Establishment of a prediction system of relapse in Kawasaki disease based on cytokine response.

• Project/Area Number: 20K16937
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: St. Luke's International University
• Principal Investigator: ONO Rintaro 聖路加国際大学, 聖路加国際病院, 医員 (80841197)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: サイトカイン / 川崎病 / 免疫

Outline of Research at the Start

川崎病は小児に生じる原因不明の発熱性疾患である。高リスク患者の抽出と適切な介入により冠動脈瘤の形成を予防するストラテジーの開発は重要な課題である。
本研究では、治療前後の川崎病患者をはじめとした様々な小児炎症性疾患患者サンプルを用いて、サイトカイン解析と、免疫細胞サブセット解析を行い、それらを臨床所見、検査データと統合することで、疾患の病態理解の向上ならびに、治療不応・再燃リスクの高い患者を早期抽出し、適切な介入を可能とすることを目指す。

Outline of Final Research Achievements

Cytokine profiling was performed on pre- and post-treatment samples in 63 patients with Kawasaki disease. In some cases, immune-profiling was also performed using mass cytometry. For comparison, these analyses were also performed in hypercytokine-associated other pediatric diseases such as hemophagocytic lymphohistiocytosis. This study revealed that even patients with Kawasaki disease exhibit different cytokine patterns and immune cell subset patterns. Further analysis is warranted in larger cohort of Kawasaki disease and other hypercytokine diseases.

Academic Significance and Societal Importance of the Research Achievements

川崎病患者において、共通して上昇するサイトカインよび患者、治療経過ごとに異なるサイトカインのパターンを明らかにした。本研究の成果を応用し、将来的にサイトカイン解析から再発・難治例を予測し、個々の患者にとって最適と考えられる治療を提案できる可能性がある。

Research Products

• [Journal Article] Novel STAT1 Variants in Japanese Patients with Isolated Mendelian Susceptibility to Mycobacterial Diseases (2022)
  • Author(s): Ono R, Tsumura M, Shima S, Matsuda Y, Gotoh K, Miyata Y, Yoto Y, Tomomasa D, Utsumi T, Ohnishi H, Kato Z, Ishiwada N, Ishikawa A, Wada T, Uhara H, Nishikomori R, Hasegawa D, Okada S, Kanegane H.
  • Journal Title: Journal of Clinical Immunology Volume: 43 Issue: 2 Pages: 466-478
  • DOI: 10.1007/s10875-022-01396-1
  • Peer Reviewed / Open Access
• [Journal Article] Prevalence and characteristics of Kawasaki disease before and during the COVID-19 pandemic (2021)
  • Author(s): Ono Rintaro、Hasegawa Daisuke
  • Journal Title: World Journal of Pediatrics Volume: 17 Issue: 2 Pages: 215-217
  • DOI: 10.1007/s12519-021-00412-5
  • Peer Reviewed
• [Journal Article] Targeting critical kinases and anti-apoptotic molecules overcomes steroid resistance in MLL-rearranged leukaemia (2021)
  • Author(s): de Groot AP.、Saito Y、Kawakami E、Hashimoto M、Aoki Y、Ono R、Ogahara I、Fujiki S、Kaneko A、Sato K、Kajita H、Watanabe T、Takagi M、Tomizawa D、Koh K、Eguchi M、Ishii Ei、Ohara O、Shultz LD.、Mizutani S、Ishikawa F
  • Journal Title: EBioMedicine Volume: 64 Pages: 103235-103235
  • DOI: 10.1016/j.ebiom.2021.103235
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ruxolitinib for hematopoietic cell transplantation-associated hemophagocytic lymphohistiocytosis (2020)
  • Author(s): Ono Rintaro、Ashiarai Miho、Hirabayashi Shinsuke、Mizuki Kazuyoshi、Hosoya Yosuke、Yoshihara Hiroki、Ohtake Junya、Mori Shinichiro、Manabe Atsushi、Hasegawa Daisuke
  • Journal Title: International Journal of Hematology Volume: 113 Issue: 2 Pages: 297-301
  • DOI: 10.1007/s12185-020-02999-3
  • Peer Reviewed