A novel therapy by targeting a key molecules pentraxin 3 involved in Kawasaki Disease
| Project/Area Number |
16K08422
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Aichi Gakuin University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
北川 好郎 愛知医科大学, 医学部, 講師 (00440719)
三鴨 廣繁 愛知医科大学, 医学部, 教授 (00262775)
馬場 礼三 中部大学, 生命健康科学部, 教授 (90287029)
武藤 太一朗 愛知医科大学, 医学部, 講師 (80613695)
太期 健二 日本医科大学, 先端医学研究所, 助教 (20466866)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | 川崎病 / ガンマグロブリン抵抗性 / Toxic shock 川崎病 / pentraxin 3 / 冠動脈病変 / バイオマーカー / パターン認識受容体 / ショットガンプロテオミクス / ガンマグロブリン / presepsin / NT-proBNP / 冠動脈瘤 / 血管炎 / ガンマグロブリン療法 / 血管内皮 / 炎症マーカー / 生体分子 / バイオテクノロジー / 蛋白質 / 薬学 / 臨床 |
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| Outline of Final Research Achievements |
Biomarker candidates were validated to establish a marker to discriminate the severity of Kawasaki disease (KD). The concentration of pentraxin 3, Presepsin, NT-proBNP, sLOX-1, MMP-9 was measured. The power of predictivity was compared by IVIG unresponsiveness or coronary artery sequelae. Plasma PTX3 level was significantly higher in IVIG non-responders than in IVIG responders (46±7.5 vs. 17±1.5 ng/ml, p< 0.001). The higher PTX3 levels he exhibited means an increased presence of coronary artery lesion (CAL) formation compared to cases without CAL (85±8.4 vs. 22±2.2 ng/ml, p< 0.0001) . When the cutoff value was set at 68.85 ng/ml of PTX3, specificity 98.21, sensitivity 100, and its likelihood ratio was 56 in coronary artery sequelae. This study clearly showed that serum levels of PTX3, activation marker of the innate immune system. The plasma PTX3 levels could be a useful biomarker in the clinical management of KD, especially for predicting responsiveness to IVIG and CAL formation.
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| Academic Significance and Societal Importance of the Research Achievements |
川崎病初期のペントラキシン 3 (PTX3) が25.6 ng/ml以上では、IVIG不応例となり、86.05 ng/ml以上では冠動脈瘤形成が必発であり、これ未満の症例では冠動脈瘤の発生がないことを明らかにした。PTX3が急性期冠動脈病変の程度も予測し、川崎病の重症度の層別化に有効であることが確認された。病初期のPTX3の高値は、10日以前の急性期病変の程度にも関連していた。これらの結果を元に、川崎病の発症病態として自然免疫系 PAMPsによる自然免疫の異常な活性化が大きな役割として 関与していると考えられた。川崎病でのNETs成分とPTX3の結合体の特定が、病因解明につながる可能性がある。
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Report
(5 results)
Research Products
(27 results)
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[Journal Article] Procalcitonin as a Biomarker of Unresponsiveness to Intravenous Immunoglobulin for Kawasaki Disease2020
Author(s)
Nakamura, N. Muto, T. Masuda, Y. Numoto, S. Kodama, S. Miyamoto, R. Miyata, K. Hayakawa, T. Mori, H. Kuroyanagi, Y. Akaihata, M. Iwayama, H. Kurahashi, H. Shimomura, Y. Nagai, T. Hori, T. Agata, H. Okumura, A.
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Journal Title
Pediatr Infect Dis J
Volume: 39
Pages: 483-491
Related Report
Peer Reviewed
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[Journal Article] 016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.2016
Author(s)
Ravelli A, Minoia F, Kitoh T, Lehmberg K, Lovell DJ, Miettunen P, Nichols KE, Ozen S, Pachlopnik Schmid J, Ramanan AV, Russo R, Schneider R, Sterba G, Uziel Y, Wallace C, Wouters C, Wulffraat N, Demirkaya E, Brunner H, Martini A, Ruperto N, Cron RQ
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Journal Title
Ann Rheum Dis.
Volume: 75
Issue: 3
Pages: 781-789
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Expert consensus on dynamics of laboratory tests for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.2016
Author(s)
Ravelli A, Minoia F, Kitoh T, Lehmberg K, Lovell D, Miettunen P, Nichols KE, Ozen S, Pachlopnik Schmid J, Ramanan AV, Russo R, Schneider R, Sterba G, Uziel Y, Wallace C, Wouters C, Wulffraat N, Demirkaya E, Brunner H, Martini A, Ruperto N, Cron RQ.
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Journal Title
RMD Open.
Volume: 2
Issue: 1
Pages: e000161-e000161
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Change in codeine prescription rate after Japanese Ministry of Health and Labor to request usage limitation to under twelve years old children in July 20172018
Author(s)
Tsukada, K., Inui, D., Kato, H., Maki, D., and Kitoh, T
Organizer
27th Federation of Asian Pharmaceutical Associations Congress, Philippine International Convention Center, Manila, Philippines
Related Report
Int'l Joint Research
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[Presentation] THE FIRST NATIONWIDE CLINICAL STUDY FOR THE FIRST RELAPSED ACUTE LYMPHOBLASTIC LEUKEMIA IN JAPANESE CHILDREN: THE JPLSG-ALL-R08.2018
Author(s)
C. Ogawa, H. U., M. Nishi, J. Yamanaka, S. Mochizuki, T. Nishikawa, H. Toyoda, A. Iguchi, K. Koh, S. Ota, T. Kitoh, K. Okada, T. Asano, T. Deguchi, N. Kiyokawa, T. Hori, Y. Komada, A. Moriya Saito, T. Watanabe, H. Goto.
Organizer
The 50th Congress of the International Society of Paediatric Oncology (SIOP), Kyoto
Related Report
Int'l Joint Research
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[Presentation] CHANGE IN EXPERT CONSENSUS BASED ON AVAILABILITY OF ADDITIONAL LABORATORY DATA OVER THE COURSE OF MAS:2016
Author(s)
Sergio Davi, Francesca Minoia, AnnaCarin Horne, Toshiyuki Kitoh, Raju Khubchandani, Norman T Ilowite, Jan-Inge Henter, Alexei A Grom, Fabrizio De Benedett, Alberto Martini, Nicolino Ruperto, Randy Q Cron, Angelo Ravelli
Organizer
23rd European Paediatric Rheumatology Congress
Place of Presentation
Genova, Italy
Year and Date
2016-09-28
Related Report
Int'l Joint Research
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