Development of a preventive strategy for allergic diseases

• Project/Area Number: 18H02850
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Saito Hirohisa 国立研究開発法人国立成育医療研究センター, 所長室, 研究所長補佐 (40130166)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 発症予防 / アレルギー疾患 / 抗IgE抗体

Outline of Final Research Achievements

We found that the administration of anti-IgE antibody to pregnant mouse suppressed the production of antigen-specific IgE antibody in pups and thus prevent the development of food allergy. On the other hand, other immune responses such as antigen-specific T cell responses and IgG antibody production were not altered, which indicated the effect of anti-IgE antibody is IgE specific. Although the duration of the effect of anti-IgE antibody varied depending on the mouse strains, inhibition of IgE antibody production was observed in all strains. In addition, the administration of anti-IgE antibody during the neonatal period showed comparable effect with those in the pregnancy period. Taken together, the administration of anti-IgE antibody during pregnancy or neonatal period could be a promising strategy to prevent allergic diseases in children.

Academic Significance and Societal Importance of the Research Achievements

アレルギー疾患の患者数が増え続けており、現在では国民の3人に1人が何らかのアレルギーを持っていると言われています。一旦発症したアレルギー疾患を完全に治すことができる治療は存在しないため、アレルギー疾患の発症を抑制する方法の開発が期待されています。本研究では、妊娠中のマウスに抗IgE抗体を投与すると、生まれてきた仔マウスが一定期間IgE抗体を産生しないこと、その結果、仔マウスにおいて食物アレルギーの発症を予防できることを明らかにしました。本方法はIgE抗体以外の免疫系には影響がないことから、実現可能なアレルギー疾患発症予防法になり得る可能性がある。今後、臨床応用を目指した検討を行う必要がある。

Research Products

• [Journal Article] Landmark papers in our journal: Articles I to III of the series describing the discovery of IgE by the Ishizakas. (2019)
  • Author(s): Saito H, Renz H.
  • Journal Title: J Allergy Clin Immunol Volume: 144 Issue: 5 Pages: 1163-1165
  • DOI: 10.1016/j.jaci.2019.08.026
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Obituary for Teruko Ishizaka (1926-2019) (2019)
  • Author(s): Saito H, Galli SJ.
  • Journal Title: Allergology International Volume: 68 Issue: 4 Pages: 399-400
  • DOI: 10.1016/j.alit.2019.07.001
  • NAID: 130007733172
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] IgE-class-specific immunosuppression in offspring by administration of anti-IgE to pregnant mice (2019)
  • Author(s): Morita H, Tamari M, Fujiwara M, Motomura K, Koezuka Y, Ichien G, Matsumoto K, Ishizaka K, Saito H.
  • Journal Title: J Allergy Clin Immunol Volume: 143 Issue: 3 Pages: 1261-1264
  • DOI: 10.1016/j.jaci.2018.11.008
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Administration of anti-IgE to pregnant mice caused IgE-class-specific immunosuppression in offspring (2019)
  • Author(s): Hideaki Morita, Masato Tamari, Masako Fujiwara, Kenichiro Motomura, Yasuhiko Koezuka, Go Ichien, Kenji Matsumoto, Kimishige Ishizaka, Hirohisa Saito
  • Organizer: American Academy of Allergy and Immunology, 2019 Annual Meeting
  • Int'l Joint Research