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Biomarker to predict treatment efficacy of MAC pulmonary disease

Research Project

Project/Area Number 17K10023
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionNagoya City University

Principal Investigator

Yutaka Ito  名古屋市立大学, 医薬学総合研究院(医学), 准教授 (80362482)

Co-Investigator(Kenkyū-buntansha) 新實 彰男  名古屋市立大学, 医薬学総合研究院(医学), 教授 (30252513)
Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsMycobacterium avium / LL-37 / 好中球 / IL-8 / 抗菌活性 / CT / 菌陰性化 / 非結核性抗酸菌 / 感染症 / 感染症診断学
Outline of Final Research Achievements

Among 18 patients of pulmonary MAC disease who received multidrug treatment for more than 12 months, LL-37 in bronchoalveolar lavage (BAL) was associated with improvement of CT findings, but not bacterial negative conversion. LL-37 in BAL was positively correlated with neutrophil rate and IL-8 in BAL. The improvement of CT findings was not associated with neutrophil rate and IL-8 in BAL, age, white blood cell counts and neutrophil counts in blood and CRP. LL-37 in BAL was the only biomarker to predict the improvement of CT findings. The MICs of MAC bacilli for clarithromycin, rifampicin, and ethambutol in the presence of LL-37 were significantly reduced. LL-37 enhanced antimicrobial effects.

Academic Significance and Societal Importance of the Research Achievements

LL-37は好中球から産生されると報告されており、MAC菌感染により惹起された気管支、肺内の好中球性炎症に関連して産生されたLL-37が、その抗菌薬の増強効果により画像所見の改善という臨床効果につながったと考えられ、LL-37は治療効果を予測するバイオマーカーになる可能性が示された。治療前喀痰培養陰性の軽症例が多く、菌陰性化との関連を示せなかったのが本研究の限界ではあるが、LL-37が低値で抗菌治療による画像所見の改善が乏しい症例でのLL-37補充療法という新たな治療の可能性をみいだした。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results)

  • [Journal Article] Association between Mycobacterium avium complex lung disease and serum vitamin D status, antimicrobial peptide levels, and bone mineral density.2018

    • Author(s)
      Fujita K, Ito Y, Oguma T, Mio T, Niimi A, Hirai T.
    • Journal Title

      Medicine (Baltimore).

      Volume: 97 Issue: 38 Pages: e12463-e12463

    • DOI

      10.1097/md.0000000000012463

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 抗菌ペプチドLL-37のMAC菌に対する抗菌活性について2018

    • Author(s)
      山羽悠介、伊藤 穣、鈴木克洋、菊地利明、小川賢二、長谷川直樹、藤内 智、倉島篤行、渡辺彰、新実彰男
    • Organizer
      第58回日本呼吸器学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 抗菌ペプチドLL-37のMAC菌に対する抗菌活性について2018

    • Author(s)
      山羽悠介、伊藤 穣、鈴木克洋、菊地利明、小川賢二、長谷川直樹、藤内 智、倉島篤行、渡辺彰、新実彰男
    • Organizer
      第93回日本結核病学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 抗菌ペプチドLL-37のMAC菌に対する抗菌活性について2018

    • Author(s)
      山羽悠介、伊藤 穣、鈴木克洋、菊地利明、小川賢二、長谷川直樹、藤内 智、倉島篤行、渡辺彰、新実彰男
    • Organizer
      第58回日本呼吸器学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 抗菌ペプチドLL-37のMAC菌に対する抗菌活性について2018

    • Author(s)
      山羽悠介、伊藤 穣、鈴木克洋、菊地利明、小川賢二、長谷川直樹、藤内 智、倉島篤行、渡辺彰、新実彰男
    • Organizer
      第93回日本結核病学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2023-01-30  

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