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A potential biomaker with circulating auto-antibodies for cardiovascular disease in patients with obstructive sleep apnea

Research Project

Project/Area Number 16K09528
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionChiba University

Principal Investigator

Terada Jiro  千葉大学, 医学部附属病院, 講師 (20400898)

Co-Investigator(Kenkyū-buntansha) 日和佐 隆樹  千葉大学, 大学院医学研究院, 特任准教授 (30260251)
Research Collaborator Tatsumi Koichiro  
Matsumura Takuma  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords睡眠呼吸障害 / 動脈硬化 / 自己抗体 / バイオマーカー / 睡眠時無呼吸症候群 / 自己抗体マーカー / 呼吸器内科学
Outline of Final Research Achievements

In the present study, we identified two autoantibodies as potential novel biomarkers of atherosclerosis. In the first study, we discovered that COPE-Ab levels were significantly higher in patients with OSA, particularly those with moderate to severe OSA. Furthermore, patients with OSA and also CVD and/or stroke, hypertension, and a high BMI had elevated levels of COPE-Ab. Second, an elevated COPE-Ab level was the significant predictor of a history of CVD and/or stroke in a multivariate analysis of patients with OSA. The major finding of the second study was that neuroblastoma1(NBL1)-Ab level was significantly elevated in patients with both OSA and ACS compared with HVs. Subgroup analyses showed that NBL1-Ab level was significantly higher in patients with severe OSA and OSA patients with a past history of CAD. According to our results, COPE-Ab and NBL1-Ab might therefore be a biomarker of the risk of cardiovascular and cerebrovascular events in patients with OSA.

Academic Significance and Societal Importance of the Research Achievements

本研究で示したような,閉塞性無呼吸症候群(OSA)患者の血清で同定できる特異的な心血管疾患マーカーが明らかになれば,臨床に直接関連する動脈硬化を簡便に評価できる検査となることが期待される.特に,どのようなOSA患者が数年~数十年後に脳梗塞、心筋梗塞が発症するリスクがあるかを定量的に予測することが可能となれば,本疾患の治療アルゴリズムに寄与する可能性が考えられる.近年,数多くのバイオマーカーが実臨床で用いられているが,抗体マーカーは,抗原マーカーや酵素マーカーと比較すると非常に安定した測定結果が得られることが特徴であるため,将来臨床応用が可能な非侵襲的な検査となることが期待される.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (6 results)

All 2019 2018 2017 2016

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1): A potential biomarker for coronary artery disease in patients with obstructive sleep apnea.2018

    • Author(s)
      Matsumura T, Terada J, Kinoshita T, Sakurai Y, Yahaba M, Tsushima K, Sakao S, Nagashima K, Ozaki T, Kobayashi Y, Hiwasa T, Tatsumi K.
    • Journal Title

      PLOS One

      Volume: 13 Issue: 3 Pages: 1-1

    • DOI

      10.1371/journal.pone.0195015

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Circulating anti-coatomer protein complex subunit epsilon (COPE) autoantibodies as a potential biomarker for cardio- and cerebro-vascular events in patients with obstructive sleep apnea2017

    • Author(s)
      Matsumura T, Terada J, Kinoshita T, Sakurai Y, Yahaba M, Ema R, Amata A, Sakao S, Nagashima K, Tatsumi K, Hiwasa T
    • Journal Title

      J Clin Sleep Med

      Volume: 13 Issue: 03 Pages: 393-400

    • DOI

      10.5664/jcsm.6488

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 閉塞性睡眠時無呼吸患者における心血管障害のバイオマーカーとしての抗SNX16抗体の可能性2019

    • Author(s)
      勝俣雄介, 寺田二郎, 越川謙, 木下拓, 坂尾誠一郎, 巽浩一郎, 日和佐隆樹
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 閉塞性睡眠時無呼吸症患者における心血管障害のバイオマーカーとしての抗NBL1抗体の可能性2018

    • Author(s)
      松村 琢磨、寺田 二郎、木下 拓、櫻井 由子 矢幅 美鈴、坂尾 誠一郎、巽 浩一郎
    • Organizer
      睡眠呼吸障害研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Autoantibody against NBL1 in obstructive sleep apnea patients with cardiovascular disease2017

    • Author(s)
      Takuma Matsumura, Jiro Terada, Taku Kinoshita, Yoriko Sakurai, Reiko Kunii, Seiichiro Sakao, Koichiro Tatsumi
    • Organizer
      European Respirtory Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 睡眠時無呼吸症候群診療の多面性 血清抗体を用いた閉塞性睡眠時無呼吸症候群の脳・心血管イベント発症予測マーカー2016

    • Author(s)
      寺田二郎
    • Organizer
      日本臨床学会総会
    • Place of Presentation
      東京都・千代田区,砂防会館
    • Year and Date
      2016-10-28
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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