Single-cell RNA sequencing reveals diverse B cell phenotypes in patients with anti-NMDAR encephalitis.
Psychiatry Clin Neurosci
; 78(3): 197-208, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38063052
ABSTRACT
BACKGROUNDS Anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) is a severe autoimmune disorder characterized by prominent psychiatric symptoms. Although the role of NMDAR antibodies in the disease has been extensively studied, the phenotype of B cell subsets is still not fully understood. METHODS:
We utilized single-cell RNA sequencing, single-cell B cell receptor sequencing (scBCR-seq), bulk BCR sequencing, flow cytometry, and enzyme-linked immunosorbent assay to analyze samples from both NMDAR-E patients and control individuals.RESULTS:
The cerebrospinal fluid (CSF) of NMDAR-E patients showed significantly increased B cell counts, predominantly memory B (Bm) cells. CSF Bm cells in NMDAR-E patients exhibited upregulated expression of differential expression genes (DEGs) associated with immune regulatory function (TNFRSF13B and ITGB1), whereas peripheral B cells upregulated DEGs related to antigen presentation. Additionally, NMDAR-E patients displayed higher levels of IgD- CD27- double negative (DN) cells and DN3 cells in peripheral blood (PB). In vitro, DN1 cell subsets from NMDAR-E patients differentiated into DN2 and DN3 cells, while CD27+ and/or IgD+ B cells (non-DN) differentiated into antibody-secreting cells (ASCs) and DN cells. NR1-IgG antibodies were found in B cell culture supernatants from patients. Differential expression of B cell IGHV genes in CSF and PB of NMDAR-E patients suggests potential antigen class switching.CONCLUSION:
B cell subpopulations in the CSF and PB of NMDAR-E patients exhibit distinct compositions and transcriptomic features. In vitro, non-DN cells from NMDAR-E can differentiate into DN cells and ASCs, potentially producing NR1-IgG antibodies. Further research is necessary to investigate the potential contribution of DN cell subpopulations to NR1-IgG antibody production.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encefalite Antirreceptor de N-Metil-D-Aspartato
Limite:
Humans
Idioma:
En
Revista:
Psychiatry Clin Neurosci
Assunto da revista:
NEUROLOGIA
/
PSIQUIATRIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China