New molecular genetic examination of the mechanism of cyclosporin A in the initial treatment for kawasaki disease

• Project/Area Number: 15K09696
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Wakayama Medical University
• Principal Investigator: Takeuchi Takashi 和歌山県立医科大学, 医学部, 講師 (10246522)
• Co-Investigator(Kenkyū-buntansha): 鈴木 啓之 和歌山県立医科大学, 医学部, 教授 (80196865) ; 末永 智浩 和歌山県立医科大学, 医学部, 助教 (70433365) ; 垣本 信幸 和歌山県立医科大学, 医学部, 助教 (90614412)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 川崎病 / シクロスポリンA / 細胞内シグナル伝達 / 炎症性サイトカイン

Outline of Final Research Achievements

We started a multicenter physician-led trial to compare the utility of IVIG plus cyclosporin A(CsA) combination therapy with the IVIG monotherapy as initial treatment in severe Kawasaki disease(KD). It is a purpose that this study elucidates mechanism of action of IVIG and CsA using a blood sample before and after the initial treatment with CsA for severe KD. Thirteen cases were enrolled in this trial in our hospital. We conducted RNA extraction and serum isolation from the blood sample of these patients and prepared for the measurement of the gene expression level. In total, we measured inflammatory cytokine (sIL-2R,IL2,4,6,10,TNF etc.) for 11 cases 29 points, including IVIG effective cases, resistant cases, IVIG+CsA effective cases, and resistant cases.

Research Products

• [Journal Article] Nationwide Survey of Patients With Giant Coronary Aneurysm Secondary to Kawasaki Disease 1999–2010 in Japan (2018)
  • Author(s): Fukazawa R, Kobayashi T, Mikami M, Saji T, Hamaoka K, Kato H, Suzuki H, Tsuda E, Ayusawa M, Miura M, Ebata R, Kobayashi T, Yashiro M, Ogawa S.
  • Journal Title: Circulation Journal Volume: 82 Issue: 1 Pages: 239-246
  • DOI: 10.1253/circj.CJ-17-0433
  • NAID: 130006281999
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] Male-specific association of the FCGR2A His167Arg polymorphism with Kawasaki disease. (2017)
  • Author(s): Kwon YC, Kim JJ, Yun SW, Yu JJ, Yoon KL, Lee KY, Kil HR, Kim GB, Han MK, Song MS, Lee HD, Ha KS, Sohn S, Ebata R, Hamada H, Suzuki H, Ito K, Onouchi Y, Hong YM, Jang GY, Lee JK; Korean Kawasaki Disease Genetics Consortium.
  • Journal Title: PLoS One Volume: 12 Issue: 9 Pages: e0184248-e0184248
  • DOI: 10.1371/journal.pone.0184248
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Variations in ORAI1 Gene Associated with Kawasaki Disease (2016)
  • Author(s): Onouchi Y, Fukazawa R, Yamamura K, Suzuki H, Kakimoto N, Suenaga T, Takeuchi T, Hamada H, Honda T, Yasukawa K, Terai M, Ebata R, Higashi K, Saji T, Kemmotsu Y, Takatsuki S, Ouchi K, Kishi F, Yoshikawa T, Nagai T
  • Journal Title: PLoS One Volume: -
  • Peer Reviewed / Open Access
• [Presentation] What role do the vasa vasorum play in the sequelae of coronary arterial lesions in Kawasaki disease? (2018)
  • Author(s): Nobuyuki Kakimoto, Takashi Takeuchi, Akira Taruya, Yasushi Ino, Atsushi Tanaka, Takashi Kubo, Tomohiro Suenaga, Shoichi Shibuta, Takashi Akasaka, Hiroyuki Suzuki
  • Organizer: The 82nd Annual Scientific Meeting of the Japanese Circulation Society
  • Invited
• [Presentation] Ca2+/NFAT 経路関連３遺伝子多型から見た川崎病の急性期臨床像 (2017)
  • Author(s): 鈴木崇之、垣本信幸、尾内善広、立花伸也、竹腰信人、渋田昌一、末永智浩、武内 崇、鈴木啓之
  • Organizer: 第53回日本小児循環器学会
• [Presentation] 光緩衝断層法（OCT）を用いた川崎病遠隔期冠動脈病変におけるVasa Vasorumの検討 (2017)
  • Author(s): 垣本信幸、武内崇、樽谷玲、猪野靖、田中篤、久保隆史、末永智浩、立花伸也、渋田昌一、赤阪隆史、鈴木啓之
  • Organizer: 第53回日本小児循環器学会
• [Presentation] 川崎病冠動脈瘤に合併した新鮮瘤内血栓に対するtissue-type plasminogen activator(t-PA)による血栓溶解療法の有用性 (2017)
  • Author(s): 立花伸也、鈴木崇之、垣本信幸、末永智浩、武内崇、鈴木啓之、澁田昌一、竹腰信人
  • Organizer: 第37回日本川崎病学術集会
• [Presentation] 川崎病遠隔期冠動脈病変におけるVasa Vasorumの分析 (2017)
  • Author(s): 垣本信幸、武内 崇、樽谷 玲、猪野 靖、田中 篤、久保隆史、鈴木崇之、末永智浩、竹腰信人、立花伸也、渋田昌一、赤坂隆史、鈴木啓之
  • Organizer: 第37回日本川崎病学術集会
• [Presentation] 川崎病治療後における血清免疫グロブリン値の長期的推移 (2017)
  • Author(s): 末永智浩、鈴木啓之、鈴木崇之、垣本信幸、武内崇、渋田昌一、立花伸也、竹腰信人
  • Organizer: 第37回日本川崎病学術集会