathology, and the role of thymic epithelial cells (TEC), a key player in the inflammatory thymic mechanisms. This review is based not only on the literature data but also on thymic transcriptome results and analyses of pathological and immunological correlations in a vast cohort of 1035 MG patients without
thymoma. We show that among patients presenting a
thymic hyperplasia with germinal centers (GC), 80 % are females, indicating that thymic follicular
hyperplasia is mainly a disease of women. The presence of anti-AChR
antibodies is correlated with the degree of follicular
hyperplasia, suggesting that the thymus is a source of anti-AChR
antibodies. The degree of
hyperplasia is not dependent upon the time from the onset, implying that either the
antigen is chronically expressed and/or that the mechanisms of the resolution of the GC are not efficiently controlled.
Glucocorticoids, a conventional
therapy in MG, induce a significant reduction in the GC number, together with changes in the expression of
chemokines and angiogenesis. These changes are likely related to the acetylation molecular process, overrepresented in
corticosteroid-treated patients, and essential for gene regulation. Altogether, based on the pathological and molecular thymic abnormalities found in MG patients, this review provides some explanations for the benefit of
thymectomy in early-onset MG patients.