Role of Local Immunoglobulin E Production in the Pathophysiology of Eosinophilic Chronic Rhinosinusitis

• Project/Area Number: 15K20201
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Osaka University
• Principal Investigator: Takeda Kazuya 大阪大学, 医学部附属病院, 医員 (90734054)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 好酸球性副鼻腔炎 / IgE / 鼻腔細菌 / Th2細胞 / クラススイッチ / 鼻茸 / IｇE / アレルギー / モノクローナル抗体 / Th2 / 常在菌 / 体細胞超変異 / 鼻副鼻腔常在菌

Outline of Final Research Achievements

We generated monoclonal antibodies from IgE+ plasmablasts of nasal polyps(NPs) of ECRS patients. In the reactivity tests, we found that ~20% of expressed antibodies reacted with nasal bacteria. In vitro T cell stimulation assay with identified antigens revealed that patients had more bacteria-reactive Th2 cells than healthy individuals. High-throughput sequencing analysis unraveled that local IgEs were originated from polyp-residing IgG+ and/or IgA+ B cells. These results suggest that protective mucosal immunity against nasal bacteria might convert into allergic inflammation through IgE class-switching in ECRS patients.

Research Products

• [Presentation] 好酸球性副鼻腔炎における鼻茸局所IgE産生を中心とした獲得免疫応答について (2018)
  • Author(s): 武田和也 識名崇 端山昌樹 前田陽平 津田武 猪原秀典
  • Organizer: 第37回日本耳鼻咽喉科免疫アレルギー学会
• [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茸中B細胞レパトアの網羅的解析 (2017)
  • Author(s): 武田和也 識名崇 端山昌樹 前田陽平 津田武 猪原秀典
  • Organizer: 第36回日本耳鼻咽喉科免疫アレルギー学会
• [Presentation] 好酸球性副鼻腔炎の鼻茸局所IgE産生細胞の分化過程の検討 鼻茸中B細胞受容体レパトア解析 (2017)
  • Author(s): 武田和也 識名崇 端山昌樹 前田陽平 津田武 猪原秀典
  • Organizer: 第66回日本アレルギー学会学術大会
• [Presentation] Tracking allergen-reactive IgE+ B cells in patients with eosinophilic chronic rhinosinusitis (2016)
  • Author(s): 武田和也, 榊原修平, 菊谷 仁
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 沖縄
  • Year and Date: 2016-12-05
• [Presentation] Identification of nasal resident bacteria as causative allergens in eosinophilic chronic rhinosinusitis (2016)
  • Author(s): Kazuya Takeda, Shuhei Sakakibara, Daisuke Motooka, Shota Nakamura, Kazuo Yamashita, Daron Standley, Masaki Hayama, Takashi Shikina, Hidenori Inohara, Hitoshi Kikutani
  • Organizer: 16th International Congress of Immunology
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Identification of nasal resident bacteria as causative allergens in chronic rhinosinusitis with nasal polyps (2016)
  • Author(s): Kazuya Takeda, Shuhei Sakakibara, Takashi Shikina, Masaki Hayama, Yohei Maeda, Suzuyo Okazaki, Hitoshi Kikutani, Hidenori Inohara
  • Organizer: 26th Congress of the European Rhinologic Society / 33th International Symposium on Infection and Allergy of the Nose
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2016-07-02
  • Int'l Joint Research
• [Presentation] 患者組織由来組換えIgE抗体を用いた好酸球性副鼻腔炎のアレルゲン同定 (2016)
  • Author(s): 武田和也, 識名 崇, 端山昌樹, 岡崎鈴代, 前田陽平, 猪原秀典
  • 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: 2016-06-17
• [Presentation] 好酸球性副鼻腔炎における鼻副鼻腔常在菌の関与について：鼻茸組織由来モノクローナル抗体を用いた検討 (2016)
  • Author(s): 武田和也, 識名 崇, 端山昌樹, 岡崎鈴代, 前田陽平, 増村千佐子, 猪原秀典
  • Organizer: 第34回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 鳥羽
  • Year and Date: 2016-02-04
• [Presentation] Idenification of eosinophilic chronic rhinosinusitis (2015)
  • Author(s): 武田和也, 榊原修平, 菊谷 仁
  • Organizer: 第44回日本免疫学会
  • Place of Presentation: 札幌
  • Year and Date: 2015-11-18
• [Presentation] 鼻茸組織由来IgEモノクローナル抗体作製による局所産生IgEの特異的抗原の同定 (2015)
  • Author(s): 武田和也, 識名 崇, 端山昌樹, 岡崎鈴代, 前田陽平, 増村千佐子, 猪原秀典
  • Organizer: 第54回日本鼻科学会 平成27年10月1-3日, 広島
  • Place of Presentation: 広島
  • Year and Date: 2015-10-01