Single-Cell Landscape of Peripheral Blood Mononuclear Cells in Patients With Graves Disease

CONTEXT: Graves disease (GD) is a thyroid-specific autoimmune disease and the most common cause of hyperthyroidism. Its pathogenesis is associated with the disruption of immune tolerance and autoantibody production. However, the mechanisms underlying immune abnormalities remain incompletely elucidated. OBJECTIVE: To investigate changes in the cellular composition and function of peripheral blood mononuclear cells (PBMCs) in GD patients at single-cell resolution. METHODS: We employed single-cell RNA sequencing (scRNA-seq) and analyzed 22 680 peripheral blood mononuclear cells (PBMCs) from 8 GD patients and 12 healthy controls. RESULTS: Our results unveiled the single-cell landscape of PBMCs in GD patients, revealing substantial heterogeneity and changes in the cellular composition and function of PBMCs. We observed an increase in the proportion of CD16+ natural killer (NK) cells and memory cells in T and B lymphocyte subsets. This increase was accompanied by significantly enhanced functions, including cell activation, immune/defense responses, and inflammatory reactions. Additionally, we detected changes in the activity of transcription factors in various cell types, which were linked to the regulation of genes critical for immune and inflammation responses. Furthermore, we found a reduction in communication between NK cells and other immune cells, including CD4+ T cells, monocytes, and B cells, mediated by killer cell immunoglobulin-like receptor (KIR)-like inhibitory receptors, suggesting their involvement in the pathogenesis of GD. CONCLUSION: Our study revealed characteristic alterations in the composition and function of immune cell subsets in the PBMCs of GD patients. These findings shed light on the mechanisms underlying immune dysregulation in GD.