2018 Fiscal Year Final Research Report
Elucidation of the axonal degenerative mechanism focusing on the paranodal molecules in immune-mediated neuropathy
| Project/Area Number |
16K09693
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Nagoya University |
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Principal Investigator |
Iijima Masahiro 名古屋大学, 医学部附属病院, 特任講師 (40437041)
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| Co-Investigator(Kenkyū-buntansha) |
川頭 祐一 名古屋大学, 医学部附属病院, 病院講師 (40569779)
勝野 雅央 名古屋大学, 医学系研究科, 教授 (50402566)
小池 春樹 名古屋大学, 医学系研究科, 准教授 (80378174)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 慢性炎症性脱髄性多発根神経炎 / 前向きコホート / IgG4サブクラス自己抗体 / 傍ランヴィエ絞輪部 / 軸索-髄鞘間相互作用 / モデルマウス |
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| Outline of Final Research Achievements |
We have conducted a consortium called “CIDP-J” at 16 domestic universities for research of CIDP. More than 200 cases retrospectively and prospectively collected were registered during the research period. Clinical information such as age at onset, sex, progression type, INCAT score, R-ODS, grasp power, MRC score, responsiveness to each therapeutics have been collected. The breakdown of IgG4-subclass autoantibodies (NF155, CNTN1) that target paranode is newly clarified in this study, and it can be useful for future criteria and guideline as well as severity classification.
About NOD B7-2 knockout mice, which are expected as an inflammatory demyelinating model for CIDP, are characterized by progressive posterior weakness with severe infiltration of macrophages as well as lymphocytes in PNS. We analyzed the natural history and fluctuation of the infiltration over time, it leads to the elucidation of pathogenesis reflecting disease activity and irreversible axonal degeneration.
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| Free Research Field |
免疫介在性ニューロパチー
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| Academic Significance and Societal Importance of the Research Achievements |
国内症例をもとにしたIgG4サブクラス自己抗体陽性CIDPの疾患全体に占める割合は今まで明らかではなかったが、本研究（CIDP-J）によりその詳細な知見が得られた。自己抗体陽性例は既存治療、とくにIVIgへの反応性不良が示されたことから、本抗体は治療法選択に大きな影響を及ぼす。さらに抗体陽性例は細胞性免疫機序の関与が乏しく、傍ランヴィエ絞輪部の構造変化が電気生理学的脱髄を呈するなど治療法開発につながる学術的意義に相当する。
モデルマウスからCIDPの多様な病態を網羅しうる類似性が示され、新規候補薬の有効性検証はじめ、継時的に変化する各免疫担当細胞に着目した選択的治療薬開発の進展が期待される。
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