Thymic Germinal Centers and Corticosteroids in Myasthenia Gravis: an Immunopathological Study in 1035 Cases and a Critical Review

Frédérique Truffault (1, 2) , Vincent de Montpreville (3) , Bruno Eymard (4) , Tarek Sharshar (5, 6) , Rozen Le Panse (2, 1) , Sonia Berrih-Aknin (1, 2)

1 Centre de recherche en myologie
2 Institut de Myologie
3 Service de pathologie [Hôptital Marie Lannelongue]
4 CHU Pitié-Salpêtrière [AP-HP]
5 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
6 Service médical des soins intensifs [CHU Raymond Poincaré]

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.

Mots clés: Autoimmune diseases; Chronic inflammation; Transcriptome; Thymic epithelial cells; Thymus; Genetic associations

Domaines: Immunologie

Frédérique Truffault, Vincent de Montpreville, Bruno Eymard, Tarek Sharshar, Rozen Le Panse, et al.. Thymic Germinal Centers and Corticosteroids in Myasthenia Gravis: an Immunopathological Study in 1035 Cases and a Critical Review. Clinical Reviews in Allergy and Immunology, 2016, pp.1-17. ⟨10.1007/s12016-016-8558-3⟩. ⟨hal-01338400⟩