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Identification of nephritogenic abnormally glycosylated IgA1 and its application to point of care testing

Research Project

Project/Area Number 19K08691
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionFujita Health University

Principal Investigator

Takahashi Kazuo  藤田医科大学, 医学部, 教授 (90631391)

Co-Investigator(Kenkyū-buntansha) 湯澤 由紀夫  藤田医科大学, 医学部, 教授 (00191479)
坪井 直毅  藤田医科大学, 医学部, 教授 (50566958)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsIgA腎症 / 糖鎖異常IgA / バイオマーカー / 質量分析 / 糖鎖医学 / 糖鎖異常IgA1 / 迅速診断法 / プロテオミクス
Outline of Research at the Start

IgA腎症は,わが国に多い慢性糸球体腎炎で,20年の経過で約40%が末期腎不全に陥る。患者血液中に増加する糖鎖異常IgA1(Gd-IgA1; Gal-deficient-IgA1)は病因に深く関与する。本研究は,本症におけるGd-IgA1の役割の解明と診断への応用を目指し,①IgA腎症患者の沈着IgA1の糖鎖構造を同定,②Gd-IgA1の臨床的意義を検討,③迅速なGd-IgA1検出法の開発を行う。

Outline of Final Research Achievements

We aimed to develop a Point of Care Testing (POCT) by identifying detailed glycan structure of nephritogenic abnormally glycosylated IgA1 increasing specifically in IgA nephropathy (IgAN). We quantitatively profiled glycoforms of serum IgA1 derived from Japanese and Caucasian patients of IgAN and identified candidate glycoforms that are specifically increased in IgAN. We are currently generating monoclonal antibodies to specific glycoform to develop POCT.

Academic Significance and Societal Importance of the Research Achievements

日本人と白人のIgA腎症に共通のIgA1の糖鎖構造の特徴を同定した。新規診断薬の開発のみならず,糖鎖異常IgA1の産生機構の解明,さらには新規治療標的につながることが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (25 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (7 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (12 results) (of which Int'l Joint Research: 5 results) Remarks (2 results)

  • [Int'l Joint Research] University of Bari(イタリア)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Aristotle University of Thessaloniki(ギリシャ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Bari(イタリア)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of Alabama at Birmingham(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Galactose-Deficient IgA1 B cells in the Circulation of IgA Nephropathy Patients Carry Preferentially Lambda Light Chains and Mucosal Homing Receptors2022

    • Author(s)
      Zachova Katerina、Jemelkova Jana、Kosztyu Petr、Ohyama Yukako、Takahashi Kazuo、Zadrazil Josef、Orsag Jiri、Matousovic Karel、Galuszkova Dana、Petejova Nadezda、Mestecky Jiri、Raska Milan
    • Journal Title

      Journal of the American Society of Nephrology

      Volume: 33 Issue: 5 Pages: 908-917

    • DOI

      10.1681/asn.2021081086

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hepatocellular carcinoma induces body mass loss in parallel with osmolyte and water retention in rats2022

    • Author(s)
      Kidoguchi Satoshi、Kitada Kento、Nakajima Kazuki、Nakano Daisuke、Ohsaki Hiroyuki、Kittikulsuth Wararat、Kobara Hideki、Masaki Tsutomu、Yokoo Takashi、Takahashi Kazuo、Titze Jens、Nishiyama Akira
    • Journal Title

      Life Sciences

      Volume: 289 Pages: 120192-120192

    • DOI

      10.1016/j.lfs.2021.120192

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Aberrantly Glycosylated IgA1 in IgA Nephropathy: What We Know and What We Don’t Know2021

    • Author(s)
      Ohyama Yukako、Renfrow Matthew B.、Novak Jan、Takahashi Kazuo
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 16 Pages: 3467-3467

    • DOI

      10.3390/jcm10163467

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mass spectrometry for the identification and analysis of highly complex glycosylation of therapeutic or pathogenic proteins2020

    • Author(s)
      Ohyama.Y, Nakajima.K, Reinfow MB, Novak J. Takahashi K
    • Journal Title

      Expert Review of Proteomics

      Volume: 5 Issue: 4 Pages: 0-0

    • DOI

      10.1080/14789450.2020.1769479

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases2020

    • Author(s)
      Stewart Tyler J、Takahashi Kazuo、Xu Nuo、Prakash Amol、Brown Rhubell、Raska Milan、Renfrow Matthew B、Novak Jan
    • Journal Title

      Glycobiology

      Volume: - Issue: 5 Pages: 540-556

    • DOI

      10.1093/glycob/cwaa111

    • Related Report
      2020 Research-status Report
  • [Journal Article] Analysis of O-glycoforms of the IgA1 hinge region by sequential deglycosylation.2020

    • Author(s)
      Ohyama Y, Yamaguchi H, Nakajima K, Mizuno T, Fukamachi Y, Yokoi Y, Tsuboi N, Inaguma D, Hasegawa M, Renfrow MB, Novak J, Yuzawa Y, Takahashi K.
    • Journal Title

      Sci Rep.

      Volume: 10(1) Issue: 1 Pages: 671-671

    • DOI

      10.1038/s41598-020-57510-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IgA1 hinge-region clustered glycan fidelity is established early during semi-ordered glycosylation by GalNAc-T22019

    • Author(s)
      Stewart Tyler J、Takahashi Kazuo、Whitaker Robert H、Raska Milan、Placzek William J、Novak Jan、Renfrow Matthew B
    • Journal Title

      Glycobiology

      Volume: 29 Issue: 7 Pages: 543-556

    • DOI

      10.1093/glycob/cwz007

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] IgA1ヒンジ部O結合型糖鎖構造の人種間比較(日本人-ギリシャ人)2021

    • Author(s)
      大山友香子、山口央輝、Francesco P. Schena、坪井直毅、高橋和男
    • Organizer
      第44回 IgA腎症研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] Racial heterogeneity of IgA1 hinge region O glycoforms in patients with IgA nephropathy2020

    • Author(s)
      Yukako Ohyama, Samantha Chiurlia, Sharon N. Cox, Nikoletta Maria Kouri, Maria J Stangou, Hisateru Yamaguchi, Kazuki Nakajima, Daijo Inaguma, Midori Hasegawa, Yukio Yuzawa, Naotake Tsuboi, Aikaterini A. Papagianni, Francesco P. Schena, Kazuo Takahashi
    • Organizer
      ASN kidney week 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Longitudinal changes of IgA1 O-glycoforms in IgA nephropathy2020

    • Author(s)
      Yukako Ohyama, Hisateru Yamaguchi, Kazuki Nakajima, Daijo Inaguma, Midori Hasegawa, Naotake Tsuboi, Matthew B Renfrow, Jan Novak, Yukio Yuzawa, Kazuo Takahashi
    • Organizer
      57th ERA-EDTA
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Molecular Characterization of IgA1 in Patients with IgA Nephropathy2019

    • Author(s)
      Kazuo Takahashi
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Quantitative assessment of sites with galactose deficient O-glycans in the hinge region of IgA1.2019

    • Author(s)
      Yukako Ohyama, Hisateru Yamaguchi, Kazuki Nakajima, Hiroki Hayashi, Shigehisa Koide, Daijo Inaguma, Midori Hasegawa, Matthew B. Renfrow, Jan Novak, Yoshiyuki Hiki, Naotake Tsuboi, Yukio Yuzawa, Kazuo Takahashi.
    • Organizer
      Kidney Week 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Validation study of KM55 ELISA Kit in IgA Nephropathy IgAN patients for the detection of galactosedeficient IgA1 (Gd-IgA1) and corticosteroid therapy monitoring.2019

    • Author(s)
      Nikoletta-Maria Kouri, Maria Stangou, Samantha Chiurlia, Sharon Natasha Cox, Yukako Ohyama, Kazuo Takahashi, Aikaterini Papagianni, Francesco Paolo Schena.
    • Organizer
      Kidney Week 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comparison of IgA1 hinge-region O-glycoforms between patients with IgA nephropathy and healthy subjects.2019

    • Author(s)
      Yukako Ohyama, Kazuo Takahashi, Hisateru Yamaguchi, Shoko Matsushita, Kazuki Nakajima, Naotake Tsuboi, Inaguma Daijo, Hasegawa Midori, Matthew B Renfrow, Jan Novak, Yoshiyuki Hiki, Yuzawa Yukio.
    • Organizer
      ERA-EDTA 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] IgA1ヒンジ部O結合型糖鎖構造の患者健常者比較2019

    • Author(s)
      大山友香子,高橋和男,松下祥子,山口央輝,中嶋和紀,Matthew B. Renfrow,Jan Novak,比企能之,湯澤由紀夫
    • Organizer
      第42回IgA症研究会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] IgA1ヒンジ部O結合型糖鎖構造とGd-IgA値の患者健常者比較2019

    • Author(s)
      大山友香子,高橋和男,山口央輝,松下祥子,伊藤辰将,中嶋和紀, 林宏樹,小出滋久,坪井直毅,稲熊大城,長谷川みどり,湯澤由紀夫.
    • Organizer
      第62回日本腎臓学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 質量分析法を用いたIgA結合タンパク質のIgA腎症治療前後比較2019

    • Author(s)
      大山友香子,高橋和男,山口央輝,松下祥子,伊藤辰将,中嶋和紀,林宏樹,小出滋久,坪井直毅,稲熊大城,長谷川みどり,湯澤由紀夫
    • Organizer
      第62回日本腎臓学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] IgA腎症におけるPathogenic IgA1の構造同定の試み2019

    • Author(s)
      大山友香子,松下祥子,山口央輝,中嶋和紀,坪井直毅,高橋和男,湯澤由紀夫
    • Organizer
      第10回分子腎フォーラム
    • Related Report
      2019 Research-status Report
  • [Presentation] 糸球体腎炎に関わるタンパク質架橋化酵素の機能解明に向けた基礎的研究2019

    • Author(s)
      伊藤辰将、辰川英樹、山口央輝、髙橋和男、人見清隆、湯澤由紀夫
    • Organizer
      第62回腎臓学会総会
    • Related Report
      2019 Research-status Report
  • [Remarks] IgA腎症の病態解明

    • URL

      https://fujitabms.wordpress.com/%e7%a0%94%e7%a9%b6%e6%a6%82%e8%a6%81/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 藤田医科大学医学部解剖学II

    • URL

      https://www.fujita-hu.ac.jp/faculty/medicine/department/anatomyii.html

    • Related Report
      2020 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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