Single-cell RNA-seq of myasthenia gravis reveals transcriptional heterogenity and dysfunction of immune cell populations

The immune system imbalance and immune cell dysfunction of myasthenia gravis (MG) have been thoroughly studied, but the composition and function of immune cell subsets at single cell level in thymus and peripheral blood remain unclear. Here, we performed single-cell RNA sequencing with 9701 and 23846 cells respectively originated from the peripheral blood and thymus samples of MG patients, and 6 930 cells from the peripheral blood of healthy controls, and identified 4 major cell populations of T cells, B cells, myeloid cells, and NK cells, as well as their 15 cell subpopulations. We found an absolute predominance of T cells in the thymus and peripheral blood of MG patients, and the proportions of memory B cells in both plasma and thymus are significantly increased while the number of naïve B cells is significantly reduced in MG patients compared to healthy controls. Besides, the plasma cells in the peripheral blood of MG patients had the strongest interactions with other cells, while monocytes in the thymic tissue had the strongest interactions with other cells. On the whole, our research clarify the cellular heterogeneity in the pathogenesis of MG, and characterize the immune microenvironment of thymic tissues in MG patients.