Publications

Anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) is a prevalent autoimmune neurological disorder, yet T cell-driven immunopathology and its contributions to therapeutic resistance and fulminant neuroinflammation remain poorly defined. Integrative single-cell multi-omic profiling, combining single-cell RNA sequencing, single-cell T cell receptor (TCR) sequencing, and cellular indexing of transcriptomes and epitopes by sequencing, is applied to systematically map peripheral and cerebrospinal fluid (CSF) immune landscapes in treatment-na & iuml;ve NMDAR-E patients, with orthogonal validation conducted across independent cohorts via multiparameter flow cytometry and ex vivo NR1 peptide stimulation. Clonally expanded CX3CR1-expressing CD4+ and CD8+ T cells are identified as a core disease-associated effector population, characterized by high predicted affinity for the pathogenic GluN1 N368/G369 epitope, robust proinflammatory and cytotoxic transcriptional programs, and enhanced intercellular crosstalk with activated B cells through major histocompatibility complex (MHC), CD99, and macrophage migration inhibitory factor signaling axes. Preferentially enriched in patient CSF, these cells produce elevated interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) upon antigen-specific stimulation, collectively highlighting a disease-associated inflammatory T cell state linked to peripheral immune activation and CNS immune remodeling, with potential translational relevance for future biomarker and therapeutic investigation.

JTD Keywords: Anti-nmda receptor encephalitis, Brain, Cx3cr1, Expression, Neuroinflammation, Single-cell multi-omics, T cell receptor clonality, T cells, T-cells