Pathogenesis of thymoma-associated myasthenia gravis: a narrative review

Patients with thymomas often develop autoimmune neuromuscular diseases, including myasthenia gravis (MG). Autoantigen expression in thymomas plays an important role in disease pathogenesis. Since thymomas are mainly composed of the cortex, with few medullae, MG may be caused by immature thymoma-derived T cells that fail to undergo negative selection and have not yet acquired sufficient self-tolerance. However, due to the complexity and diversity of thymoma cell populations, a comprehensive understanding of the mechanisms underlying its association with MG has yet to be achieved. The purpose of this article is to provide an overview of the normal thymus function and the pathogenesis of thymoma associated with MG and other autoimmune diseases, with the aim to highlight newly identified mechanisms that may offer novel insights into their development.

To address the lack of information regarding the MG-thymoma association, we applied a bioinformatics approach to thymomas.

By analyzing bulk RNA-sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) data from thymomas, we identified neuromuscular medullary thymic epithelial cells (nmTECs) as neuromuscular antigen-expressing cell populations. Medullary structures, although much smaller than those of the normal thymus, are present in thymomas with MG and MG-susceptible genes are clustered. We observed spatial nmTEC colocalization and an immune niche, inferring an interaction and suggesting a pathological role of nmTECs in MG.

After providing an up-to-date overview of normal thymus function, along with data and hypotheses regarding the association between thymoma and MG, we present bioinformatic findings regarding the thymoma.