Development and measurement of anti-NMDA receptor antibody assay in blood to elucidate the etiology of psychiatric disorders

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K08087
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Osaka General Medical Center
• Principal Investigator: Matsunaga Hidenori 地方独立行政法人大阪府立病院機構大阪急性期・総合医療センター(臨床研究支援センター), 精神科, 医師 (70603843)
• Co-Investigator(Kenkyū-buntansha): 福森 亮雄 大阪医科薬科大学, 薬学部, 教授 (00788185) ; 多田 敬典 至学館大学, 健康科学部, 教授 (20464993) ; 田中 惠子 新潟大学, 脳研究所, 非常勤講師 (30217020)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 抗NMDA受容体抗体 / ウサギ網赤血球由来蛋白合成システム / コムギ胚芽由来蛋白合成システム / ラジオリガンドアッセイ / 膜蛋白 / cell based assay / 自己免疫性脳炎 / 精神疾患

Outline of Final Research Achievements

We aimed to develop an assay system that can simultaneously measure multiple samples as an alternative to the cell-based assay currently used to detect anti-NMDA receptor antibodies. We synthesized the receptor protein using a protein synthesis system derived from rabbit reticulocyte lysate and membrane components, but were unable to detect autoantibodies. Next, receptor protein synthesis was performed using a wheat germ-derived protein synthesis system with multiple types of synthetic reaction solutions, but without success. Furthermore, an attempt was made to synthesize the extracellular portion (ATD) of NR1 subunit of NMDA receptor containing the epitope of the autoantibody in a rabbit reticulocyte system, but detection of autoantibodies was difficult. On the other hand, in a cell-based assay system using cultured cells in which the NR1 subunit of the NMDA receptor was expressed on the cell surface, anti-NMDA receptor antibodies in the spinal fluid of the patients were detected.

Free Research Field

精神神経医学

Academic Significance and Societal Importance of the Research Achievements

NMDA受容体を細胞表面に発現させた培養細胞を用いる現行のcell-based assayに代わる、多検体を同時に測定できる抗NMDA受容体抗体測定系の開発を目指したが、無細胞蛋白合成系を用いて作成した受容体蛋白では、抗NMDA受容体抗体を検出することはできなかった。このことから、病原性のある抗NMDA受容体抗体の検出には受容体本来の立体構造が不可欠であり、現時点では、現行のcell based assayが妥当な測定法であることが確認された。