Thymic remodeling associated with hyperplasia in myasthenia gravis.
Acquired myasthenia gravis (MG), a neurological autoimmune disease, is caused by autoantibodies against components of the neuromuscular junction that lead to disabling muscle fatigability. The thymus is clearly involved in the pathogenesis of early-onset MG with anti-acetylcholine receptor antibodies, and thymic hyperplasia of lympho-proliferative origin is a hallmark of the disease. In this review, we describe the structural and cellular changes associated with thymic hyperplasia, its main characteristics being the development of ectopic germinal centers (GCs) associated with active neoangiogenic processes, such as development of high endothelial venules and lymphangiogenesis. What triggers such thymic abnormalities in MG is not yet clear. A thymic transcriptome analysis has demonstrated a strong inflammatory signature in MG that could orchestrate the development of thymic hyperplasia. In this context, thymic epithelial cells (TECs) seem to play a central role, either by contributing or responding to the inflammatory environment and up-regulating the autoimmune response. In particular, MG TECs clearly overexpress various cytokines, among which chemokines play a crucial role in the recruitment of peripheral lymphocytes to the thymus via the newly expanded vessel network, thereby leading to the development of ectopic GCs. Clearly, a better understanding of major events that lead to thymic hyperplasia will help optimize strategies toward more specific therapy for MG.
Le Panse
Rozen
R
Hôpital Marie Lannelongue, CNRS UMR 8162, 92350 Le Plessis-Robinson, France. rozen.lepanse@u-psud.fr
Bismuth
Jacky
J
Cizeron-Clairac
Géraldine
G
Weiss
Julia Miriam
JM
Cufi
Perrine
P
Dartevelle
Philippe
P
De Rosbo
Nicole Kerlero
NK
Berrih-Aknin
Sonia
S
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D018925:Chemokines / Q000502:physiology; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D006965:Hyperplasia; D007372:Interferons / Q000502:physiology; D042583:Lymphangiogenesis; D009157:Myasthenia Gravis / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D009469:Neuromuscular Junction / Q000276:immunology / Q000473:pathology; D011978:Receptors, Nicotinic / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology
D001323:Autoantibodies; D018925:Chemokines; D011978:Receptors, Nicotinic; D007372:Interferons