Single-cell RNA-sequencing of myasthenia gravis reveals transcriptional heterogeneity and dysfunction of immune cell populations

The purpose of this study was to explore the composition and function of immune cell subsets at the single cell level in thymus and peripheral blood of patients with myasthenia gravis (MG). A total of 9701 and 23846 cells respectively originated from the peripheral blood and thymus samples of 2 MG patients, and 6930 cells from the peripheral blood of 2 gender- and aged-matched healthy controls were selected for single-cell RNA sequencing. UMAP, GO, KEGG pathway analysis, Monocle3 and Velcyto were performed to analyze the composition, molecular and functional properties, and developmental trajectory of immune cell subsets. Four major cell populations of T cells, B cells, myeloid cells, and NK cells were identified, as well as their 15 cell subpopulations. An absolute predominance of T cells was found in the thymus and peripheral blood of MG patients, and the proportions of memory B cells in both plasma and thymus showed an increasing trend while the number of naïve B cells demonstrated a decreasing trend in MG patients compared with healthy controls. Besides, the monocytes in the peripheral blood of MG patients had the strongest interactions with other cells. Furthermore, CXCL, GAS, and CD30 signaling pathways were more enriched within MG peripheral blood. Our research clarifies the cellular heterogeneity in the pathogenesis of MG and characterizes the immune microenvironment of thymic tissues in MG patients.