脑脊液
免疫学
体细胞突变
自身免疫
NMDA受体
自身免疫性脑炎
免疫系统
医学
抗体
受体
生物
B细胞
病理
自身抗体
内科学
作者
Nancy Monson,Chad Smith,Herbert Greenberg,Patricia Plumb,Alyssa A. Guzman,Kam S. Tse,Chen Ding,Wei Zhang,Meleri Morgan,Haley E. Speed,Craig M. Powell,Sushobhna Batra,Lindsay G. Cowell,Scott Christley,Steven Vernino,Kyle Blackburn,Benjamin Greenberg
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2023-09-15
卷期号:211 (9): 1332-1339
标识
DOI:10.4049/jimmunol.2300156
摘要
Abstract Pediatric and adult autoimmune encephalitis (AE) are often associated with Abs to the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor (NMDAR). Very little is known regarding the cerebrospinal fluid humoral immune profile and Ab genetics associated with pediatric anti–NMDAR-AE. Using a combination of cellular, molecular, and immunogenetics tools, we collected cerebrospinal fluid from pediatric subjects and generated 1) flow cytometry data to calculate the frequency of B cell subtypes in the cerebrospinal fluid of pediatric subjects with anti–NMDAR-AE and controls, 2) a panel of recombinant human Abs from a pediatric case of anti–NMDAR-AE that was refractory to treatment, and 3) a detailed analysis of the Ab genes that bound the NR1 subunit of the NMDAR. Ag-experienced B cells including memory cells, plasmablasts, and Ab-secreting cells were expanded in the pediatric anti–NMDAR-AE cohort, but not in the controls. These Ag-experienced B cells in the cerebrospinal fluid of a pediatric case of NMDAR-AE that was refractory to treatment had expanded use of variable H chain family 2 (VH2) genes with high somatic hypermutation that all bound to the NR1 subunit of the NMDAR. A CDR3 motif was identified in this refractory case that likely drove early stage activation and expansion of naive B cells to Ab-secreting cells, facilitating autoimmunity associated with pediatric anti–NMDAR-AE through the production of Abs that bind NR1. These features of humoral immune responses in the cerebrospinal fluid of pediatric anti–NMDAR-AE patients may be relevant for clinical diagnosis and treatment.
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