Thymoma and paraneoplastic myasthenia gravis

• Published in: Autoimmunity (Chur, Switzerland) Vol. 43; no. 5-6; pp. 413 - 427
• Main Authors: Marx, A., Willcox, N., Leite, M. I., Chuang, W.-Y., Schalke, B., Nix, W., Ströbel, P.
• Format: Journal Article
• Language: English
• Published: England Informa 01.08.2010; Taylor & Francis
• Subjects: AIRE Protein; Autoantibodies - immunology; Autoantigens - immunology; Autoantigens - metabolism; Autoimmunity; Epithelial Cells - pathology; Genes, MHC Class II; Humans; Immunoglobulin G - immunology; Lymphopoiesis; myasthenia gravis; Myasthenia Gravis - genetics; Myasthenia Gravis - immunology; Myasthenia Gravis - physiopathology; Paraneoplastic Syndromes, Nervous System - genetics; Paraneoplastic Syndromes, Nervous System - immunology; Polyendocrinopathies, Autoimmune - immunology; T-Lymphocytes - immunology; thymoma; Thymoma - genetics; Thymoma - immunology; Thymoma - pathology; Thymoma - physiopathology; Thymus Gland - physiopathology; Transcription Factors - genetics
• ISSN: 0891-6934; 1607-842X
• DOI: 10.3109/08916930903555935

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.