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Pathophysiological elucidation of urticaria targeting basophils and its application to drug discovery

Research Project

Project/Area Number 20K08651
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionOsaka Medical and Pharmaceutical University (2022)
Kobe University (2020-2021)

Principal Investigator

Fukunaga Atsushi  大阪医科薬科大学, 医学部, 准教授 (10467649)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords慢性蕁麻疹 / 好塩基球 / 慢性特発性蕁麻疹 / 慢性刺激誘発性蕁麻疹 / IgE / FcεRI / オマリズマブ / 刺激誘発型蕁麻疹 / 反応性 / 蕁麻疹 / アナフィラキシー / 病態解明
Outline of Research at the Start

蕁麻疹は非常にありふれた疾患であるが、根本的治療法が確立されていない。食物アレルギーのように原因が判明すれば原因の除去回避、原因が不明な慢性蕁麻疹では薬物治療が治療のベースとなる。薬物治療を行っても症状が消失しない症例や病型も多く、強いかゆみのために日常生活に大きな問題が生じる。ありふれた疾患でありながら蕁麻疹を発症するメカニズムについては不明点が多く、メカニズムの解明を進めることは新たな治療法の確立のために重要課題である。今回の研究では、蕁麻疹の発症初期への関与が推測されている好塩基球の役割に着目し、蕁麻疹全体の病態の解明と新しい治療法の開発の基盤とする。

Outline of Final Research Achievements

Urticaria is classified into spontaneous and inducible types, and there are many intractable cases and disease types in which antihistamines do not relieve symptoms, and no fundamental treatment has been established. Cutaneous mast cells are involved in the pathogenesis of urticaria in urticaria, but the overall picture has not been elucidated. This study focused on the role of basophils in the pathogenesis of chronic spontaneous urticaria, which is the most common disease type, and chronic inducible urticaria, which is resistant to various treatments.
In chronic spontaneous urticaria, basophils with abnormal IgE-FcεRI signals are involved in pathogenesis, whereas in chronic inducible urticaria, basophil function is normal and may be less involved in pathogenesis. We believe that this study will contribute to the establishment of disease-type-specific treatments for urticaria.

Academic Significance and Societal Importance of the Research Achievements

蕁麻疹は一生涯で多くの人が罹患する痒みが強くQoLを著しく害する病気であるが、本研究においては蕁麻疹の中でも長く続く病型である慢性蕁麻疹に焦点を当て研究を行った。慢性蕁麻疹は明らかな誘因がなく続く慢性特発性蕁麻疹と特定の刺激で誘発される慢性刺激誘発性蕁麻疹に分類されどちらのタイプでも抗ヒスタミン剤の効果が不十分なことが多い。
本研究結果は慢性特発性蕁麻疹では痒みの主成分であるヒスタミンを遊離する細胞で通常血管内に存在する好塩基球が病態の形成に関わる一方で慢性刺激誘発性蕁麻疹では病態の形成に深く関わらないことを証明した。本研究は蕁麻疹の病型に特異的な治療法の確立に寄与する研究であると考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (34 results)

All 2022 2021 2020

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 6 results) Presentation (19 results) (of which Int'l Joint Research: 7 results,  Invited: 12 results) Book (1 results)

  • [Journal Article] Current status of the satisfaction levels of adult patients receiving drugs for atopic dermatitis and chronic urticaria2022

    • Author(s)
      Kaneko S, Nakahara T, Sumikawa Y, Fukunaga A, Masuda K, Kakamu T, Morita E.
    • Journal Title

      Journal of Cutaneous Immunology and Allergy.

      Volume: 5 Pages: 4-11

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of physicians’ clinical experience and workplace on patients’ care of urticaria in Japan: A sub-analysis of a nation-wide cross-sectional web questionnaire survey.2022

    • Author(s)
      Takahagi S, Kamegashira A, Inomata N, Fukunaga A, Nakahara T, Hayama K, Hide M.
    • Journal Title

      Journal of Cutaneous Immunology and Allergy.

      Volume: 5 Pages: 106-108

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lower efficacy of omalizumab in older adults with chronic spontaneous urticaria2022

    • Author(s)
      Kitao Rikuma、Oda Yoshiko、Washio Ken、Tai Yukimasa、Ono Ryusuke、Nishigori Chikako、Fukunaga Atsushi
    • Journal Title

      The Journal of Dermatology

      Volume: - Issue: 7 Pages: 729-731

    • DOI

      10.1111/1346-8138.16370

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IgE receptor responsiveness of basophils in chronic inducible urticaria.2022

    • Author(s)
      Mizuno M, Oda Y, Imamura S, Washio K, Fukumoto T, Fukunaga A.
    • Journal Title

      Front Immunol.

      Volume: 13 Pages: 995596-995596

    • DOI

      10.3389/fimmu.2022.995596

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy of additional treatment for chronic spontaneous urticaria refractory to treatment ? A single‐center retrospective real‐world study2021

    • Author(s)
      Ohata Marie、Oda Yoshiko、Washio Ken、Fukunaga Atsushi、Nishigori Chikako
    • Journal Title

      The Journal of Dermatology

      Volume: 49 Issue: 1

    • DOI

      10.1111/1346-8138.16183

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Case of oral mite anaphylaxis: Contamination of wheat flour by mites determined by enzyme‐linked immunosorbent assay2021

    • Author(s)
      Matsumoto Yukari、Imamura Shinya、Fukumoto Ayako、Lee Kasumi、Nishitani Nao、Oda Yoshiko、Washio Ken、Fukunaga Atsushi
    • Journal Title

      The Journal of Dermatology

      Volume: 49 Issue: 2

    • DOI

      10.1111/1346-8138.16227

    • NAID

      120007191243

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activated steady status and distinctive FcεRI-mediated responsiveness in basophils of atopic dermatitis2021

    • Author(s)
      Imamura S, Washio K, Mizuno M, Oda Y, Fukunaga A, Nishigori C.
    • Journal Title

      Allergol Int.

      Volume: 70 Issue: 3 Pages: 327-334

    • DOI

      10.1016/j.alit.2021.01.005

    • NAID

      130008064047

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.2021

    • Author(s)
      Kocaturk E, Fukunaga A, Maurer M et al.
    • Journal Title

      Allergy

      Volume: 76 Issue: 3 Pages: 816-830

    • DOI

      10.1111/all.14687

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ADVANCES IN THE TREATMENT AND ELUCIDATION OF THE PATHOPHYSIOLOGY OF CHRONIC URTICARIA2021

    • Author(s)
      Atsushi Fukunaga
    • Journal Title

      Japanese Journal of Allergology

      Volume: 70 Issue: 10 Pages: 1363-1370

    • DOI

      10.15036/arerugi.70.1363

    • NAID

      130008128877

    • ISSN
      0021-4884, 1347-7935
    • Related Report
      2021 Research-status Report
  • [Journal Article] Improved FcεRI-Mediated CD203c Basophil Responsiveness Reflects Rapid Responses to Omalizumab in Chronic Spontaneous Urticaria2021

    • Author(s)
      Oda Yoshiko、Fukunaga Atsushi、Washio Ken、Imamura Shinya、Mizuno Mayuko、Hatakeyama Mayumi、Ogura Kanako、Nishigori Chikako
    • Journal Title

      The Journal of Allergy and Clinical Immunology: In Practice

      Volume: 9 Issue: 3 Pages: 1166-1176.e8

    • DOI

      10.1016/j.jaip.2020.08.048

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of the basophil activation test to detect photoallergens in solar urticaria2020

    • Author(s)
      Oda Yoshiko、Washio Ken、Fukunaga Atsushi、Mizuno Mayuko、Hirai Hiroyuki、Imamura Shinya、Hatakeyama Mayumi、Ogura Kanako、Nishigori Chikako
    • Journal Title

      The Journal of Allergy and Clinical Immunology: In Practice

      Volume: 8 Issue: 8 Pages: 2817-2819.e1

    • DOI

      10.1016/j.jaip.2020.04.042

    • NAID

      120006897897

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] High prevalence of epilepsy in HAE with normal C1?INH2020

    • Author(s)
      Kuwahara Saki、Fukunaga Atsushi、Ohata Marie、Nakatani Shoko、Yokoyama Daisuke、Nakauchi Emi、Yoshioka Ai、Kinoshita Masako、Nishigori Chikako
    • Journal Title

      Allergology International

      Volume: 69 Issue: 4 Pages: 630-632

    • DOI

      10.1016/j.alit.2020.04.008

    • NAID

      130007926234

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A visual analogue scale for itch and pain in 23 cases of cholinergic urticaria2020

    • Author(s)
      Mizuno M.、Fukunaga A.、Washio K.、Imamura S.、Oda Y.、Nishigori C.
    • Journal Title

      Journal of the European Academy of Dermatology and Venereology

      Volume: 34 Issue: 9

    • DOI

      10.1111/jdv.16410

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Occupational respiratory allergy to lettuce in lettuce farmers2020

    • Author(s)
      Sekiya Reina、Nagano Tatsuya、Moriyama Tatsuya、Kishi Toshiyuki、Shinke Haruko、Yano Erika、Hatano Naoya、Katsurada Masahiro、Umezawa Kanoko、Katsurada Naoko、Hori Suya、Hazeki Nobuko、Fukunaga Atsushi、Yamamoto Masatsugu、Kamiryo Hiroshi、Shinohara Masakazu、Kobayashi Kazuyuki、Kotani Yoshikazu、Nishimura Yoshihiro
    • Journal Title

      Clinical & Experimental Allergy

      Volume: 50 Issue: 8 Pages: 932-941

    • DOI

      10.1111/cea.13682

    • NAID

      120006877484

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] なぜ人には蕁麻疹が必要か? 蕁麻疹関連の最新のトピックスから蕁麻疹の本質について考える2022

    • Author(s)
      福永 淳
    • Organizer
      第121回日本皮膚科学会総会(モーニングセミナー)
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Steady-state activation and suppressed responsiveness of basophils from patients with atopic dermatitis2022

    • Author(s)
      Shinya Imamura, Takeshi Fukumoto, Yoshiko Oda, Ken Washio, Mayuko Mizuno, Akiharu Kubo, Atsushi Fukunaga
    • Organizer
      2022 ESDR
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 日光蕁麻疹:病態から治療まで2022

    • Author(s)
      福永 淳
    • Organizer
      第73回日本皮膚科学会総会中部支部 シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 蕁麻疹診療ガイドラインはどこまで浸透しているか? -ガイドラインの要点の再確 認と今後に向けた治療トピックス-2022

    • Author(s)
      福永 淳
    • Organizer
      第86回日本皮膚科学会東京支部学術大会 モーニングセミナー
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] UCAREセンター/ACAREセンターの目指すところ2022

    • Author(s)
      福永 淳
    • Organizer
      第52回 日本皮膚免疫アレルギー学会学術大会 シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 新たなステージに入った遺伝性血管性浮腫(HAE)の今後の治療戦略ー長期予防薬をどう使いこなすか?ー2022

    • Author(s)
      福永 淳
    • Organizer
      第451回日本皮膚科学会北陸地方会 石川県分科会ランチョンセミナー
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 慢性蕁麻疹に対するオマリズマブの治療反応性予測因子と長期的使用実態に関する後方視的解析2021

    • Author(s)
      北尾 陸将、織田 好子 有吉 綾香 藤井 翔太郎 田井 志正 鷲尾 健 小野 竜輔 福永 淳、錦織 千佳子
    • Organizer
      第120回日本皮膚科学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] オマリズマブの安全性及び有効性を検討した特定使用成績調査2021

    • Author(s)
      秀 道広、福永 淳、鈴木 孝幸、中村 紀子、木村 美音、笹島 隆義、高崎 真由美、家串 和真、五十嵐 敦之
    • Organizer
      第120回日本皮膚科学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 慢性蕁麻疹の鑑別と治療2021

    • Author(s)
      福永淳
    • Organizer
      第15回相模原臨床アレルギーセミナー
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 病型鑑別に力点をおいた蕁麻疹診療の実際と病態解明の進歩2021

    • Author(s)
      福永淳
    • Organizer
      第109回日本皮膚科学会大分地方会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] アドレナリン蕁麻疹の診断と治療2021

    • Author(s)
      福永淳
    • Organizer
      第51回日本皮膚免疫アレルギー学会総会学術大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Real-world safety and effectiveness of omalizumab in Japanese patients2021

    • Author(s)
      Atsushi Fukunaga, Michihiro Hide, Takayuki Suzuki, Noriko Nakamura, Mine Kimura, Takayoshi Sasajima, Mayumi Takasaki, Kazuma Iekushi, Atsuyuki Igarashi
    • Organizer
      2021 GA2LEN UCARE Urticaria Conference
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Solar urticaria: prognosis and DLQI change among 29 Japanese patients2021

    • Author(s)
      Shinya Imamura, Yoshiko Oda, Mayuko Mizuno, Mariko Suzuki, Ken Washio, Takeshi Fukumoto, Chikako Nishigori, Atsushi Fukunaga
    • Organizer
      2021 GA2LEN UCARE Urticaria Conference
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 汗アレルギーからみたコリン性蕁麻疹とアトピー性皮膚炎2020

    • Author(s)
      福永 淳
    • Organizer
      第119回日本皮膚科学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 慢性蕁麻疹の治療と病態解明の進歩2020

    • Author(s)
      福永 淳、織田 好子
    • Organizer
      JSA/WAO Joint Congress 2020(第69回日本アレルギー学会学術大会)(教育講演)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 3.日本におけるUCAREセンター(蕁麻疹国際診療センター)の現状と今後の課題~蕁麻疹患者の診断、治療、医療連携2020

    • Author(s)
      福永 淳
    • Organizer
      JSA/WAO Joint Congress 2020(第69回日本アレルギー学会学術大会)(Educational Seminar)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 蕁麻疹、血管性浮腫の診断と治療2020

    • Author(s)
      福永 淳
    • Organizer
      第4回日本アレルギー学会地方会近畿支部学術講演会(教育講演)
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Improved FcεRI-mediated basophil reactivities reflect rapid-responses to omalizumab in chronic spontaneous urticaria.2020

    • Author(s)
      Yoshiko Oda, Atsushi Fukunaga, Ken Washio, Shinya Imamura, Mayumi Hatakeyama, Kanako Ogura, Chikako Nishigori
    • Organizer
      JSA/WAO Joint Congress 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Efficacy and safety of Ligelizumab for CSU in Japanese patients: Subgroup analysis of Phase 2b study2020

    • Author(s)
      Hide M, Fukunaga A, Murakami M, Severin T, Igarashi A
    • Organizer
      JSA/WAO Joint Congress 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Book] アレルギー総合ガイドライン2022 蕁麻疹2022

    • Author(s)
      秀道広、中村陽一、福永 淳、猪又直子、高萩俊輔
    • Total Pages
      403
    • Publisher
      協和企画
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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