2021 Fiscal Year Research-status Report
気管支喘息に対する生物学的製剤がもたらす免疫調節作用の解明
Project/Area Number |
20K08549
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Research Institution | Juntendo University |
Principal Investigator |
原田 紀宏 順天堂大学, 医学部, 准教授 (10465065)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 気管支喘息 / 生物学的製剤 / 免疫 |
Outline of Annual Research Achievements |
吸入ステロイド薬により、喘息の症状管理は格段に改善しているが、喘息が完治することは考え難い。そのようななかにおいて、生物学的製剤の登場により薬剤使用下の臨床的完解の可能性が議論されるようになった。喘息患者の10%ほどを占める難治性喘息患者には、ステロイド抵抗性を有する患者も多く、それらの患者では吸入ステロイド薬の効果は限定的である。このような既存治療で喘息症状管理が不十分な重症喘息に対して、抗IgE抗体製剤オマリズマブ、抗IL-5抗体製剤メポリズマブ、抗IL-5受容体α抗体製剤ベンラリズマブ、抗IL-4受容体α抗体製剤デュピルマブの4つの生物学的製剤が本邦で使用可能である。既に10年以上の使用歴のある抗IgE抗体製剤では、高親和性IgE受容体の発現低下や末梢血リンパ球分画がTh2優位にシフトする可能性が報告されている。このように特定の分子を抑制する生物学的製剤が生体に及ぼす免疫調節作用については明らかではない。本研究においては、生物学的製剤治療の免疫調節作用を明らかにし、喘息病態の解明、各生物学的製剤に対する新規バイオマーカーや喘息に対する新規治療標的分子の開発を目指している。現時点で、既存の治療で管理不十分な喘息患者に対して生物学的製剤が使用された喘息患者が100例を超えて登録されている。2021年度は、デュピルマブ治療1年間における各種パラメーターの動向を解析し、末梢血好酸球、好塩基球、type 3 innate lymphoid cells、natural killer細胞の有意な増加、および、血清総IgE値、TARC、FeNO、type 1 innate lymphoid cellsの有意な減少を認めた。また、メポリズマブ、および、ベンラリズマブの治療1年後の有効例または臨床的寛解例を予測するバイオマーカーを解析し、末梢血のリンパ球分画の有用性を明らかにした。
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Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
2021年度までに、メポリズマブ、および、ベンラリズマブの生物学的製剤の末梢血単核球のフローサイトメトリーや血清タンパクの解析を行い論文投稿準備中である。平行して実施している皮脂RNA解析に関しても発表予定まで解析をすすめている。一方、デュピルマブ治療に関する症例集積とシングルセルRNAシークエンス解析がやや遅れている。
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Strategy for Future Research Activity |
2022年度は、更なる症例、検体の集積、皮脂RNA解析、シングルセルRNAシークエンス解析を行い、治療による変化を評価する。とくに症例集積が遅れていたデュピルマブに関して、治療前のデータと治療効果を解析し、喘息病態の解明と治療効果を予測する新規バイオマーカーの確立を目指す。
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[Presentation] Novel predictive biomarkers for mepolizumab treatment in patients with severe asthma2021
Author(s)
Hitoshi Sasano, Norihiro Harada, Yuuki Sandhu, Yuki Tanabe, Sonoko Harada, Takayasu Watanabe, Yoshihiko Sato, Takayasu Nishimaki, Sumiko Abe, Shoko Ueda, Tomohito Takeshige, Kei Matsuno, Jun Ito, Tetsutaro Nagaoka, Ryo Atsuta, Asako Chiba, Hisaya Akiba, Kenji Izuhara, Sachiko Miyake, Kazuhisa Takahashi
Organizer
The 25th congress of the Asian Paciffic Society of Respirology
Int'l Joint Research
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[Presentation] A Study of lymphocyte fraction in bronchoalveolar lavage fluid in interstitial lung disease2021
Author(s)
Sonoko Harada, Norihiro Harada, Tomohito Takeshige, Hitoshi Sasano, Yuuki Sandhu, Yuki Tanabe, Kei Matsuno, Shun Shinomiya, Motoyasu Kato, Jun Ito, Kazuyuki Nakagome, Makoto Nagata, Kazuhisa Takahashi
Organizer
The 25th congress of the Asian Paciffic Society of Respirology
Int'l Joint Research
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[Presentation] Analysis of lymphocyte fractions in bronchoalveolar lavage fluid in chronic eosinophilic pneumonia2021
Author(s)
Sonoko Harada, Norihiro Harada, Tomohito Takeshige, Hitoshi Sasano, Yuuki Sandhu, Yuki Tanabe, Kei Matsuno, Shun Shinomiya, Motoyasu Kato, Jun Ito, Kazuyuki Nakagome, Makoto Nagata, Kazuhisa Takahashi
Organizer
The 25th congress of the Asian Paciffic Society of Respirology
Int'l Joint Research
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[Presentation] Japanese cedar pollen sublingual immunotherapy for asthma patients with Japanese cedar pollinosis provided stability of symptoms of asthma in the off-season2021
Author(s)
Shoko Ueda, Jun Ito, Yuuki Sandhu, Takayasu Watanabe, Yoshihiko Sato, Takayasu Nishimaki, Yukari Kato, Sumiko Abe, Hitoshi Sasano, Yuki Tanabe, Tomohito Takeshig1, Sonoko Harada, Ryo Atsuta, Norihiro Harada, Kazuhisa Takahashi
Organizer
The 25th congress of the Asian Paciffic Society of Respirology
Int'l Joint Research
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[Presentation] Steroid-resistant airway inflammation in mice induced by chitin2021
Author(s)
Tomohito Takeshige, Norihiro Harada, Sonoko Harada, Ayako Ishimori, Yoko Katsura, Hitoshi Sasano, Yuuki Sandhu, Kei Matsuno, Fumihiko Makino, Jun Ito, Ryo Atsuta, Hisaya Akiba, Kazuhisa Takahashi
Organizer
The 25th congress of the Asian Paciffic Society of Respirology
Int'l Joint Research
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[Presentation] Effects of one-year of dupilumab treatment in patients with severe asthma2021
Author(s)
Sumiko Abe, Norihiro Harada, Yuuki Sandhu, Hitoshi Sasano, Yuuki Tanabe, Sonoko Harada, Ai Goto, Takayasu Watanabe, Yoshihiko Sato, Takayasu Nishimaki, Yukari Kato, Shoko Ueda, Tomohito Takeshige, Jun Ito, Ryo Atsuta, Kazuhisa Takahashi
Organizer
The 25th congress of the Asian Paciffic Society of Respirology
Int'l Joint Research
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[Presentation] The usefulness of CT images in evaluating the effects of bronchial thermoplasty in patients with severe asthma2021
Author(s)
Sumiko Abe, Mina Yasuda, Kazunori Tobino, Sonoko Harada, Hitoshi Sasano, Yuuki Sandhu, Tomohito Takeshige, Kei Matsuno, Tetsuhiko Asao, Takuto Sueyasu, Saori Nishizawa, Kohei Yoshimine, Yuki Ko, Yuki Yoshimatsu, Kosuke Tsuruno, Hiromi Ide, Haruhi Takagi, Tetsutaro Nagaoka, Norihiro Harada, Kazuhisa Takahashi
Organizer
The 25th congress of the Asian Paciffic Society of Respirology
Int'l Joint Research
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[Presentation] A study of severe asthma patients who continued omalizumab treatment for more than 3 years2021
Author(s)
Ai Goto, Norihiro Harada, Yuuki Sandhu, Hitoshi Sasano, Yuki Tanabe, Sonoko Harada, Takayasu Watanabe, Yoshihiko Sato, Takayasu Nishimaki, Yukari Kato, Sumiko Abe, Shoko Ueda, Tomohito Takeshige, Kei Matsuno, Jun Ito, Tetsutaro Nagaoka, Ryo Atsuta, Kazuhisa Takahashi
Organizer
The 25th congress of the Asian Paciffic Society of Respirology
Int'l Joint Research
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[Presentation] One-year treatment with benralizumab in patients with severe asthma2021
Author(s)
Yuuki Sandhu, Norihiro Harada, Hitoshi Sasano, Sumiko Abe, Sonoko Harada, Takayasu Watanabe, Yoshihiko Sato, Takayasu Nishimaki, Yukari Kato, Shoko Ueda, Yuki Tanabe, Tomohito Takeshige, Tetsutaro Nagaoka, Jun Ito, Ryo Atsuta, Kazuhisa Takahashi
Organizer
The 25th congress of the Asian Paciffic Society of Respirology
Int'l Joint Research
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[Presentation] A study of severe asthma patients who continued mepolizumab treatment for more than 3 years2021
Author(s)
Takayasu Nishimaki, Norihiro Harada, Ai Goto, Yuuki Sandhu, Hitoshi Sasano, Yuki Tanabe, Sonoko Harada, Takayasu Watanabe, Yoshihiko Sato, Yukari Kato, Sumiko Abe, Shoko Ueda, Tomohito Takeshige, Kei Matsuno, Jun Ito, Nagaoka Tetsutaro, Atsuta Ryo, Kazuhisa Takahashi
Organizer
The 25th congress of the Asian Paciffic Society of Respirology
Int'l Joint Research
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[Presentation] The prevalence of Obstructive Sleep Apnea in Japanese patients with asthma2021
Author(s)
Mina Yasuda, Kazunori Tobino, Norihiro Harada, Ryunosuke Ooi, Takuto Sueyasu, Saori Nishizawa, Kohei Yoshimine, Yuki Ko, Yuki Yoshimatsu, Kosuke Tsuruno, Hiromi Ide, Kazuhisa Takahashi
Organizer
The 25th congress of the Asian Paciffic Society of Respirology
Int'l Joint Research
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[Presentation] A novel mechanism for TWEAK induces the production of TSLP, RANTES, and TARC in BEAS-2B human bronchial epithelial cells during epithelial-mesenchymal transition2021
Author(s)
Kei Matsuno, Norihiro Harada, Tomohito Takeshige, Sonoko Harada, Ayako Ishimori, Yukinari Itoigawa, Yoko Katsura, Yuzo Kodama, Fumihiko Makino, Jun Ito, Ryo Atsuta, Hisaya Akiba, Kazuhisa Takahashi
Organizer
The 25th congress of the Asian Paciffic Society of Respirology
Int'l Joint Research
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[Presentation] Role of MAP3K19 in allergic airway inflammation of asthma2021
Author(s)
Yuuki Sandhu, Norihiro Harada, Sonoko Harada, Hitosh. Sasano, Tomohito Takeshige, Kei Matsuno, Ayako Ishimori, Yoko Katsura, Jun Ito, Hisaya Akiba, Kazuhisa Takahashi
Organizer
The 25th congress of the Asian Paciffic Society of Respirology
Int'l Joint Research
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[Presentation] Clinical and immunological effect of mepolizumab treatment in patients with severe asthma2021
Author(s)
Hitoshi Sasano, Norihiro Harada, Yuuki Sandhu, Yuki Tanabe, Sonoko Harada, Takayasu Watanabe, Yoshihiko Sato, Takayasu Nishimaki, Yukari Oyama, Sumiko Abe, Shoko Ueda, Tomohito Takeshige, Kei Matsuno, Jun Ito, Kazuhisa Takahashi
Organizer
American Thoracic Society International Conference 2021
Int'l Joint Research
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