Clarify the pathological mechanism for autoimmune encephalitis using recombinant autoantibodies

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22548
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: Fukata Masaki 生理学研究所, 分子細胞生理研究領域, 教授 (00335027)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: 自己免疫性脳炎 / LGI1 / GABAa受容体 / 組換え抗体 / シナプス / けいれん

Outline of Final Research Achievements

Autoimmune encephalitis presenting with amnesia, seizures, and disorientation is highly topical in basic and clinical neuroscience. Recent studies have identified numerous associated autoantibodies, targeting synaptic proteins including neurotransmitter receptors and a secreted protein, LGI1. Here, by collaborating with Germany group, we isolated various recombinant monoclonal antibodies from patients' B cells with autoimmune encephalitis. Taking advantage of these antibodies, we elucidated patho-physiological mechanisms for autoimmune encephalitis.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

私共は、共同研究者のPruss博士らよって単離された組換え型モノクロナール抗体の中から、LGI1や、GABAa受容体、NMDA受容体に反応する自己抗体に関して、その反応特異性、抗原部位の同定、抗原-抗体間の親和性の評価等を行い、自己抗体の作用機序の解明に大きく貢献した。これらの研究成果は、Ann Neurol誌、PNAS誌、J Exp Med誌に国際共著論文として発表され、自己免疫性脳炎の病態解明に大きく貢献した。