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Basic and clinical strategy to overcome microscopic polyangiitis

Research Project

Project/Area Number 26293082
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionHokkaido University

Principal Investigator

Ishizu Akihiro  北海道大学, 保健学研究科, 教授 (60321957)

Co-Investigator(Kenkyū-buntansha) 外丸 詩野  北海道大学, 医学(系)研究科(研究院), 准教授 (20360901)
Co-Investigator(Renkei-kenkyūsha) Arimura Yoshihiro  杏林大学, 医学部, 教授 (40222765)
Sada Ken-ei  岡山大学, 大学院医歯薬学総合研究科, 講師 (70423308)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords顕微鏡的多発血管炎 / 好中球細胞外トラップ / PAD阻害薬 / 治療反応性予測 / MPO-ANCA / MPO-ANCA関連血管炎 / 動物モデル / 炎症 / PAD4 / Cl-amidine / 病理学
Outline of Final Research Achievements

In vitro neutrophil extracellular trap (NET) formation was inhibited significantly by a peptidylarginine deiminase (PAD) inhibitor Cl-amidine. Serum MPO-ANCA titers of mice given Cl-amidine were significantly lower than those of control mice. The amounts of peritoneal NETs in the mice given Cl-amidine was significantly smaller than those in control mice.
Response to remission induction therapy can be predicted by monitoring the altered expressions of the 16 genes, including IRF7, IFIT1, IFIT5, OASL, CLC, GBP-1, PSMB9, HERC5, CCR1, CD36, MS4A4A, BIRC4BP, PLSCR1, DEFA1/DEFA3, DEFA4, and COL9A2, in the peripheral blood at an early point of treatment in MPA patients with high sensitivity (85.7%) and specificity (96.9%).

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (34 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (15 results) (of which Int'l Joint Research: 3 results,  Invited: 7 results) Remarks (7 results)

  • [Int'l Joint Research] Julius-Maximilians-Universitat Wurzburg(Germany)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Peptidylarginine deiminase inhibitor suppresses neutrophil extracellular trap formation and MPO-ANCA production.2016

    • Author(s)
      Kusunoki Y, Nakazawa D, Shida H, Hattanda F, Miyoshi A, Masuda S, Nishio S, Tomaru U, Atsumi T, Ishizu A.
    • Journal Title

      Frontiers in Immunology

      Volume: 7 Pages: 227-227

    • DOI

      10.3389/fimmu.2016.00227

    • NAID

      120005768817

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The presence of anti-lactoferrin antibodies in a subgroup of eosinophilic granulomatosis with polyangiitis patients and their possible contribution to enhancement of neutrophil extracellular trap formation.2016

    • Author(s)
      Shida H, Nakazawa D, Tateyama Y, Miyoshi A, Kusunoki Y, Hattanda F, Masuda S, Tomaru U, Kawakami T, Atsumi T, Ishizu A
    • Journal Title

      Frontiers in Immunology

      Volume: 7 Pages: 636-636

    • DOI

      10.3389/fimmu.2016.00636

    • NAID

      120005907000

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The responses of macrophages in interaction with neutrophils that undergo NETosis2016

    • Author(s)
      Nakazawa D, Shida H, Kusunoki Y, Miyoshi A, Nishio S, Tomaru U, Atsumi T, Ishizu A
    • Journal Title

      J Autoimmun

      Volume: Feb;67 Pages: 19-28

    • DOI

      10.1016/j.jaut.2015.08.018

    • NAID

      120005743065

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Establishment of a vascular endothelial cell-reactive type II NKT cell clone from a rat model of autoimmune vasculitis.2015

    • Author(s)
      Iinuma C, Waki M, Kawakami A, Yamaguchi M, Tomaru U, Sasaki N, Masuda S, Matsui Y, Iwasaki S, Baba T, Kasahara M, Yoshiki T, Paletta D, Herrmann T, Ishizu A.
    • Journal Title

      Int Immunol.

      Volume: 27 Issue: 2 Pages: 105-114

    • DOI

      10.1093/intimm/dxu088

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fatal cardiac small-vessel involvement in ANCA-associated vasculitis: an autopsy case report.2015

    • Author(s)
      Iwasaki S, Suzuki A, Fujisawa T, Sato T, Shirai S, Kamigaki M, Otsuka N, Tomaru U, Ishizu A.
    • Journal Title

      Cardiovasc Pathol.

      Volume: 24(6) Issue: 6 Pages: 408-410

    • DOI

      10.1016/j.carpath.2015.07.005

    • NAID

      120005905594

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible linkage between microscopic polyangiitis and thrombosis via neutrophil extracellular traps.2014

    • Author(s)
      Imamoto T, Nakazawa D, Shida H, Suzuki A, Otsuka N, Tomaru U, Ishizu A
    • Journal Title

      Clin Exp Rheumatology

      Volume: 32 Pages: 149-150

    • NAID

      120005397871

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced formation and disordered regulation of NETs in MPO-ANCA-associated microscopic polyangiitis2014

    • Author(s)
      Nakazawa D, Shida H, Tomaru U, Yoshida M, Nishio S, Atsumi T, Ishizu A.
    • Journal Title

      Journal of the American Society of Nephrology

      Volume: Epub Issue: 5 Pages: 990-997

    • DOI

      10.1681/asn.2013060606

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overexpression of TNF-α converting enzyme promotes adipose tissue inflammation and fibrosis induced by high fat diet.2014

    • Author(s)
      Matsui Y, Tomaru U, Miyoshi A, Ito T, Fukaya S, Miyoshi H, Atsumi T, Ishizu A.
    • Journal Title

      Exp Mol Pathol.

      Volume: 97(3) Issue: 3 Pages: 354-358

    • DOI

      10.1016/j.yexmp.2014.09.017

    • NAID

      120005476093

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 血管炎の発症機序とNETs2014

    • Author(s)
      中沢大悟,西尾妙織,外丸詩野,渥美達也,石津明洋.
    • Journal Title

      日本腎臓学会誌

      Volume: 56 Pages: 117-123

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 抗好中球細胞質抗体(ANCA)関連血管炎の病態と治療の最前線2014

    • Author(s)
      山村昌弘,佐田憲映,針谷正祥,藤井隆夫,石津明洋,有村義宏,槇野博史
    • Journal Title

      日本内科学会雑誌

      Volume: 103 Pages: 2012-2129

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 好中球細胞外トラップの異常とMPO-ANCA関連血管炎2014

    • Author(s)
      石津明洋
    • Journal Title

      日本小児腎臓病学会雑誌

      Volume: 27 Pages: 81-85

    • NAID

      130005067562

    • Related Report
      2014 Annual Research Report
  • [Presentation] The effect of peptidylarginine deiminase inhibitor on NET formation and MPO-ANCA production in mouse model2017

    • Author(s)
      Kusunoki Y, Nakazawa D, Shida H, Hattanda F, Miyoshi A, Masuda S, Nishio S, Tomaru U, Atsumi T, Ishizu A
    • Organizer
      The 18th International Vasculitis and ANCA Workshop
    • Place of Presentation
      東京大学伊藤国際学術研究センター(東京都文京区)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 皮膚科領域でみる血管炎の病理組織像からのアプローチ2016

    • Author(s)
      石津明洋
    • Organizer
      第46回日本皮膚アレルギー・接触皮膚炎学会総会学術大会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2016-11-05
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 血管炎新分類(CHCC2012)と皮膚血管炎の位置づけ―病理医の視線で2016

    • Author(s)
      石津明洋
    • Organizer
      第115回日本皮膚科学会総会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2016-06-04
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ANCA関連血管炎の臨床病理学的特徴と好中球細胞外トラップNETs2016

    • Author(s)
      石津明洋
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-05-12
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Peptidylarginine deiminase 4阻害薬は好中球細胞外トラップの形成阻害を介してMPO-ANCA産生を抑制する2016

    • Author(s)
      楠 由宏,中沢大悟,志田玄貴,八反田文彦,益田紗季子,外丸詩野,西尾妙織,渥美達也,石津明洋
    • Organizer
      第60回日本リウマチ学会総会・学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] 抗ラクトフェリン抗体は好酸球性多発血管炎性肉芽腫症において好中球細胞外トラップの形成を促進し,疾患活動性に関与する2016

    • Author(s)
      志田玄貴,中沢大悟,八反田文彦,楠 由宏,益田紗季子,外丸詩野,川上民裕,渥美達也,石津明洋
    • Organizer
      第60回日本リウマチ学会総会・学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Macrophages transiently reinforce neutrophil extracellular trap (NET)-related immunity and thereafter remove neutrophils that undergo NETosis.2015

    • Author(s)
      Ishizu A, Nakazawa D, Shida H, Kusunoki Y, Miyoshi A, Nishio S, Tomru U, Atsumi T.
    • Organizer
      第44回日本免疫学会総会・学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Identification of autoantigen recognized by rat vascular endothelial cell-reactive vasculitis-inducible type II NKT cell clone.2015

    • Author(s)
      Nishioka Y, Yamaguchi M, Kawakami A, Munehiro M, Tomaru U, Ishizu A.
    • Organizer
      第44回日本免疫学会総会・学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] MPO-ANCA関連血管炎におけるNETs-ANCA悪循環2015

    • Author(s)
      石津明洋
    • Organizer
      第59回日本リウマチ学会総会・学術集会シンポジウム「ANCA関連血管炎のUpdate」
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 抗ラクトフェリン抗体の病原性2015

    • Author(s)
      志田玄貴,中沢大悟,外丸詩野,川上民裕,渥美達也,石津明洋.
    • Organizer
      第59回日本リウマチ学会総会・学術集会ワークショップ「血管炎」
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] NETs-ANCA vicious cycle in MPO-ANCA-associated vasculitis.2015

    • Author(s)
      Ishizu A, Nakazawa D, Shida H, Kusunoki Y, Miyohi A, Nishio S, Tomaru U, Atsumi T, Yoshid M.
    • Organizer
      17th International Vasculitis and ANCA Workshop
    • Place of Presentation
      London (UK)
    • Year and Date
      2015-04-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Establishment of vascular endothelial cell-reactive type II NKT cell clone from rat model of autoimmune vasculitis.2015

    • Author(s)
      Ishizu A, Iinuma C, Waki M, Yamaguchi M, Kawakami A, Nishioka Y, Sasaki N, Tomaru U, Yoshiki T, Paletta D, Herrmann T.
    • Organizer
      17th International Vasculitis and ANCA Workshop
    • Place of Presentation
      London (UK)
    • Year and Date
      2015-04-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 血管炎症候群の分類と臨床病理2014

    • Author(s)
      石津明洋
    • Organizer
      第24回日本リウマチ学会北海道・東北支部学術集会ランチョンセミナー
    • Place of Presentation
      北海道大学医学部学友会館フラテ(札幌市)
    • Year and Date
      2014-11-22 – 2014-11-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 好中球細胞外トラップの異常とMPO-ANCA関連血管炎2014

    • Author(s)
      石津明洋
    • Organizer
      第49回日本小児腎臓病学会学術集会教育講演
    • Place of Presentation
      秋田ビューホテル(秋田市)
    • Year and Date
      2014-06-05 – 2014-06-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ANCAによる血管傷害機序2014

    • Author(s)
      石津明洋
    • Organizer
      第58回日本リウマチ学会総会・学術集会シンポジウム「ANCA関連血管炎のアップデート」
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都)
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Remarks] 北海道大学学術成果コレクション(HUSCAP)

    • URL

      http://hdl.handle.net/2115/62351

    • Related Report
      2016 Annual Research Report
  • [Remarks] 北海道大学学術成果コレクション(HUSCAP)

    • URL

      http://hdl.handle.net/2115/64033

    • Related Report
      2016 Annual Research Report
  • [Remarks] 北海道大学学術成果コレクション

    • URL

      http://eprints.lib.hokudai.ac.jp/dspace/handle/2115/59840

    • Related Report
      2015 Annual Research Report
  • [Remarks] 北海道大学学術成果コレクション

    • URL

      http://eprints.lib.hokudai.ac.jp/dspace/handle/2115/61171

    • Related Report
      2015 Annual Research Report
  • [Remarks] 北海道大学学術成果コレクション(HUSCAP)

    • URL

      http://eprints.lib.hokudai.ac.jp/dspace/handle/2115/54864

    • Related Report
      2014 Annual Research Report
  • [Remarks] 北海道大学学術成果コレクション(HUSCAP)

    • URL

      http://eprints.lib.hokudai.ac.jp/dspace/handle/2115/54674

    • Related Report
      2014 Annual Research Report
  • [Remarks] 北海道大学学術成果コレクション(HUSCAP)

    • URL

      http://eprints.lib.hokudai.ac.jp/dspace/handle/2115/57002

    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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