Study of B Cell Repertoire in Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

Jingjing Feng,Yinwei Sun,Zhidong Zhang,Liying Cui,Hongzhi Guan,Haitao Ren,Xiaotun Ren,Weihua Zhang,Jing Wang,Siyuan Fan,Wenhan Li,Bin Peng

doi:10.3389/fimmu.2020.01539

Abstract

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common antibody-mediated encephalitis. There are several studies on B cell repertoire of anti-NMDAR encephalitis in Caucasians. Here, the cerebrospinal fluid (CSF) samples of 12 Chinese patients with first-episode anti-NMDAR encephalitis were collected to investigate the B cell receptor (BCR) binding to NMDAR by single cell amplification of BCR and Sanger sequencing. BCR data of healthy persons, and of patients with anti-leucine-rich glioma inactivated 1 (anti-LGI1) encephalitis, multiple sclerosis (MS), and neuromyelitis optica spectrum disorder (NMOSD) from the public databases were used as control. A heavy chain common clone IGHV1-18*04,IGHD1-26*01/ IGHD2-2*03/IGHD2-8*01, IGHJ3*02_(CDR3) ARVGSKYGFETFDI was found in 11 of 12 enrolled patients but not in the comparison data set. In addition, 4 shared clonotypes were found among these patients, and three of them contained the common clone. This study also revealed that the antibody gene family usage preference between patients and healthy controls were different, while they had similar antibody mutation rate. Our findings may have potential clinical implications for the diagnosis of anti-NMDAR encephalitis.

Highlights

Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a severe multistage neuropsychiatric syndrome and is associated with cerebrospinal fluid (CSF) IgG antibodies against the NR1 subunit of the N-methyl-D-aspartate receptor (NMDAR)
We found that 0.4–1.9% of CSF cells could bind to the NR1 fluorescent antigen, and 0.1–1.4% of B cells in CSF could bind to the NR1 subunit (Figure 1), which was consistent with the result previously reported [16]
The major findings of our research include: first, a heavy chain common clone of B cell receptor appeared in 11 of 12 patients, but not in healthy people or patients with anti-LGI1 encephalitis, multiple sclerosis (MS), or neuromyelitis optica spectrum disorder (NMOSD); second, four shared clonotypes presented among different patients with anti-NMDAR encephalitis; third, the V

Summary

Introduction

Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a severe multistage neuropsychiatric syndrome and is associated with cerebrospinal fluid (CSF) IgG antibodies against the NR1 subunit of the NMDAR. In 2007, the target antigens were identified to be the NMDARs by Dalmau et al [1]. Numerous patients with anti-NMDAR encephalitis were identified. AntiNMDAR encephalitis is the most common form of antibody-mediated encephalitis and occurs more frequently than any individual viral cause of encephalitis in young persons [2]. In China, it is reported that about 12.9% of unexplained encephalitis cases are autoimmune encephalitis (AE), of which anti-NMDAR encephalitis accounts for 80% [3].

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Conclusion