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Study of the mechanism and therapeutic biomarkers for sublingual immunotherapy by using the EXiLE method

Research Project

Project/Area Number 16H05483
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionNational Institute of Health Sciences

Principal Investigator

Nakamura Ryosuke  国立医薬品食品衛生研究所, 医薬安全科学部, 室長 (50333357)

Co-Investigator(Kenkyū-buntansha) 岡本 美孝  千葉大学, 大学院医学研究院, 教授 (40169157)
秋山 晴代  帝京平成大学, 薬学部, 講師 (50420229)
岡本 好海 (内田)  国立医薬品食品衛生研究所, 医薬安全科学部, 任期付研究員 (40716792)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2016: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywordsアレルゲン舌下免疫療法 / EXiLE法 / IgE / IgG / バイオマーカー / ルシフェラーゼ / 舌下免疫療法 / EXiLE / アレルギー
Outline of Final Research Achievements

In this study we aimed to explore a biomarker that can predict the clinical response to sublingual immunotherapy (SLIT). Patients allergic to Japanese cedar pollen (JCP) were administered with JCP SLIT for more than 2 seasons. The severity of symptoms of pollinosis was represented by an averaged total nasal symptoms medication score (TNSMS) in the peak season. Crosslinking ability of patients’ serum IgE on the addition of JCP extract was determined by our original cell-based allergy test; IgE crosslinking-induced luciferase expression (EXiLE) method. When the reporter cells were sensitized with patients’ sera collected before starting SLIT, JCP-induced EXiLE response of more than 2.0 fold was an effective threshold to distinguish good and poor responders in SLIT judged by TNSMS diference (P<0.001). These results suggest that specific IgE crosslinking ability at SLIT entry would be a good biomarker candidate to predict the clinical response to SLIT.

Academic Significance and Societal Importance of the Research Achievements

近年、舌下免疫療法(SLIT)という画期的なアレルギーの治療法が開発された。しかしこの治療法は長期(数年)にわたって実施する必要があるため、治療開始時にSLITがよく効く患者とそうでない患者を見分ける手法の開発が求められていた。我々が近年開発した「EXiLE法」という手法を用いると、治療開始前にEXiLE法の応答性が高い患者ほど、SLITがよく効いていることが分かった。この方法により、SLITがよく効く患者を事前に見分けてから長期にわたるSLITを実施するという個別化医療が実現できるかもしれない。

Report

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

    (24 results)

All 2019 2018 2017 2016

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (14 results) (of which Int'l Joint Research: 3 results) Book (2 results)

  • [Journal Article] An analysis of factors related to the effect of sublingual immunotherapy on Japanese cedar pollen induced allergic rhinitis2018

    • Author(s)
      Yonekura S, Okamoto Y, Sakurai D, Okubo K, Gotoh M, Kaneko S, Konno A.
    • Journal Title

      Allergology International

      Volume: 67 Issue: 2 Pages: 201-208

    • DOI

      10.1016/j.alit.2017.07.005

    • NAID

      130006721780

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathogenicity of memory Th2 cells is linked to stage of allergic rhinitis2018

    • Author(s)
      Iinuma T.、Okamoto Y.、Morimoto Y.、Arai T.、Sakurai T.、Yonekura S.、Sakurai D.、Hirahara K.、Nakayama T.
    • Journal Title

      Allergy

      Volume: 73 Issue: 2 Pages: 479-489

    • DOI

      10.1111/all.13295

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunosuppressive property of submandibular lymph nodes in patients with head and neck tumors: differential distribution of regulatory T cells2018

    • Author(s)
      Sakurai D, Uchida R, Ihara F, Kunii N, Nakagawa T, Chazono H, Hanazawa T, Motohashi S, Okamoto Y
    • Journal Title

      BMC Research Notes

      Volume: 11 Issue: 1 Pages: 479-479

    • DOI

      10.1186/s13104-018-3587-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of specifically reduced Th2 cell subsets in allergic rhinitis patients after sublingual immunotherapy2018

    • Author(s)
      1.Ihara F, Saurai D, Yonekura S, Iinuma T, Matsuura A, Morimoto Y, Arai T, Suzuki S, Katayama K, Nakayama T, Okamoto Y
    • Journal Title

      Allergy

      Volume: 73 Issue: 9 Pages: 1823-1832

    • DOI

      10.1111/all.13436

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] House dust mite sublingual tablet is effective and safe in patients with allergic rhinitis.2017

    • Author(s)
      Okamoto Y, Fujieda S, Okano M, Yoshida Y, Kakudo S, Masuyama K.
    • Journal Title

      Allergy

      Volume: 72 Issue: 3 Pages: 435-443

    • DOI

      10.1111/all.12996

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] アレルギー試験法と標準化免疫療法用アレルゲン2017

    • Author(s)
      中村亮介
    • Journal Title

      医薬品医療機器レギュラトリーサイエンス

      Volume: 48 Pages: 525-532

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Different Results of IgE Binding- and Crosslinking-Based Allergy Tests Caused by Allergen Immobilization2016

    • Author(s)
      Okamoto-Uchida Y, Nakamura R, Matsuzawa Y, Soma M, Kawakami H, Ishii-Watabe A, Nishimaki-Mogami T, Teshima R, Saito Y.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 39 Issue: 10 Pages: 1662-1666

    • DOI

      10.1248/bpb.b16-00389

    • NAID

      130005598496

    • ISSN
      0918-6158, 1347-5215
    • URL

      https://pure.teikyo.jp/en/publications/6abb146a-da62-491b-b3e9-a4e794d6f491

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Th2 cells in health and disease.2016

    • Author(s)
      Nakayama T, Hirahara K, Onodera A, Endo Y, Hosokawa H, Shinoda K, Tumes DJ, Okamoto Y.
    • Journal Title

      Annu Rev Immunol.

      Volume: 35 Issue: 1 Pages: 53-84

    • DOI

      10.1146/annurev-immunol-051116-052350

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] スギ花粉症の舌下免疫療法の奏効性は血清中IgEの架橋能と相関する2019

    • Author(s)
      中村亮介, 秋山晴代, 櫻井大樹, 松澤由美子, 斎藤嘉朗, 岡本美孝
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] セツキシマブによる牛肉アレルギー患者血清中IgE架橋活性の解析2018

    • Author(s)
      中村亮介, 岡本(内田)好海, 千貫祐子, 斎藤嘉朗, 森田栄伸
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 舌下免疫療法実施時における血清中中和抗体活性のin vitro評価法の開発2018

    • Author(s)
      秋山晴代, 中村亮介, 櫻井大樹, 平野吉彬, 根来孝治, 岡本美孝
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 試料調製条件が血漿プロテオーム解析に及ぼす影響について2018

    • Author(s)
      中村亮介, 荒川憲昭, 前川京子, 斎藤嘉朗
    • Organizer
      第45回日本毒性学会学術年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Crosslinking ability of the serum IgE correlates to the effectiveness of allergen immunotherapy for Japanese cedar pollen2018

    • Author(s)
      Nakamura R, Akiyama H, Sakurai D, Matsuzawa Y, Saito Y, Okamoto Y
    • Organizer
      WISC 2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] 経口免疫寛容誘導時における減感作状態のEXiLE法を用いた評価2018

    • Author(s)
      秋山晴代、西村光平、中村亮介、堀雅之、甲斐茂美、松藤寛、根来孝治、宮澤眞紀、松原康策
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 各種大豆加工食品のアレルゲン性評価法II ~EXiLE法を用いた大豆アレルゲンの加工に伴う抗原性の変化の解析~2017

    • Author(s)
      秋山晴代, 渡邊裕子, 政岡智佳, 中村亮介, 田中裕, 甲斐茂美, 栗原和幸, 宮澤眞紀
    • Organizer
      第65回日本アレルギー学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2017-06-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] 培養細胞を用いたアレルゲン性評価法の開発2017

    • Author(s)
      大岩亮介, 嶋倉邦嘉, 中村亮介, 黒瀬光一
    • Organizer
      平成 29年度日本水産学会春季大会
    • Place of Presentation
      東京
    • Year and Date
      2017-03-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] 酸加水分解コムギの脱アミド化エピトープを特異的に認識するモノクローナル抗体を用いた抗原性の解析2017

    • Author(s)
      酒井信夫, 田原麻衣子, 中村里香, 中村亮介, 佐々木和実, 西嶋桂子, 安宅花子, Olivier Tranquet, Sandra Denery, 佐藤奈由, 中村政志, 松永佳世子, 手島玲子, 安達玲子, 五十嵐良明
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Different responses of basophils to allergen between sensitized-asymptomatic subjects and patients with allergic rhinitis.2017

    • Author(s)
      Okamoto Y, Yonekura S, Arai T, Sakurai D.
    • Organizer
      AAAAI2017
    • Place of Presentation
      アトランタ
    • Year and Date
      2017-03-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] EXiLE法によるコチニールアレルギー患者IgEの抗原性解析2017

    • Author(s)
      為広紀正, 安達玲子, 中村政志, 竹尾直子, 山口正雄, 中村亮介, 永井晶代, 矢上晶子, 松永佳世子, 近藤一成
    • Organizer
      第66回日本アレルギー学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] EXiLE法を用いた経口免疫療法実施時における減感作状態の評価法の検討(第2報)2017

    • Author(s)
      秋山晴代、鈴木麻希、中村亮介、田中裕、甲斐茂美、栗原和幸、宮澤眞紀
    • Organizer
      第66回日本アレルギー学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Efficacy and safety of S-524101 in mono-sensitized and poly-sensitized patients with allergic rhinitis in Japan Phase 2/3 study2016

    • Author(s)
      Okamoto Y, Fujieda S, Masuyaka K, Okano M, Kakudo M.
    • Organizer
      EAACI2016
    • Place of Presentation
      ウィーン
    • Year and Date
      2016-06-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Current concepts on immune mechanisms of sublingual immunotherapy2016

    • Author(s)
      Okamoto Y.
    • Organizer
      18th Asian Research Symposium of Rhinology
    • Place of Presentation
      クアラルンプール
    • Year and Date
      2016-05-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Book] Food Allergy, Methods and Protocols, Part II2017

    • Author(s)
      Ali-Ali E, Nakamura R, Falcone FH.
    • Total Pages
      299
    • Publisher
      Springer Nature
    • Related Report
      2016 Annual Research Report
  • [Book] アレルギー疾患のすべて2016

    • Author(s)
      岡本美孝
    • Total Pages
      367
    • Publisher
      日本医師会
    • Related Report
      2016 Annual Research Report

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

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