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.

Keywords::

• Autoimmunity
• thymoma
• myasthenia gravis

Declaration of interest: This work was supported by European Union Grants LSHB-CT-2003-503410 (Euro-Thymaide) and No. 2005105 (EuroMyasthenia Network) and by Grant 106430 of the Deutsche Krebshilfe (A.M. and P.S.). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.