analysis of newly target auto antigens in autoimmune encephalitis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461286
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kagoshima University
• Principal Investigator: Watanabe Osamu 鹿児島大学, 医歯学域 医学部・歯学部附属病院, 講師 (30511802)
• Co-Investigator(Kenkyū-buntansha): KISHIDA Shosei 鹿児島大学, 学術研究院 医歯学域医学系, 教授 (50274064) ; Takashima Hiroshi 鹿児島大学, 学術研究院 医歯学域医学系, 教授 (80372803)
• Co-Investigator(Renkei-kenkyūsha): Fukata Masaki 大学共同利用機関法人 自然科学研究機構, 生理学研究所, 教授 (00335027)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 標的抗原解析 / イオンチャネル / 自己抗体

Outline of Final Research Achievements

We established a potential molecular mechanism for the pathogenic role of antibodies to leucine-rich, glioma inactivated 1 (LGI1), which are found in patients with limbic encephalitis (an acquired autoimmune condition presenting with memory loss, temporal lobe seizures and personality change, associated with swelling and inflammation of the medial temporal lobe, with a good response to immunotherapies). LGI1 is a secreted protein that binds to both a disintegrin and metalloproteinase domain 23 (ADAM23) presynaptically, where it is a component of a ‘voltage-gated potassium channel (VGKC) complex’, and ADAM22 postsynaptically, where it interacts with AMPA receptors.
We show that the LGI1 antibodies from patients with limbic encephalitis interfere with the LGI1/ADAM22 interaction, leading to a loss of postsynaptic AMPA receptors. This is a novel finding, which begins to establish a mechanism of action for the LGI1 antibodies.

Free Research Field

神経免疫学