Biomarker development in Kawasaki disease and new treatment strategies for refractory cases

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09697
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Jichi Medical University
• Principal Investigator: MINAMI TAKAOMI 自治医科大学, 医学部, 非常勤講師 (60423951)
• Co-Investigator(Kenkyū-buntansha): 佐藤 智幸 自治医科大学, 医学部, 講師 (20567995) ; 森本 哲 自治医科大学, 医学部, 教授 (30326227)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 川崎病 / 免疫グロブリン / シクロスポリン持続静注療法

Outline of Final Research Achievements

The involvement of platelet activating factor (PAF) has been reported in refractory cases of Kawasaki disease (patients who are resistant to intravenous immunoglobulin [IVIG]). Continuous intravenous injection of cyclosporin (CsA), which inhibits the transcription factor NFAT in the inflammatory response pathway of PAF at a dose of 3 mg/kg/day was administered in 50 patients with IVIG resistance. Consequently, symptoms subsided within 7 days in all patients (72% of all patients within 24 hours). The proportion of patients with coronary artery aneurysm was very small (only 1 [2%] patient with middle aneurysm) compared to the previous reported 10.1% (after 30 days of disease). In addition, levels of soluble IL-2 receptor, which is a marker of T cell activation, were also significantly decreased before and after CsA administration, suggesting the involvement of T-cell activation in refractory cases of Kawasaki disease.

Free Research Field

小児循環器学、川崎病

Academic Significance and Societal Importance of the Research Achievements

川崎病は、乳幼児に特に多い全身性血管炎で、現在も原因不明である。研究開始当時、約5％に冠動脈瘤を残していた。免疫グロブリン療法（IVIG）に反応しない不応例は、冠動脈瘤のリスクが約8－10倍で、その対応が課題であった。本研究は、学術的には、川崎病IVIG不応例の免疫学的機序の一端を明らかにするとともに、シクロスポリン持続静注療法という治療法の選択肢を示した点で、社会的にも意義があると考えられる。