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

Kwok, A. J.; Soleimani, B.; Sun, B.; Fower, A.; Makuch, M.; Johnson, T.; Knight, J. C.; Ko, H.; Lennox, B.; Irani, S. R.; Handunnetthi, L.

2024-09-03 neurology
10.1101/2024.09.01.24311959 medRxiv
Show abstract

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.

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