Elucidation of glycosylation form of nephritogenic IgA1 and dysregulation of mucosal immunity in IgA nephropathy
| Project/Area Number |
19K08733
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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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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 祐介 順天堂大学, 大学院医学研究科, 教授 (70372935)
鈴木 仁 順天堂大学, 医学部, 教授 (10468572)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | IgA腎症 / 分泌型IgA / 糖鎖異常IgA1 / 粘膜免疫異常 / Secretory IgA |
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| Outline of Research at the Start |
IgA腎症は世界で最も多い原発性糸球体腎炎であり、20年で約40%が末期腎不全に至る予後不良の疾患であるが、未だ病因の全容は不明であり確立された治療は存在しない。本研究は、IgA腎症患者由来の糖鎖異常IgA1ヒンジ部のO-結合型糖鎖の糖鎖構造や、糖鎖異常IgA1およびSecretory componentの由来臓器を解明し、口蓋扁桃摘出術およびステロイドパルス療法が治療効果をもたらすメカニズムの一部を明らかにし、分子標的治療の礎とすることを目的とする。
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| Outline of Final Research Achievements |
Aberrantly glycosylated IgA1 and antibodies directed against aberrantly glycosylated IgA1 has been considered as key molecules in the pathogenesis of IgA nephropathy (IgAN). Mucosae have been speculated as one of the major synthesis sites of aberrantly glycosylated IgA1, whereas it remains uncertain. In this study, we demonstrated the presence of secretory component (SC) in aberrantly glycosylated IgA1 purified from serum of patients with IgAN, indicating that aberrantly glycosylated IgA1 originates from mucosae. Our experiments also revealed that the intensity of deposition of SC in glomerulus is associated with the severity of hematuria, suggesting the involvement of SC in the progression of glomerulonephritis. We are now investigating detailed inflammation mechanisms mediated SC in glomerulus.
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| Academic Significance and Societal Importance of the Research Achievements |
今回我々の実験結果より、糖鎖異常IgA1の少なくとも一部が粘膜由来であり、腎糸球体へのSCの沈着の程度が血尿の重症度と関連していることが確認されており、粘膜由来の糖鎖異常IgA1が腎炎の発症・進展に関与していると考えられた。今回の結果は、糖鎖異常IgA1の産生源と考えられる粘膜をターゲットとした治療である口蓋扁桃摘出術や腸管免疫に特異的に作用するステロイド治療 (Budesonide)の理論的根拠になると思われる。現在、腎糸球体におけるSCを介した炎症惹起メカニズムにについて検証を行っているところである。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] Rituximab in Membranous Nephropathy2021
Author(s)
Philipp Gauckler, Jae Il Shin, Federico Alberici, Vincent Audard, Annette Bruchfeld, Martin Busch, Chee Kay Cheung, Matija Crnogorac, Elisa Delbarba, Kathrin Eller, Stanislas Faguer, Kresimir Galesic, Sian Griffin, Martijn W F van den Hoogen, Zdenka Hruskova, Anushya Jeyabalan, Masahiro Muto et al.
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Journal Title
Kidney International Reports
Volume: 6
Issue: 4
Pages: 881-893
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] A digest from evidence-based clinical practice guideline for IgA nephropathy 20202021
Author(s)
Hitoshi Suzuki, Masao Kikuchi, Kentaro Koike, Hiroyuki Komatsu, Keiichi Matsuzaki, Kazuo Takahashi, Daisuke Ichikawa, Masahiro Okabe, Yoko Obata, Ritsuko Katafuchi, Masao Kihara, Kaori Kohatsu, Takaya Sasaki, Akihiro Shimizu, Masahiro Muto, Hiroyuki Yanagawa, Yusuke Suzuki et al.
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Journal Title
Clinical and Experimental Nephrology
Volume: 25
Issue: 12
Pages: 1269-1276
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Apoptosis inhibitor of macrophage を介した腎糸球体の炎症起点の解明2022
Author(s)
加藤莉那, 本間望, 李明峰, 中山麻衣子, 深尾勇輔, 二瓶義人, 武藤正浩, 新井郷子, 鈴木仁, 宮崎徹, 鈴木祐介
Organizer
第45回IgA腎症研究会学術集会
Related Report
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