Clarify the pathological mechanism for autoimmune encephalitis using recombinant autoantibodies
Project/Area Number |
19K22548
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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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)
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Project Period (FY) |
2019-06-28 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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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 / 記憶障害 |
Outline of Research at the Start |
自己免疫性脳炎は、けいれん、記憶障害、見当識障害など多様な症状を示す重篤な脳疾患である。最近、私共を含めた研究により、様々なシナプス蛋白質(NMDA受容体、LGI1、GABA受容体等)に対する自己抗体が次々と同定されてきた。本研究では、患者由来の組換え型自己抗体を活用し、分子、神経細胞、神経回路、動物個体レベルでの標的蛋白質の生理機能や自己抗体の病態機構を明らかにしていく。
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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.
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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。
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Report
(4 results)
Research Products
(49 results)
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[Journal Article] 14-3-3 proteins stabilize LGI1-ADAM22 levels to regulate seizure thresholds in mice2021
Author(s)
Norihiko Yokoi, Yuko Fukata, Kei Okatsu, Atsushi Yamagata, Yan Liu , Makoto Sanbo, Yuri Miyazaki, Teppei Goto, Manabu Abe , Hidetoshi Kassai, Kenji Sakimura, Dies Meijer, Masumi Hirabayashi, Shuya Fukai, Masaki Fukata
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Journal Title
Cell Reports
Volume: 37
Issue: 11
Pages: 110107-110107
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice2021
Author(s)
Yoshida T, Yamagata A, Imai A, Kim J, Izumi H, Nakashima S, Shiroshima T, Maeda A, Iwasawa-Okamoto S, Azechi K, Osaka F, Saitoh T, Maenaka K, Shimada T, Fukata Y, Fukata M, Matsumoto J, Nishijo H, Takao K, Tanaka S, Okabe S, Tabuchi K, Uemura T, Mishina M, Mori H & Fukai S
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Journal Title
Nature Communications
Volume: 12(1)
Issue: 1
Pages: 1848-1848
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Targeting CCR5 trafficking to inhibit HIV-1 infection2019
Author(s)
Boncompain Gaelle、Herit Floriane、Tessier Sarah、Lescure Aurianne、Del Nery Elaine、Gestraud Pierre、Staropoli Isabelle、Fukata Yuko、Fukata Masaki、Brelot Anne、Niedergang Florence、Perez Franck
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Journal Title
Science Advances
Volume: 5
Issue: 10
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Limbic Encephalitis in a Cat with Hippocampal Necrosis, putatively associated with DCC (deleted in colorectal cancer; Netrin-1 Receptor) Antibodies2019
Author(s)
Hasegawa D, Ohnishi Y, Koyama E, Matsunaga S, Ohtani S, Nakanishi A, Shiga T, Chambers JK, Uchida K, Yokoi N, Fukata Y, Fukata M.
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Journal Title
J Vet Intern Med
Volume: 印刷中
Issue: 3
Pages: 1440-1445
DOI
Related Report
Peer Reviewed
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