title: Thymoma and paraneoplastic myasthenia gravis.
abstract: Paraneoplastic autoimmune diseases associate occasionally with small cell lung cancers and gynecologic tumors. However, myasthenia gravis (MG) occurs in at least 30% of all patients with thymomas (usually present at MG diagnosis). These epithelial neoplasms almost always have numerous admixed maturing polyclonal T cells (thymocytes). This thymopoiesis-and export of mature CD4(+)T cells-particularly associates with MG, though there are rare/puzzling exceptions in apparently pure epithelial WHO type A thymomas. Other features potentially leading to inefficient self-tolerance induction include defective epithelial expression of the autoimmune regulator (AIRE) gene and/or of major histocompatibility complex class II molecules in thymomas, absence of myoid cells, failure to generate FOXP3(+) regulatory T cells, and genetic polymorphisms affecting T-cell signaling. However, the strong focus on MG/neuromuscular targets remains unexplained and suggests some biased autoantigen expression, T-cell selection, or autoimmunization within thymomas. There must be further clues in the intriguing serological and cellular parallels in some patients with late-onset MG but without thymomas-and in others with AIRE mutations-and in the contrasts with early-onset MG, as discussed here.
authors.affiliation: Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, D-68135 Mannheim, Germany. alexander.marx@umm.de
authors.forename: A
authors.initials: A
authors.lastname: Marx
authors.forename: N
authors.initials: N
authors.lastname: Willcox
authors.forename: M I
authors.initials: MI
authors.lastname: Leite
authors.forename: W-Y
authors.initials: WY
authors.lastname: Chuang
authors.forename: B
authors.initials: B
authors.lastname: Schalke
authors.forename: W
authors.initials: W
authors.lastname: Nix
authors.forename: P
authors.initials: P
authors.lastname: Ströbel
mesh_terms: D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology; D005802:Genes, MHC Class II; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D038041:Lymphopoiesis; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D020361:Paraneoplastic Syndromes, Nervous System / Q000235:genetics / Q000276:immunology*; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013945:Thymoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D013950:Thymus Gland / Q000503:physiopathology*; D014157:Transcription Factors / Q000235:genetics; D000096927:AIRE Protein
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D014157:Transcription Factors; D000096927:AIRE Protein