Comprehensive B-Cell Immune Repertoire Analysis of Anti-NMDAR Encephalitis and Anti-LGI1 Encephalitis.

Jingjing Feng,Hongzhi Guan,Siyuan Fan,Yinwei Sun,Haitao Ren,Jing Wang

doi:10.3389/fimmu.2021.717598

Abstract

Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) and anti-leucine-rich glioma-inactivated 1 encephalitis (anti-LGI1E) are the two most common types of antibody-mediated autoimmune encephalitis. We performed a comprehensive analysis of the B-cell immune repertoire in patients with anti-NMDARE (n = 7) and anti-LGI1E (n = 10) and healthy controls (n = 4). The results revealed the presence of many common clones between patients with these two types of autoimmune encephalitis, which were mostly class-switched. Additionally, many differences were found among the anti-NMDARE, anti-LGI1E, and healthy control groups, including the diversity of the B-cell immune repertoire and gene usage preference. These findings suggest that the same adaptive immune responses occur in patients with anti-NMDARE and anti-LGI1E, which deserves further exploration.

Highlights

Anti-N-methyl-D-aspartate receptor encephalitis is mediated by antibodies against NMDA receptors
Analysis of the characteristics of IGHV and IGHJ gene usage preference (Figure 2A and Supplementary Table 3) showed that patients with anti-NMDARE had significant differences compared with healthy controls (HC), including increased IGHJ4 (Padj = 0.028) and decreased IGHV3-71 (Padj = 0.036) levels; patients with anti-NMDARE had significant differences compared with patients with anti-LGI1E, including increased IGHV1-67 (Padj = 0.043) and IGHV4-4 (Padj = 0.006) levels
We characterized the role of B cells in patients with antiNMDARE and anti-LGI1E and HC at the B-cell receptor (BCR) level

Summary

Introduction

Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is mediated by antibodies against NMDA receptors. The main binding site of anti-NMDAR IgG is the N368/G369 amino acids at the N-terminal of the NR1 subunit of NMDA receptors [1,2,3]. The main classes of pathogenic antibodies in anti-NMDARE are IgG1 and IgG3, which are synthesized intrathecally [4]. The positive rate of anti-NMDAR IgG in the cerebrospinal fluid of patients is nearly 100% [4], but this rate is only 71.4%–85.6% in serum samples [5, 6]. Previous studies have revealed that anti-NMDAR antibodies can alter the normal interaction between NMDA receptors and EphB2, displacing these receptors from synaptic to

Methods

Results

Conclusion