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A new approach for the elucidation of multiple superantigens related to the trigger of Kawasaki disease

Research Project

Project/Area Number 16K10072
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionWakayama Medical University

Principal Investigator

Suzuki Hiroyuki  和歌山県立医科大学, 医学部, 教授 (80196865)

Co-Investigator(Kenkyū-buntansha) 武内 崇  和歌山県立医科大学, 医学部, 講師 (10246522)
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) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords川崎病 / スーパー抗原 / 遺伝子水平伝播
Outline of Final Research Achievements

We performed bacterial cultures from throat samples in 130 patients with KD on admission using BHI liquid solution. After overnight incubation, total DNA were extracted from the culture solution. Then, we examined gene fragments of 4 superantigens (streptoccocus pyrogenic exotoxin-A, SPE-C, SPE-G, SPE-J) derived from Streptococcus pyogenes. The numbers of patients showing positive PCR reactions to SPE-A, SPE-C, SPE-G, SPE-J were eight, fourteen, thirty-two, five, respectively. We scattered the culture solution with PCR positive reaction to culture dishes, and then we screened each colony if it harbored SAg gene fragments or not. After these screening, we found a bacterial colony harboring SPE-G gene fragment. In addition, it was identified as streptococcus X by analysis of 16S rRNA gene.

Academic Significance and Societal Importance of the Research Achievements

川﨑病による心後遺症は、今や、後天性心疾患の中で最も頻度の高い疾患となっている。従って、川﨑病の原因を解明し、その予防法を確立することは、小児科医療に従事する者にとって喫緊の課題である。A群レンサ球菌(GAS)が本来保持するとされるスーパー抗原(streptoccocus pyrogenic exotoxin G:SPE-G)を他のレンサ球菌Xが保持しているという今回の研究成果は、SPE-Gの遺伝子がレンサ球菌間で水平伝播していることを示唆するものであり、細菌学的にも、また川﨑病原因解明の観点からも学術的意義は大きく、さらに、川﨑病発症予防への道の可能性を開くものであり社会的意義も高い。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (30 results)

All 2019 2018 2017 2016

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (21 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Efficacy of primary treatment with immunoglobulin plus ciclosporin for prevention of coronary artery abnormalities in patients with Kawasaki disease predicted to be at increased risk of non-response to intravenous immunoglobulin (KAICA): a randomised controlled, open-label, blinded-endpoints, phase 3 trial2019

    • Author(s)
      Hamada H, Suzuki H, Onouchi Y, Ebata R, Terai M, Fuse S, Okajima Y, Kurotobi S, Hirai K, Soga T, Ishiguchi Y, et al.
    • Journal Title

      Lancet.

      Volume: 393(10176): Issue: 10176 Pages: 1128-1137

    • DOI

      10.1016/s0140-6736(18)32003-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Investigation of novel variations of ORAI1 gene and their association with Kawasaki disease2019

    • Author(s)
      Thiha Kyaw、Japan Kawasaki Disease Genome Consortium、Mashimo Yoichi、Suzuki Hiroyuki、Hamada Hiromichi、Hata Akira、Hara Toshiro、Tanaka Toshihiro、Ito Kaoru、Onouchi Yoshihiro、Ikeda K, Kosuda T, Hashimoto K,
    • Journal Title

      Journal of Human Genetics

      Volume: 64 Issue: 6 Pages: 511-519

    • DOI

      10.1038/s10038-019-0588-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of SAMD9L as a susceptibility locus for intravenous immunoglobulin resistance in Kawasaki disease by genome-wide association analysis.2019

    • Author(s)
      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.
    • Journal Title

      Pharmacogenomics J.

      Volume: 印刷中 Issue: 1 Pages: 80-86

    • DOI

      10.1038/s41397-019-0085-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Patient Age and the Seasonal Pattern of Onset of Kawasaki's Disease.2018

    • Author(s)
      Kitano N, Suzuki H, Takeuchi T.
    • Journal Title

      N Engl J Med.

      Volume: 378 Issue: 21 Pages: 2048-2049

    • DOI

      10.1056/nejmc1804312

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nationwide Survey of Patients With Giant Coronary Aneurysm Secondary to Kawasaki Disease 1999–2010 in Japan2018

    • 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
    • Related Report
      2017 Research-status Report
    • 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

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Variations in ORAI1 Gene Associated with Kawasaki Disease2016

    • Author(s)
      Onouchi Y, Fukazawa R, Yamamura K, Suzuki H, Kakimoto N, Suenaga T, et al.
    • Journal Title

      PloS One

      Volume: 11 Issue: 1 Pages: e0145486-e0145486

    • DOI

      10.1371/journal.pone.0145486

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 川崎病冠動脈病変の疑いが契機となり発見された右冠動脈右室瘻の1例2016

    • Author(s)
      2.垣本信幸、末永智浩、武内崇、鈴木啓之、渋田昌一、立花伸也、竹腰信人、横山宏司、原茂登、吉田晃
    • Journal Title

      Prog Med

      Volume: 36 Pages: 892-895

    • Related Report
      2016 Research-status Report
  • [Journal Article] 川崎病の過去・現在・未来2016

    • Author(s)
      鈴木啓之
    • Journal Title

      和歌山医学

      Volume: 67 Pages: 122-129

    • NAID

      40021060615

    • Related Report
      2016 Research-status Report
  • [Presentation] Relationship of three gene polymorphisms related to Ca2+ /NFAT-pathway with clinical characteristics in the acute phase of Kawasaki disease.2018

    • Author(s)
      Suzuki T, Kakimoto N, Onouchi Y, Suenaga T, Takeuchi T, Tachibana S, Takekoshi N, Shibuta S, Suzuki H.:
    • Organizer
      The 12th International Kawasaki Disease Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Are the serum levels of immunoglobulin G in patients with Kawasaki disease lower than those in other children?2018

    • Author(s)
      Suenaga T, Suzuki T, Kakimoto N, Takeuchi T, Suzuki H:
    • Organizer
      The 12th International Kawasaki Disease Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The interaction between patients’ age and sex in the development of coronary artery lesions attributable with Kawasaki disease in Japan2018

    • Author(s)
      Kitano N, Takeuchi T, Suenaga T, Kakimoto N, Shibuta S, Suzuki T, Tachibana S, Takekoshi N, Suzuki H
    • Organizer
      The 12th International Kawasaki Disease Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] What role do the vasa vasorum play in the sequelae of coronary arterial lesions in Kawasaki disease?2018

    • Author(s)
      Kakimoto N, Takeuchi T, Taruya A, Ino Y, Tanaka A, Kubo T, Suzuki T, Suenaga T, Akasaka T, Suzuki H.
    • Organizer
      The 12th International Kawasaki Disease Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 当院における川崎病冠動脈病変の評価について~厚生省川崎病研究班基準(1984)とZ-scoreとの後方視的比較検討~2018

    • Author(s)
      鈴木崇之、垣本信幸、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42回近畿川崎病研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 川崎病遠隔期冠動脈病変の修復過程にVasa Vasorumはどのような役割を果たしているか?2018

    • 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、渋田昌一、赤阪隆史、鈴木啓之:
    • Organizer
      第54回小児循環器学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 和歌山医大における川崎病冠動脈病変の評価について2018

    • Author(s)
      木崇之、垣本信幸、竹腰信人、立花伸也、渋田昌一、末永智浩、武内 崇、鈴木啓之
    • Organizer
      和歌山医大における川崎病冠動脈病変の評価について
    • Related Report
      2018 Annual Research Report
  • [Presentation] 発症後2ヶ月時に冠動脈造影および光干渉断層像検査を 施行できた1例2018

    • Author(s)
      土橋智弥、垣本信幸、武内 崇、樽谷 玲、猪野 靖、田中 篤、久保隆史、末永智浩、 渋田昌一、赤阪隆史、鈴木啓之
    • Organizer
      第38回日本川崎病学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 川崎病罹患者の年齢と発症の季節性について2018

    • Author(s)
      北野尚美、武内 崇、末永智浩、垣本信幸、立花伸也、竹腰信人、鈴木崇之、土橋智弥、 澁田昌一、鈴木啓之、和歌山川崎病研究会:
    • Organizer
      第38回日本川崎病学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 川崎病診断基準を満たした 35歳男性の1例2017

    • Author(s)
      末永智浩、立花伸也、垣本信幸、武内崇、鈴木啓之、村上大地、杉田 玄、保富宗城、 渋田昌一、竹腰信人
    • Organizer
      第41回近畿川崎病研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 主要症状が2-3/6のために川崎病と診断されず、冠動脈病変を形成した3例の検討2017

    • Author(s)
      立花伸也、鈴木啓之、武内崇、 末永智浩、垣本信幸、渋田昌一
    • Organizer
      第30回近畿小児科学会
    • Related Report
      2017 Research-status Report
  • [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
    • Related Report
      2017 Research-status Report
  • [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37回日本川崎病学術集会
    • Related Report
      2017 Research-status Report
  • [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
    • Related Report
      2017 Research-status Report
  • [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
    • Related Report
      2017 Research-status Report
  • [Presentation] 和歌山県下における川崎病の疫学的特徴と治療の変遷に伴う冠動脈病変発生率の推移2017

    • Author(s)
      北野尚美,武内 崇,末永智浩,垣本信幸,鈴木崇之,立花伸也,澁田昌一,山野貴司,赤阪隆史,鈴木啓之, 和歌山川崎病研究会
    • Organizer
      第37回日本川崎病学術集会
    • Related Report
      2017 Research-status Report
  • [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
    • Related Report
      2017 Research-status Report
  • [Presentation] 光緩衝断層法(OCT)を用いた遠隔期の冠動脈病変の評価2016

    • Author(s)
      5.垣本信幸、武内崇、猪野靖、久保隆史、末永智浩、立花伸也、渋田昌一、赤坂隆史、鈴木啓之
    • Organizer
      第36回日本川崎病学会・学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-09-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 川崎病発症時の血清IgG値は年齢相当よりも低い?2016

    • Author(s)
      6.末永智浩、鈴木啓之、立花伸也、垣本信幸、武内崇、渋田昌一、竹腰信人
    • Organizer
      第36回日本川崎病学会・学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-09-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 川崎病発症と冠動脈障害発生に対する罹患年齢のリスクは性で層化した評価が必要2016

    • Author(s)
      8.北野尚美、中 暁洋、武内 崇、末永智浩、垣本信幸、渋田昌一、上野雅巳、鈴木啓之、和歌山川崎病研究会グループ
    • Organizer
      第36回日本川崎病学会・学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-09-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 主要症状が2-3/6のために川崎病と診断されず、冠動脈瘤を形成した3例の検討2016

    • Author(s)
      7.立花 伸也、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36回日本川崎病学会・学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-09-30
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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