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评估 GluN1-GluN2 异聚体活细胞检测法与 GluN1 单体生物芯片试剂盒检测法在抗 NMDAR 自身抗体检测中的一致性。

Evaluation of the concordance between GluN1-GluN2 heteromer live-cell-based assay and GluN1 monomer biochip kit assay on anti-NMDAR autoantibody detection.

机构信息

Department of Life Science, Medical Research Institute, Kanazawa Medical University, Kanazawa, Japan; Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata, Japan; Department of Multiple Sclerosis Therapeutics, Fukushima Medical University, School of Medicine, Fukushima, Japan.

Department of Life Science, Medical Research Institute, Kanazawa Medical University, Kanazawa, Japan.

出版信息

J Immunol Methods. 2021 Dec;499:113150. doi: 10.1016/j.jim.2021.113150. Epub 2021 Sep 22.

DOI:10.1016/j.jim.2021.113150
PMID:34560071
Abstract

Anti-N-methyl-d-aspartate receptor (NMDAR) antibodies are most frequently detected in autoantibody-related autoimmune encephalitis. Anti-NMDAR encephalitis mainly affects young women with ovarian teratoma, including acute to subacute onset of psychosis, seizures, consciousness disturbance, dyskinetic involuntary movements, autonomic dysfunction, and others. Diagnosis is based on the detection of anti-NMDAR autoantibodies in cerebrospinal fluid (CSF). The autoantibody recognizes the conformational epitope of the NMDA receptor. NMDA receptors contain hetero-tetramers of GluN1 (NR1) and GluN2/3 (NR2/3), in which GluN1 is essential to form functional receptors on the synaptic membrane in the brain. Thus, the autoantibodies are detected using neurons or culture cells expressing conformational receptors on their cell membrane, the natural form in the brain. The antibodies detected using artificial GluN1 monosubunit expressing cells as the antigens have been widely used for anti-NMDAR-antibody test. In the present study two detection systems were compared, a live-cell-based assay using human embryonic kidney (HEK) 293 cells expressing both of GluN1 and GluN2B, and a commercially available GluN1-monotransfected HEK cell biochip system. As the result, both the methods were equivalent, and the clinical features of both groups were similar, suggesting both tests have equal clinical significance.

摘要

抗 N-甲基-D-天冬氨酸受体 (NMDAR) 抗体最常存在于自身抗体相关的自身免疫性脑炎中。抗 NMDAR 脑炎主要影响伴有卵巢畸胎瘤的年轻女性,包括急性至亚急性发作的精神病、癫痫发作、意识障碍、不自主运动障碍、自主神经功能障碍等。诊断基于脑脊液 (CSF) 中抗 NMDAR 自身抗体的检测。该自身抗体识别 NMDA 受体的构象表位。NMDA 受体包含 GluN1 (NR1) 和 GluN2/3 (NR2/3) 的异四聚体,其中 GluN1 对于在大脑中的突触膜上形成功能性受体是必需的。因此,使用在细胞膜上表达构象受体的神经元或培养细胞来检测自身抗体,这是大脑中的自然形式。使用人工表达 GluN1 单亚基的细胞作为抗原检测到的抗体已被广泛用于抗 NMDAR 抗体检测。在本研究中比较了两种检测系统,一种是使用表达 GluN1 和 GluN2B 的人胚肾 (HEK) 293 细胞的基于活细胞的测定,另一种是市售的 GluN1 单转染 HEK 细胞生物芯片系统。结果两种方法等效,两组的临床特征相似,表明两种检测具有同等的临床意义。

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引用本文的文献

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NMDAR autoantibodies in psychiatric disease - An immunopsychiatric continuum and potential predisposition for disease pathogenesis.精神疾病中的N-甲基-D-天冬氨酸受体自身抗体——一种免疫精神病学连续体及疾病发病机制的潜在易感性
J Transl Autoimmun. 2022 Sep 21;5:100165. doi: 10.1016/j.jtauto.2022.100165. eCollection 2022.