Thymoma and paraneoplastic myasthenia gravis.
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.
Marx
A
A
Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, D-68135 Mannheim, Germany. alexander.marx@umm.de
Willcox
N
N
Leite
M I
MI
Chuang
W-Y
WY
Schalke
B
B
Nix
W
W
Ströbel
P
P
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
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D014157:Transcription Factors; D000096927:AIRE Protein