title: The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes.
abstract: The thymus plays distinct roles in the pathogenesis of the different Myasthenia gravis (MG) subtypes. Inflammatory, neoplastic and age-related alterations of the thymus are of pivotal relevance for the initiation of anti-acetylcholine receptor (AChR) autoimmunity in early onset MG, thymoma-associated MG and, likely, late onset MG, respectively. By contrast, the thymus is presumably not related to MG that is due to autoantibodies to the muscle specific kinase, MuSK. Finally, the role of the thymus is still obscure in MG defined by antibodies against the agrin receptor LRP4 and in MG without all of the above autoantibdies (triple sero-negative MG) since these MG subtypes have been described only recently and thymectomy has not been their standard treatment. This review aims to give an update on intrathymic mechanisms of tolerance breakdown in MG, including abnormal T cell selection and activation, the role of thymic myoid cells, the autoimmune regulator (AIRE) and regulatory T cells.
authors.affiliation: Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. alexander.marx@umm.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Marx
authors.forename: Frederick
authors.initials: F
authors.lastname: Pfister
authors.forename: Berthold
authors.initials: B
authors.lastname: Schalke
authors.forename: Güher
authors.initials: G
authors.lastname: Saruhan-Direskeneli
authors.forename: Arthur
authors.initials: A
authors.lastname: Melms
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D006801:Humans; D009157:Myasthenia Gravis / Q000145:classification / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology* / Q000503:physiopathology*
chemical_list: D001323:Autoantibodies; D011950:Receptors, Cholinergic; D020794:Receptor Protein-Tyrosine Kinases