Jingqun Tang, Ziming Ye, Yi Liu, Mengxiao Zhou, Chao Qin*
Purpose: Defective stem cells have been recognized as being associated with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, autoimmune cytopenias and Myasthenia Gravis (MG). However, the differential gene expression profile of Bone Marrow Mononuclear Cells (BMMCs) and the molecular mechanisms underlying MG pathogenesis have not been fully elucidated. Therefore, we investigated the abnormal expression and potential roles and mechanisms of mRNAs in BMMCs among patients with MG with or without thymoma.
Methods: Transcription profiling of BMMCs in patients with MG without thymoma (M2) and patients with thymoma-associated MG (M1) was undertaken by using high-throughput RNA sequencing (RNA-Seq), and diseaserelated differentially expressed genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR).
Results: RNA-Seq demonstrated 60 significantly upregulated and 65 significantly downregulated genes in M2 compared with M1. Five disease-related differentially expressed genes were identified and validated by qRT-PCR analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to predict the functions of aberrantly expressed genes. Recombination activating 1 (RAG1), RAG2, BCL2-like 11, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform and repressor element- 1-silencing transcription factor might play roles in MG pathogenesis involving the primary immunodeficiency signaling pathway, signaling pathways regulating pluripotency of stem cells and fork head box O signaling pathway.
Conclusion: The aberrantly expressed genes of BMMCs in M1 or M2 patients demonstrate the underlying mechanisms governing the pathogenesis of MG.