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Metabolomics for biomarker discovery in systemic lupus erythematosus

Research Project

Project/Area Number 24591445
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionKobe University

Principal Investigator

SAEGUSA Jun  神戸大学, 医学部附属病院, 講師 (20514970)

Co-Investigator(Kenkyū-buntansha) MORINOBU Akio  神戸大学, 大学院医学研究科, 准教授 (10294216)
KAWANO Seiji  神戸大学, 医学部附属病院, 特命准教授 (20351512)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsメタボローム解析 / 全身性エリテマトーデス / バイオマーカー / ガスクロマトグラフィー質量分析計 / グルタミン酸 / 膠原病 / 関節リウマチ / メタボロミクス
Outline of Final Research Achievements

Metabolomics is the identification and quantification of the metabolome, all the low-molecular-weight metabolites in a biological sample. We examined the differences in the serum metabolome between patients with SLE and healthy subjects, using GC/MS. The levels of 25 metabolites were significantly different in SLE patients compared to healthy controls. The two-dimensional plot of the principal component analysis scores showed distinct clustering for the two subject groups. Multivariate statistical analysis revealed that variations in the levels of glutamic acid, urea, tyrosine, phosphate and glycerol greatly contributed to the observed separation of the metabolomics profiles of the SLE patients and healthy controls. The serum levels of glutamic acid were significantly correlated with the SLE disease activity index score in the patient group. These findings suggest that GC/MS-based serum metabolomics can serve as a novel diagnostic and monitoring tool for autoimmune diseases.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (30 results)

All 2015 2014 2013 2012

All Journal Article (10 results) (of which Peer Reviewed: 9 results,  Open Access: 1 results) Presentation (19 results) (of which Invited: 1 results) Book (1 results)

  • [Journal Article] Tofacitinib facilitates the expansion of myeloid-derived suppressor cells and ameliorates arthritis in SKG mice.2015

    • Author(s)
      Nishimura K, Saegusa J, Matsuki F, Akashi K, Kageyama G, Morinobu A
    • Journal Title

      Arthritis Rheumatol

      Volume: 67 Issue: 4 Pages: 893-902

    • DOI

      10.1002/art.39007

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-124 inhibits the progression of adjuvant-induced arthritis in rats.2015

    • Author(s)
      Nakamachi Y, Ohnuma K, Uto K, Noguchi Y, Saegusa J, Kawano S
    • Journal Title

      Ann Rheum Dis

      Volume: 印刷中 Issue: 3 Pages: 601-608

    • DOI

      10.1136/annrheumdis-2014-206417

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 自己免疫疾患のメタボローム解析の未来~新規バイオマーカーの同定と病態解明を目指して~2015

    • Author(s)
      三枝淳、河野誠司、森信暁雄
    • Journal Title

      臨床病理

      Volume: 63 Pages: 498-505

    • Related Report
      2014 Annual Research Report
  • [Journal Article] CD45RA-Foxp3low non-regulatory T cells in the CCR7-CD45RA-CD27+CD28+ effector memory subset are increased in synovial fluid from patients with rheumatoid arthritis2014

    • Author(s)
      Matsuki F, Saegusa J, Nishimura K, Miura Y, Kurosaka M, Kumagai S, Morinobu A
    • Journal Title

      Cell Immunol

      Volume: 290 Issue: 1 Pages: 96-101

    • DOI

      10.1016/j.cellimm.2014.05.011

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GC/MS-based metabolomics detects metabolic alterations in serum from SLE patients.2014

    • Author(s)
      Saegusa J, Irino Y, Yoshida M, Tanaka S, Kogata Y, Kageyama G, Tsuji G, Takenawa T, Kawano S, Kumagai S, Morinobu A
    • Journal Title

      Clin Exp Rheumatol

      Volume: 32 Pages: 148-148

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD45RA-Foxp3high activated/effector regulatory T cells in the CCR7+CD45RA-CD27+CD28+ central memory subset are decreased in peripheral blood from patients with rheumatoid arthritis.2013

    • Author(s)
      23. Matsuki F, Saegusa J, Miyamoto Y, Misaki K, Kumagai S, Morinobu A
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 438 Issue: 4 Pages: 778-183

    • DOI

      10.1016/j.bbrc.2013.05.120

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Podoplanin is an inflammatory protein upregulated in Th17 cells in SKG arthritic joints.2013

    • Author(s)
      Miyamoto Y, Uga H, Tanaka S, Kadowaki M, Ikeda M, Saegusa J, Morinobu A, Kumagai S, Kurata H.
    • Journal Title

      Mol Immunol.

      Volume: 54 Issue: 2 Pages: 199-207

    • DOI

      10.1016/j.molimm.2012.11.013

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mycophenolate mofetil versus intravenous cyclophosphamide for induction treatment of proliferative lupus nephritis in a Japanese population: a retrospective study2013

    • Author(s)
      Onishi A, Sugiyama D, Tsuji G, Nakazawa T, Kogata Y, Tsuda K, Naka I, Nishimura K, Misaki K, Kurimoto C, Hayashi H, Kageyama G, Saegusa J, Sugimoto T, Kawano S, Kumagai S, Morinobu A
    • Journal Title

      Mod Rheumatol

      Volume: 23(1) Issue: 1 Pages: 89-96

    • DOI

      10.1007/s10165-012-0634-9

    • NAID

      10031167670

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Dominant-Negative FGF1 Mutant (the R50E Mutant) Suppresses Tumorigenesis and Angiogenesis.2012

    • Author(s)
      Mori S.
    • Journal Title

      PLoS One.

      Volume: 8(2) Issue: 2 Pages: 20-36

    • DOI

      10.1371/journal.pone.0057927

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tumor necrosis factor-α inhibitor-induced antiglomerular basement membrane antibody disease in a patient with rheumatoid arthritis.2012

    • Author(s)
      Nishimura K, Saegusa J, Kawano S, Morinobu A.
    • Journal Title

      J Rheumatol.

      Volume: 39 Issue: 9 Pages: 1904-5

    • DOI

      10.3899/jrheum.120325

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 血清メタボロミクスによる全身性エリテマトーデスの新規バイオマーカーの探索2014

    • Author(s)
      三枝 淳, 河野 誠司, 辻 剛, 熊谷 俊一, 森信 暁雄
    • Organizer
      第61回日本臨床検査医学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2014-11-22 – 2014-11-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 自己免疫疾患のメタボローム解析の未来~新規バイオマーカーの同定と病態解明を目指して~2014

    • Author(s)
      三枝淳
    • Organizer
      日本臨床検査医学会 第57回近畿支部総会
    • Place of Presentation
      神戸
    • Year and Date
      2014-09-20 – 2014-09-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] シェーグレン症候群患者の唾液メタボロミクス2014

    • Author(s)
      蔭山 豪一, 三枝 淳, 田中 姿乃, 大西 輝, 古形 芳則, 森信 暁雄
    • Organizer
      第23回日本シェーグレン症候群学会学術集会
    • Place of Presentation
      長崎
    • Year and Date
      2014-09-12 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Clinical Features of 127 patients with Behcet’s disease in Japan.2013

    • Author(s)
      Nishimura K, Saegusa J, Sendo S, Kogata Y, Kageyama G, Kawano S, Kumagai S, Morinobu A
    • Organizer
      American College of Rheumatology 77th Annual Scientific Meeting
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Serum cytokine/chemokine profiles are useful for evaluating pathological conditions of rheumatoid arthritis and diagnosing anti-CCP antibody-negative patients.2013

    • Author(s)
      Uga H, Okazawa T, Miyamoto Y, Hasegawa T, Saegusa J, Tsuji G, Sendo S, Morinobu A, Kumagai S, Kurata H
    • Organizer
      American College of Rheumatology 77th Annual Scientific Meeting
    • Place of Presentation
      San Diego, CA
    • Related Report
      2013 Research-status Report
  • [Presentation] 自己抗原SS-A/Ro52はBcl-2の発言を低下させることにより細胞のアポトーシスを促進する2012

    • Author(s)
      Jauharoh Siti Nur Aisyah、三枝 淳、笠木 伸平、杉山 大典、栗本 千代、中町 祐司、信原 由実子、杉本 健、森信 暁雄、熊谷 俊一、河野 誠司
    • Organizer
      第56回日本リウマチ学会総会・学術集会・第21回国際リウマチシンポジウムプログラム
    • Place of Presentation
      グランドプリンスホテル新高輪(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] 関節リウマチの治療 DMARDs・NSAIDs(3)遺伝子多型に基づくサラゾスルファピリジン(SASP)の有効的使用法 関節リウマチの個別化医療2012

    • Author(s)
      熊谷 俊一、萩原 慶明、千藤 荘、岡田 信彦、杉山 大典、三枝 淳、辻 剛
    • Organizer
      第56回日本リウマチ学会総会・学術集会・第21回国際リウマチシンポジウムプログラム
    • Place of Presentation
      グランドプリンスホテル新高輪(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] 生物学的製剤(TNF阻害薬)無効アダリムマブ(ADA)投与RA患者における抗アダリムマブ抗体(AAA)産生と血中ADA濃度および効果の関係(追加報告)2012

    • Author(s)
      辻 剛、河野 誠司、森信 暁雄、三枝 淳、杉山 大典、八木田 正人、旗智 さおり、波内 俊三、信原 由実子、中澤 隆、中村 知子、岡田 信彦、千藤 荘、熊谷 俊一
    • Organizer
      第56回日本リウマチ学会総会・学術集会・第21回国際リウマチシンポジウムプログラム
    • Place of Presentation
      グランドプリンスホテル新高輪(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] 4つの表面マーカーを用いた新規分類法によるRAの病原性CD4陽性T細胞の探求2012

    • Author(s)
      松木 郁親、三枝 淳、宮本 佳昭、三崎 健太、河野 誠司、熊谷 俊一、森信 暁雄
    • Organizer
      第56回日本リウマチ学会総会・学術集会・第21回国際リウマチシンポジウムプログラム
    • Place of Presentation
      グランドプリンスホテル新高輪(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] Th17細胞はSKG関節炎モデルマウスの病態形成に関与する2012

    • Author(s)
      宮本 佳昭、田中 聡、池田 昌郁、宇賀 均、三枝 淳、森信 暁雄、熊谷 俊一、倉田 寛一
    • Organizer
      第22回日本サイトメトリー学会学術集会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Related Report
      2012 Research-status Report
  • [Presentation] 4つの表面マーカーを用いた新規分類法によるRAの病原性 CD4陽性T細胞の探求2012

    • Author(s)
      松木 郁親、三枝 淳、熊谷 俊一、森信 暁雄
    • Organizer
      第33回日本炎症・再生医学会
    • Place of Presentation
      ホテル日航福岡(福岡)
    • Related Report
      2012 Research-status Report
  • [Presentation] 関節リウマチの病態に関与するCD4陽性T細胞サブセットの同定2012

    • Author(s)
      松木 郁親、三枝 淳、熊谷 俊一、森信 暁雄
    • Organizer
      第40回日本臨床免疫学会総会
    • Place of Presentation
      京王プラザホテル(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] Th17細胞はSKG関節炎モデルマウスの病態形成に関与する2012

    • Author(s)
      宮本 佳昭、田中 聡、池田 雅郁、宇賀 均、三枝 淳、森信 暁雄、熊谷 俊一、倉田 寛一
    • Organizer
      第40回日本臨床免疫学会総会
    • Place of Presentation
      京王プラザホテル(東京)
    • Related Report
      2012 Research-status Report
  • [Presentation] 遺伝子多型に基づくサラゾスルファピリジン(SASP)の有効性の検討 関節リウマチの個別化医療2012

    • Author(s)
      萩原 慶明、辻 剛、千藤 荘、岡田 信彦、一瀬 良英、三枝 淳、熊谷 俊一
    • Organizer
      第59回日本臨床検査医学会 学術集会
    • Place of Presentation
      国立京都国際会館(京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] Early Growth Response-1(EGR-1)Controls Synoviocyte Apoptosis, and Its Expression is Regulated by the Direct Binding of Fibroblast Growth Factor-1(FGF1)or Insulin-Like Growth Factor-1(IGF1) to Integrin αvβ3.2012

    • Author(s)
      Shino Tanaka, Jun Saegusa, Seiji Kawano, Yoshikazu Takada, Shunichi Kumagai and Akio Morinobu
    • Organizer
      第76回アメリカリウマチ学会
    • Place of Presentation
      Walter E Washington Convention Center(米国・ワシントン)
    • Related Report
      2012 Research-status Report
  • [Presentation] Immediate Early Response Gene X-1 is Over-expressed and Regulates Apoptosis and Cytokine Production in Rheumatoid Arthritis Synovial Fibroblasts2012

    • Author(s)
      Akio Morinobu, Masaaki Fujita, Shino Tanaka, Jun Saegusa and Shunichi Kumagai
    • Organizer
      第76回アメリカリウマチ学会
    • Place of Presentation
      Walter E Washington Convention Center(米国・ワシントン)
    • Related Report
      2012 Research-status Report
  • [Presentation] Serum Metabolomics As a Novel Diagnostic Approach for Systemic Lupus Erythematosus.2012

    • Author(s)
      Jun Saegusa, Yasuhiro Irino, Masaru Yoshida, Shino Tanaka, Yoshinori Kogata, Goichi Kageyama, Seiji Kawano, Goh Tsuji, Shunichi Kumagai and Akio Morinobu
    • Organizer
      第76回アメリカリウマチ学会
    • Place of Presentation
      Walter E Washington Convention Center(米国・ワシントン)
    • Related Report
      2012 Research-status Report
  • [Presentation] Immediate Early Response Gene X-1 is Over-expressed and Regulates Apoptosis and Cytokine Production in Rheumatoid Arthritis Synovial Fibroblasts2012

    • Author(s)
      Akio Morinobu, Jun Saegusa, Shino Tanaka, Shunichi Kumagai
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Related Report
      2012 Research-status Report
  • [Presentation] Regulatory and Pro-Inflammatory Properties of CD4+ T-Cell Subsets Defined by CD45RA, CCR7, CD27, and CD28 in Patients with Rheumatoid Arthritis2012

    • Author(s)
      Fumichika Matsuki, Jun Saegusa, Yoshiaki Miyamoto, Keisuke Nishimura, Shino Tanaka, Shunichi Kumagai, Akio Morinobu
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(神戸)
    • Related Report
      2012 Research-status Report
  • [Book] 最新関節リウマチ学2014

    • Author(s)
      三枝淳,松木郁親,森信暁雄
    • Total Pages
      5
    • Publisher
      日本臨牀社
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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