Characterizing immune cell dynamics in anti-NMDAR encephalitis via single-cell transcriptomics 9363

Abstract Description Introduction Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR-E) is a complex autoimmune disease, and the precise molecular and immunological events leading to the generation of anti-NMDAR autoantibodies remain unclear. Material/method: Herein, We utilized single-cell RNA sequencing (scRNA-seq) to characterize peripheral blood mononuclear cells (PBMCs) from patients with anti-NMDAR encephalitis (n = 3) and healthy controls (n = 3), analyzing a total of 36,000 cells. Clustering and annotation were conducted using Seurat and SingleR 2.8.0. Results There was no significant difference in the frequency of the 29 major cell groups among the cases. Anti-NMDAR-E patients exhibited upregulation of differential expression genes (DEGs) associated with immune regulation of inflammatory response and migration (CCL3, RORA, IL1B, CCL4, AIM2 in B cells, CD160, LAIR2, EOMES, CXCR6 in T cells). KEGG pathway analysis also highlighted upregulation of cytokine-cytokine receptor interaction and Th1-Th17 cell differentiation pathways in T cells; Toll-like receptor signaling and NF-kappa B signaling pathways in B cells. Discussion: Our findings suggest that immune dysregulation in anti-NMDAR encephalitis involves key genes and pathways in B and T cells. These results highlight the potential role of immune modulation in developing targeted treatments for the disease. Funding Sources Supported by Istanbul University-BAP TDK-2024-40786; Istanbul University-BAP TOA-2021-37862, TUBITAK-2214/A-International Research Fellowship Programme For PhD Students (1059B142100522). Topic Categories Neuroimmunology (NEUR)