Single-cell immune survey identifies a novel pathogenic role for T cells in anti-NMDA receptor encephalitis

We performed single-cell RNA and immune receptor repertoire sequencing of an N-methyl-D-aspartate receptor encephalitis (NMDARE) patient in relapse and remission states, as well as an autoimmune psychosis (AP) patient with anti-NMDAR antibodies. We leveraged publicly available cerebrospinal fluid (CSF) single-cell sequencing data from other neurological disorders to contextualise our findings. Results highlight a key role for T-cells in NMDARE pathogenesis with clonal expansion of both cytotoxic CD4+ and CD8+ effector memory cells in CSF. We further identified interferon responsive B-cells in the CSF during the acute phase of NMDARE and a higher proportion of mononuclear phagocytes in the CSF of AP. Collectively, our work sheds light into the immunobiology of anti-NMDAR antibody-mediated disease.