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Development of pharmacogenetic biomarkers of response to sublingual immunotherapy of house dust mite

Research Project

Project/Area Number 21K16827
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionUniversity of Fukui

Principal Investigator

Kidoguchi Masanori  福井大学, 学術研究院医学系部門, 助教 (30880132)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsアレルギー性鼻炎 / 舌下免疫療法 / 薬理遺伝学 / 全ゲノム関連解析
Outline of Research at the Start

スギ花粉症やダニ抗原アレルギー性鼻炎は近年増加傾向であり、日本人の2人に1人が罹患している国民病である。スギ花粉およびダニ抗原舌下免疫療法は唯一根治性のある治療として注目されているが、2年以上の長期治療にも関わらず効果が乏しい症例が一定数存在する。本研究では、ダニ抗原舌下免疫療法患者の遺伝子型と舌下免疫療法への応答性との関連を明らかにすることを目的とする。さらに、ダニ抗原舌下免疫療法の応答性が予測可能な薬理遺伝学的バイオマーカーの開発を目指す。

Outline of Final Research Achievements

This study aimed to determine the association between HLA genotype and response to sublingual immunotherapy (SLIT) in patients with house dust mite (HDM) SLIT and to develop a pharmacogenetic biomarker that could predict response to HDM SLIT. A total of 505 patients receiving HDM SLIT were enrolled. Symptom questionnaires were obtained from the study subjects before and after the start of SLIT to determine responses. Blood samples were collected from each patient, DNA was extracted, and genotyping was performed. In addition, whole genome imputation and HLA imputation were performed using the obtained data and Japanese reference data, and the association with response to HDM SLIT was analyzed.

Academic Significance and Societal Importance of the Research Achievements

スギ花粉症やダニ抗原アレルギー性鼻炎は近年増加傾向であり、日本人の2人に1人が罹患している国民病である。舌下免疫療法は唯一根治性のある治療として注目されている。本研究代表者は、以前にスギ花粉舌下免疫療法を行っているスギ花粉症患者において、HLA-DPB1*05:01遺伝子型を保有する患者は、保有しない患者と比較して、治療応答性が低いことを見出した。本研究では、ダニ抗原舌下免疫療法患者を対象とし実施し、治療応答性との関連を分析中で解析結果について検証を行っている段階である。本研究で得られる成果は、将来的にダニ抗原舌下免疫療法の応答性が予測可能な薬理遺伝学的バイオマーカーとなる可能性を秘めている。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (26 results)

All 2024 2023 2022 2021

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (18 results) (of which Int'l Joint Research: 4 results,  Invited: 8 results) Book (1 results)

  • [Journal Article] The current findings in eosinophilic chronic rhinosinusitis.2023

    • Author(s)
      Tsuda T, Suzuki M, Kato Y, Kidoguchi M, Kumai T, Fujieda S, Sakashita M.
    • Journal Title

      Auris Nasus Larynx.

      Volume: 51 Issue: 1 Pages: 51-60

    • DOI

      10.1016/j.anl.2023.08.002

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Middle meatus microbiome in patients with eosinophilic chronic rhinosinusitis in a Japanese population2023

    • Author(s)
      Kidoguchi M, Imoto Y, Noguchi E, Nakamura T, Morii W, Adachi N, Ii R, Koyama K, Aoki S, Miyashita K, Hosokawa Y, Omura K, Tanaka Y, Tanaka K, Hida Y, Ninomiya T, Kato Y, Sakashita M, Takabayashi T, Fujieda S.
    • Journal Title

      J Allergy Clin Immunol.

      Volume: 152 Issue: 6 Pages: 1669-1676

    • DOI

      10.1016/j.jaci.2023.06.029

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 遺伝子型に基づく鼻副鼻腔疾患の治療戦略2022

    • Author(s)
      木戸口 正典
    • Journal Title

      Nippon Jibiinkoka Tokeibugeka Gakkai Kaiho(Tokyo)

      Volume: 125 Issue: 11 Pages: 1538-1541

    • DOI

      10.3950/jibiinkotokeibu.125.11_1538

    • ISSN
      2436-5793, 2436-5866
    • Year and Date
      2022-11-20
    • Related Report
      2022 Research-status Report
  • [Journal Article] HLA‐DPB1*05:01 genotype is associated with poor response to sublingual immunotherapy for Japanese cedar pollinosis2022

    • Author(s)
      Kidoguchi Masanori、Morii Wataru、Noguchi Emiko、Yuta Atsushi、Ogawa Yukiko、Nakamura Takako、Kikuoka Hirotaka、Kouzaki Hideaki、Arai Hiroyuki、Ii Rieko、Adachi Naoto、Koyama Keisuke、Ninomiya Takahiro、Imoto Yoshimasa、Sakashita Masafumi、Fujieda Shigeharu
    • Journal Title

      Allergy

      Volume: 77 Issue: 5 Pages: 1633-1635

    • DOI

      10.1111/all.15254

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pharmacogenetics of HLA gene polymorphisms in predicting response to Japanese cedar pollen sublingual immunotherapy2022

    • Author(s)
      木戸口 正典
    • Journal Title

      Journal of Immunology, Allergy and Infection in Otorhinolaryngology

      Volume: 2 Issue: 4 Pages: 137-139

    • DOI

      10.24805/jiaio.2.4_137

    • ISSN
      2435-7952
    • Related Report
      2022 Research-status Report
  • [Journal Article] Elevated Serum Leptin Levels in Patients With Eosinophilic Chronic Rhinosinusitis2022

    • Author(s)
      Imoto Yoshimasa、Ueki Shigeharu、Kato Yukinori、Yoshida Kanako、Morikawa Taiyo、Kimura Yukihiro、Kidoguchi Masanori、Tsutsumiuchi Toshiki、Koyama Keisuke、Adachi Naoto、Ito Yumi、Ogi Kazuhiro、Sakashita Masafumi、Yamada Takechiyo、Schleimer Robert P.、Takabayashi Tetsuji、Fujieda Shigeharu
    • Journal Title

      Frontiers in Pharmacology

      Volume: 12 Pages: 793607-793607

    • DOI

      10.3389/fphar.2021.793607

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of salivary microbiome in IL‐10 production and efficacy of sublingual immunotherapy2021

    • Author(s)
      Oka Aiko、Kidoguchi Masanori、Kariya Shin、Fujiwara Tazuko、Yuta Atsushi、Miyashita Hiromi、Higaki Takaya、Ogawa Yukiko、Kanai Kengo、Makihara Sei‐ichiro、Haruna Takenori、Kunisawa Jun、Adachi Naoto、Koyama Keisuke、Ii Rieko、Noguchi Emiko、Fujieda Shigeharu、Nishizaki Kazunori、Okano Mitsuhiro
    • Journal Title

      Allergy

      Volume: - Issue: 8 Pages: 2617-2620

    • DOI

      10.1111/all.14858

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Repressive effects of Lipopolysaccharide from Fusobacterium nucleatum on epithelial type 2 inflammation in eosinophilic chronic rhinosinusitis2024

    • Author(s)
      Masanori Kidoguchi、Yoshimasa Imoto、Emiko Noguchi、Shigeharu Fujieda
    • Organizer
      American Academy of Allergy Asthma & Immunology (AAAAI) annual meeting 2024
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] スギ花粉舌下免疫療法の応答性を予測する薬理遺伝学的予測モデルの開発2023

    • Author(s)
      木戸口 正典
    • Organizer
      第72回 日本アレルギー学会学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 舌下免疫療法のプレシジョンメディシン2022

    • Author(s)
      木戸口正典
    • Organizer
      第123回 日本耳鼻咽喉科頭頸部外科学会総会・学術講演会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 遺伝子研究をはじめてみよう2022

    • Author(s)
      木戸口正典
    • Organizer
      第2回 日本耳鼻咽喉科免疫アレルギー感染症学会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 鼻茸のエンドタイプ診断パネル開発と個別化医療への応用2022

    • Author(s)
      木戸口正典
    • Organizer
      第61回 日本鼻科学会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] HLA-DPB1*05:01 genotype is a predictive biomarker of sublingual immunotherapy response for Japanese cedar pollinosis2022

    • Author(s)
      Masanori Kidoguchi, Wataru Morii1, Emiko Noguchi, Atsushi Yuta, Yukiko Ogawa, Takako Nakamura, Hirotaka Kikuoka, Hideaki Kouzaki, Hiroyuki Arai, Rieko Ii, Naoto Adachi, Keisuke Koyama, Takahiro Ninomiya, Yoshimasa Imoto, Masafumi Sakashita, and Shigeharu Fujieda
    • Organizer
      第71回 日本アレルギー学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] HLA-DPB1*05:01遺伝子型がスギ花粉舌下免疫療法の応答性が低いことに関与する2022

    • Author(s)
      木戸口正典
    • Organizer
      第9回 日本アレルギー学会 総合アレルギー講習会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] HLA-DPB1*05:01 genotype is a predictive biomarker of sublingual immunotherapy response for Japanese cedar pollinosis2022

    • Author(s)
      Masanori Kidoguchi、Emiko Noguchi、Atsushi Yuta、Shigeharu Fujieda
    • Organizer
      American Academy of Allergy Asthma & Immunology 2022 annual meeting
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] The association between the human microbiome in the nasal cavity and the number of sensitization in allergic rhinitis2022

    • Author(s)
      Keisuke Koyama、Masanori Kidoguchi、Naoto Adachi、Rieko Ii、Yukihiro Kimura、Kazuhiro Ogi、Masafumi Sakashita、Emiko Noguchi、Shigeharu Fujieda
    • Organizer
      18th Japan-Korea Joint Meeting of Otorhinolaryngology - Head and Neck Surgery
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] アレルギー性鼻炎における鼻腔・唾液・便のマイクロバイオーム2022

    • Author(s)
      小山佳祐、木戸口正典、足立直人、井伊里恵子、坂下雅文、野口恵美子、藤枝重治
    • Organizer
      第2回 耳鼻咽喉科免疫アレルギー感染症学会
    • Related Report
      2021 Research-status Report
  • [Presentation] アレルギー性鼻炎と鼻腔マイクロバイオーム2022

    • Author(s)
      木戸口正典
    • Organizer
      第2回 耳鼻咽喉科免疫アレルギー感染症学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 次世代シークエンサーを用いた好酸球性副鼻腔炎の鼻腔真菌叢解析2022

    • Author(s)
      足立直人、木戸口正典、井伊里恵子、小山佳祐、意元義政、坂下雅文、高林哲司、田中康広、野口恵美子、藤枝重治
    • Organizer
      第2回 耳鼻咽喉科免疫アレルギー感染症学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 好酸球性中耳炎のマイクロバイオーム解析2022

    • Author(s)
      井伊里恵子、足立直人、木戸口正典、野村彩美、高畑淳子、小山佳祐、宮本秀高、 廣瀬由紀、岡本昌之、野口恵美子、藤枝重治、松原 篤、田渕経司
    • Organizer
      第2回 耳鼻咽喉科免疫アレルギー感染症学会
    • Related Report
      2021 Research-status Report
  • [Presentation] HLA遺伝子多型によるスギ花粉舌下免疫療法の応答性を予測する薬理遺伝学的検討2021

    • Author(s)
      木戸口正典、藤枝重治
    • Organizer
      第1回 日本耳鼻咽喉科免疫アレルギー感染症学会
    • Related Report
      2021 Research-status Report
  • [Presentation] HLA遺伝子多型による舌下免疫療法の新たな薬理遺伝学的バイオマーカー2021

    • Author(s)
      木戸口正典
    • Organizer
      第60回 日本鼻科学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Association between the NOS2 pentanucleotide repeat polymorphism and risk of postoperative recurrence of chronic rhinosinusitis with nasal polyps in a Japanese population2021

    • Author(s)
      Masanori Kidoguchi、Emiko Noguchi、Shigeharu Fujieda
    • Organizer
      The 29th Congress of The European Rhinologic Society
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 増悪を繰り返す喉頭アレルギーに著効した舌下免疫療法の1例2021

    • Author(s)
      木戸口正典、足立直人、井伊里恵子、田渕経司、意元義政、坂下雅文、藤枝重治
    • Organizer
      第70回 日本アレルギー学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 鼻副鼻腔疾患と細菌叢2021

    • Author(s)
      藤枝重治、小山佳祐、足立直人、木戸口正典
    • Organizer
      第122回 日本耳鼻咽喉科学会総会・学術講演会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Book] JOHNS39巻2号(2月号)副鼻腔炎診療は変わったか?2023

    • Author(s)
      木戸口正典、ほか
    • Total Pages
      116
    • Publisher
      東京医学社
    • ISBN
      9784885635649
    • Related Report
      2022 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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