Thymic Germinal Centers and Corticosteroids in Myasthenia Gravis: an Immunopathological Study in 1035 Cases and a Critical Review.
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.
INSERM U974, Paris, France.|CNRS FRE3617, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Paris, France.|AIM, Institut de myologie, Paris, France.
Frédérique
F
Truffault
Department of Pathology, Marie Lannelongue Hospital, Le Plessis Robinson, 92350, France.
Vincent
V
de Montpreville
Department of Neuromuscular Disorders, CHU Salpêtrière, Paris, France.
Bruno
B
Eymard
General Intensive Care Medicine, Assistance Publique Hôpitaux de Paris, Raymond Poincaré Hospital, University of Versailles Saint-Quentin en Yvelines, 92380, Garches, France.
Tarek
T
Sharshar
INSERM U974, Paris, France.|CNRS FRE3617, Paris, France.|Sorbonne Universités, UPMC Univ Paris 06, Paris, France.|AIM, Institut de myologie, Paris, France.
Rozen
R
Le Panse
INSERM U974, Paris, France. sonia.berrih-aknin@upmc.fr.|CNRS FRE3617, Paris, France. sonia.berrih-aknin@upmc.fr.|Sorbonne Universités, UPMC Univ Paris 06, Paris, France. sonia.berrih-aknin@upmc.fr.|AIM, Institut de myologie, Paris, France. sonia.berrih-aknin@upmc.fr.|UMRS 974 UPMC, INSERM, FRE 3617 CNRS, AIM, Center of Research in Myology, 105 Boulevard de l'Hôpital, Paris, 75013, France. sonia.berrih-aknin@upmc.fr.
Sonia
S
Berrih-Aknin
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D018858:Germinal Center / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000473:pathology*
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents
Autoimmune diseases; Chronic inflammation; Genetic associations; Thymic epithelial cells; Thymus; Transcriptome