Postdoctoral Associate Duke University Durham, North Carolina, United States
Abstract Text:
Objective: To characterize the immunological signatures of thymus in patients with AChR-MG.
Methods: We collected matched thymus samples and peripheral blood monocytes (PBMCs) from two patients diagnosed with early-onset AchR-MG. To identify and characterize immune cell subsets within the thymus and PBMCs, we applied high-resolution single-cell RNA sequencing (scRNA-seq) technology. After removing the dead cells and following sequencing, we performed bioinformatic analysis. Public available dataset of age and sex-matched healthy controls (HC) were also included.
Results: A total of 39,943 single cells derived from thymocytes and PBMCs passed QC. Twenty-four immune cell clusters were identified. Comparing thymocytes, we observed a significant decrease in double positive T cells, along with an increase in CD4 T cells, B cells, NK and DCs in MG patients than HC. In PBMCs, we observed a significant increase in double positive T cells and CD4 T cells, while NK cells, DCs and monocytes were decreased in MG patients. Overall, our findings indicate a shift of double positive T cells from thymus to periphery, and an increase of B cells, NK cells and DCs in the thymus of MG patients.
SUMMARY/
Conclusion: Our study highlights the presence of an immune cell imbalance between the thymus and peripheral circulation in MG patients. Further investigations are necessary to confirm the underlying mechanisms and elucidate the role of these imbalanced immune cells in the pathogenesis of MG.