Study of Adjuvant Immunotherapy for Allergic Diseases

• Project/Area Number: 18K09360
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Nippon Medical School
• Principal Investigator: OKUBO KIMIHIRO 日本医科大学, 大学院医学研究科, 大学院教授 (10213654)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: スギ花粉症 / アレルゲン免疫療法 / バイオマーカー / 〇スギ花粉症 / 花粉症 / アジュバント / モデル動物 / アレルギー性鼻炎 / 免疫療法

Outline of Final Research Achievements

Allergen immunotherapy for allergic rhinitis is characterized by the fact that, unlike drug therapy, its effects persist even after treatment is stopped. We found that the post-treatment mechanism of this effect is analogous to the balance of specific IgE and specific IgG4 antibody production. In sublingual immunotherapy for cedar pollinosis, we found that IgE decreased to the same level as placebo at the end of treatment, whereas IgG4 increased after treatment, and IgG4 production continued to increase in response to cedar pollen dispersal. In addition, the higher the level of Il-10 among serum cytokines before sublingual immunotherapy, the more IgG4 remained elevated.

Academic Significance and Societal Importance of the Research Achievements

アレルゲン免疫療法の特徴である後効果に関しての基礎的な検討は少ない。我々はこの後効果発現機序を特異的IgE、特異的IgG4抗体産生のバランスにより類推できることを見出した。これによりアレルゲン免疫療法を実施する患者の抗原特異的IgE、IgG4産生の追跡により、その患者が治療を止めた後も、どの程度治療後効果が継続できるか類推可能となる。このことにより治療継続期間、後効果の継続程度で医療資源の減少を導き、医療費の削減できる可能性を示唆した。

Research Products

• [Journal Article] Disease-modifying effect of Japanese cedar pollen sublingual immunotherapy tablets. (2022)
  • Author(s): Yonekura S, Gotoh M, Kaneko S, Maekawa Y, Okubo K, Okamoto Y
  • Journal Title: J Allergy Clin Immunol in Pract. Volume: 9 Issue: 11 Pages: 4103-4116
  • DOI: 10.1016/j.jaip.2021.06.060
• [Journal Article] Long-term sublingual immunotherapy provides better effects for patients with Japanese cedar pollinosis (2021)
  • Author(s): Hamada Satoko、Kobayashi Yoshiki、Sakamoto Daiki、Shimamura Akihiro、Kuroda Kazumichi、Kawachi Risaki、Kanda Akira、Asako Mikiya、Gotoh Minoru、Okubo Kimihiro、Tomoda Koichi、Iwai Hiroshi
  • Journal Title: Auris Nasus Larynx Volume: － Issue: 4 Pages: 646-652
  • DOI: 10.1016/j.anl.2021.01.003
  • Peer Reviewed / Open Access
• [Journal Article] Long-term treatment of Japanese cedar pollinosis with Japanese cedar pollen SLIT drops and persistence of treatment effect: A post-marketing clinical trial (2021)
  • Author(s): Nomura Y, Okubo K, Nakamura T, Sawaki S, Kitagou H, Idei N, Kaneko S, Kobayashi S, Tanaka Y, Okamoto Y
  • Journal Title: Allergology International Volume: 70 Issue: 1 Pages: 96-104
  • DOI: 10.1016/j.alit.2020.05.008
  • NAID: 130007966818
  • ISSN: 1323-8930, 1440-1592
• [Journal Article] Add on omalizumab for inadequently controlled severe pollinosis despite standard-of-care; a randomized study. (2020)
  • Author(s): Okubo K, Okano M, Sato N, Tamaki Y, Suzuki H, Uddin A, Fogel R
  • Journal Title: J Allergy Clin Immunol Pract. Volume: 8(9) Issue: 9 Pages: 3130-3140.e2
  • DOI: 10.1016/j.jaip.2020.04.068
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Decreased numbers of metachromatic cells in nasal swabs in Japanese cedar pollinosis following sublingual immunotherapy. (2020)
  • Author(s): Otsuka K, Otsuka H, Matsune S, Okubo K
  • Journal Title: Immun Inflamm Dis Volume: 8(3) Issue: 3 Pages: 333-341
  • DOI: 10.1002/iid3.314
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long-term efficacy and dose-finding trial of Japanese cedar pollen SLIT tablet. (2019)
  • Author(s): Gotoh M, Yonekura S, Imai T, Kaneko S, Horikawa E, Konno A, Okamoto Y, Okubo K
  • Journal Title: J Allergy Clin Immunol Pract Volume: 7 Issue: 4 Pages: 1287-1297
  • DOI: 10.1016/j.jaip.2018.11.044
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Anti-Inflammatory Effects of EM900 on Cultured Human Nasal Epithelial Cells (2018)
  • Author(s): Wakayama N, Matsune S, Takahara E, Sekine K, Yoshioka Y, Ishida M, Yamaguchi S, Okubo K, Sunazuka T, Omura S
  • Journal Title: Journal of Nippon Medical School Volume: 85 Issue: 5 Pages: 265-270
  • DOI: 10.1272/jnms.JNMS.2018_85-42
  • NAID: 130007520433
  • ISSN: 1345-4676, 1347-3409
  • Year and Date: 2018-10-15
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serum Cytokine Interactions Are Implicated in the Mechanism of Action of Sublingual Immunotherapy for Japanese Cedar Pollinosis (2018)
  • Author(s): Shimada K, Gotoh M, Okubo K, Hiroi T, Kaminuma O, Nakaya A
  • Journal Title: Journal of Nippon Medical School Volume: 85 Issue: 5 Pages: 250-258
  • DOI: 10.1272/jnms.JNMS.2018_85-40
  • NAID: 130007520427
  • ISSN: 1345-4676, 1347-3409
  • Year and Date: 2018-10-15
  • Peer Reviewed / Open Access / Int'l Joint Research