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抗 N-甲基-D-天冬氨酸受体脑炎患者 B 细胞受体谱研究。

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

机构信息

CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China.

Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.

出版信息

Front Immunol. 2020 Jul 29;11:1539. doi: 10.3389/fimmu.2020.01539. eCollection 2020.

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 IGHV1-1804,IGHD1-2601/ IGHD2-203/IGHD2-801, IGHJ302_(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.

摘要

抗 N-甲基-D-天冬氨酸受体(NMDAR)脑炎是最常见的抗体介导性脑炎。已有几项关于白种人抗 NMDAR 脑炎 B 细胞库的研究。本研究通过单细胞扩增 B 细胞受体(BCR)和 Sanger 测序,检测了 12 例首发抗 NMDAR 脑炎患者的脑脊液(CSF)样本中 BCR 与 NMDAR 的结合情况。以公共数据库中的健康对照者、抗亮氨酸丰富胶质瘤失活 1 (anti-LGI1)脑炎、多发性硬化症(MS)和视神经脊髓炎谱系障碍(NMOSD)患者的 BCR 数据作为对照。在 12 例入组患者中,发现 11 例存在 IGHV1-1804、IGHD1-2601/IGHD2-203/IGHD2-801、IGHJ302_(CDR3)ARVGSKYGFETFDI 重链常见克隆,但在对照组中未发现。此外,在这些患者中发现了 4 个共享的克隆型,其中 3 个包含常见克隆。本研究还表明,患者和健康对照组的抗体基因家族使用偏好不同,而它们的抗体突变率相似。我们的研究结果可能对抗 NMDAR 脑炎的诊断具有潜在的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dcd/7403192/68313e41e365/fimmu-11-01539-g0001.jpg

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