Immunological analysis of the mechanism of oral immunotherapy for food allergy.

• Project/Area Number: 23591555
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Fujita Health University
• Principal Investigator: TSUGE Ikuya 藤田保健衛生大学, 医学部, 教授 (00231431)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 経口免疫療法 / アレルゲン特異的T細胞 / 好塩基球活性化 / アレルゲン免疫療法 / CD154 / IL-4 / IL-5 / IFN-γ / Foxp3 / 低アレルゲン化食品 / 好塩基球活性化試験 / 鶏卵アレルギー

Research Abstract

We analyzed the mechanism of oral immunotherapy for food allergy immunologically, with the aim to establish a safe oral immunotherapy. In this study, we evaluated allergen-specific T cells and the activation of basophils in immunotherapy using hypo-allergic hydrolyzed milk. Milk allergen specific T cells were identified as CD154 positive cells after allergen stimulation, and intracytoplasmic cytokines were simultaneously analyzed by multi-color flow-cytometry (Galios). As a result, the milk allergic patients, compared to non-milk allergic patients, milk allergen-specific Th2 cytokine producing cells have increased significantly, and milk allergen-specific IL-4 producing cells were positively correlated with milk specific IgE. On the other hand, in the analysis of basophils, the reduction of Syk involved in signal from Fc epsilon RI was observed after immunotherapy, although the number of cases is still small. It is under investigation by increasing the number of cases currently.

Research Products

• [Journal Article] Acute eosinophilic pneumonia occurring in a dedicator of cytokinesis 8 (DOCK8) deficient patient (2014)
  • Author(s): Tsuge I, Ito K, Ohye T, Kando N, Kondo Y, Nakajima Y, Inuo C, Kurahashi H, Urisu A.
  • Journal Title: Pediatr Pulmonol Volume: 49
  • Peer Reviewed
• [Journal Article] Food sensitization in Japanese infants is associated with a common Filaggrin variant (2013)
  • Author(s): Nomura T, Tsuge I, Inuo C, Nakajima Y, Kondo Y, Sugiura S, Murata H, Iguchi T,Terada A, Saitoh S, Hashimoto S, Urisu A.
  • Journal Title: Ann Allergy Asthma Immunol Volume: 110 Pages: 388-390
  • Peer Reviewed
• [Journal Article] Effect of Japanese cedar specific immunotherapy on allergen-specific T(H)2 cells in peripheral blood (2013)
  • Author(s): Nomura T, Tsuge I, Inuo C, Nakajima Y, Tanaka K, Naruse N, Suzuki S, Ando H, Kondo Y, Saitoh S, Urisu A.
  • Journal Title: Ann Allergy Asthma Immunol Volume: 110 Pages: 380-385
  • Peer Reviewed
• [Journal Article] Anaphylactic reaction to dietary oats (2013)
  • Author(s): Inuo C, Kondo Y, Itagaki Y, Kurihara K, Tsuge I, Yoshikawa T, Urisu A.
  • Journal Title: Ann Allergy Asthma Immunol Volume: 110 Pages: 305-6
  • Peer Reviewed
• [Journal Article] Effect of Japanese cedar specific immunotherapy on allergen-specific T(H)2 cells in peripheral blood. (2013)
  • Author(s): Nomura T, Tsuge I, Inuo C, Nakajima Y, Tanaka K, Naruse N, Suzuki S, Ando H, Kondo Y, Saitoh S, Urisu A.
  • Journal Title: Ann Allergy Asthma Immunol. Volume: 110 Issue: 5 Pages: 380-385
  • DOI: 10.1016/j.anai.2013.02.015
  • Peer Reviewed
• [Journal Article] Food sensitization in Japanese infants is associated with a common Filaggrin variant. (2013)
  • Author(s): Nomura T, Tsuge I, Inuo C, Nakajima Y, Kondo Y, Sugiura S, Murata H, Iguchi T, Terada A, Saitoh S, Hashimoto S, Urisu A.
  • Journal Title: Ann Allergy Asthma Immunol. Volume: 110 Issue: 5 Pages: 388-390
  • DOI: 10.1016/j.anai.2013.02.003
  • Peer Reviewed
• [Journal Article] Anaphylactic reaction to dietary oats. (2013)
  • Author(s): Chisato Inuo
  • Journal Title: Ann Allergy Asthma Immunol. Volume: 110 Issue: 4 Pages: 305-306
  • DOI: 10.1016/j.anai.2013.01.008
  • Peer Reviewed
• [Journal Article] Food sensitization in Japanese infants is associated with a common Filaggrin variant. (2013)
  • Author(s): Nomura T, Tsuge I, Inuo C, Nakajima Y, Kondo Y, Sugiura S, Murata H, Iguchi T, Terada A, Saitoh S, Hashimoto S, Atsuo Urisu A.
  • Journal Title: Ann Allergy Asthma Immunol Volume: 110
  • Peer Reviewed
• [Journal Article] Japanese cedar-specific immunotherapy reduces allergen-specific Th2 cells in peripheral blood. (2013)
  • Author(s): Nomura T, Tsuge I, Inuo C, Nakajima Y, Tanaka K, Naruse N, Suzuki S, Ando H, Kondo Y, Saitoh S, Urisu A.
  • Journal Title: Ann Allergy Asthma Immunol Volume: 110
• [Journal Article] Acute eosinophilic pneumonia occurring in a dedicator of cytokinesis 8 (DOCK8 ) deficient patient. (2013)
  • Author(s): Tsuge I, Ito K, Ohye T, Kando N, Kondo Y, Nakajima Y, Inuo C, Kurahashi H, Urisu A.
  • Journal Title: Pediatr Pulmonol. Volume: 48
  • Peer Reviewed
• [Journal Article] New approach for improving the safety of oral immunotherapy for food allergy. (2012)
  • Author(s): Urisu A, Tanaka K, Ogura K, Naruse N, Hirata N, Nakajima Y, Inuo C, Suzuki S, Ando H, Kondo Y, Tsuge I, Yamada K, Kimura, M.
  • Journal Title: Clin Exp Allergy Rev Volume: 12 Issue: n2 Pages: 25-28
  • DOI: 10.1111/j.1472-9733.2012.01167.x
• [Journal Article] A patient with salmon roe allergy showing taxonomy-unrelated cross-reactivity with sea urchin roe (2011)
  • Author(s): Kondo Y, Tanaka K, Inuo C, Tsuge I, Urisu A.
  • Journal Title: Ann Allergy Asthma Immunol Volume: 107 Pages: 283-4
  • Peer Reviewed
• [Journal Article] Identification of FOXP3-negative regulatory T-like (CD4(+)CD25(+) CD127(low)) cells in patients with immune dysregulation, poly endocrinopathy, enteropathy, X-linked syndrome (2011)
  • Author(s): Otsubo K, Kanegane H, Kamachi Y, Kobayashi I, Tsuge I, Imaizumi M, Sasahara Y, Hayakawa A, Nozu K, Iijima K, Ito S, Horikawa R, Nagai Y, Takatsu K, Mori H, Ochs HD, Miyawaki T.
  • Journal Title: Clin Immunol Volume: 141 Pages: 111-20
  • Peer Reviewed
• [Journal Article] A patient with salmon roe allergy showing taxonomy-unrelated cross-reactivity with sea urchin roe. (2011)
  • Author(s): Kondo Y, Tanaka K, Inuo C, Tsuge I, Urisu A.
  • Journal Title: Ann Allergy Asthma Immunol. Volume: 107 Pages: 283-284
  • Peer Reviewed
• [Journal Article] Identification of FOXP3-negative regulatory T-like (CD4(+)CD25(+)CD127(low)) cells in patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. (2011)
  • Author(s): Otsubo K, Kanegane H, Kamachi Y, Kobayashi I, Tsuge I, Imaizumi M, Sasahara Y, Hayakawa A, Nozu K, Iijima K, Ito S, Horikawa R, Nagai Y, Takatsu K, Mori H, Ochs HD, Miyawaki T.
  • Journal Title: Clin Immunol. Volume: １４１ Pages: 111-120
  • Peer Reviewed
• [Journal Article] IL-10 signaling in hyper-IgE syndrome results in impaired generation of tolerogenic dendritic cells and induced regulatory T cells. (2011)
  • Author(s): Saito M, Nagasawa M, Takada H, Hara T, Tsuchiya S, Agematsu K, Yamada M, Kawamura N, Ariga T, Tsuge I, Nonoyama S, Karasuyama H, Minegishi Y.
  • Journal Title: J Exp Med. Volume: 208 Pages: 235-249
  • Peer Reviewed
• [Journal Article] 食物アレルギーに対する経口免疫療法の現状と将来 安全性と有効性の追求、当科での取り組みを含めて (2011)
  • Author(s): 柘植郁哉、宇理須厚雄
  • Journal Title: アレルギー・免疫 Volume: 18 Pages: 1118-1125
• [Journal Article] 経口免疫療法の今後の方向性 (2011)
  • Author(s): 柘植郁哉、宇理須厚雄
  • Journal Title: 臨床免疫・アレルギー科 Volume: 55 Pages: 651-656
• [Presentation] 食物アレルギー最前線皮膚粘膜バリア機能と食物アレルギー (2013)
  • Author(s): 柘植郁哉,野村孝泰,近藤康人,中島陽一,森雄司,大久保悠里子,田中健一,山脇一夫,成瀬徳彦,犬尾千聡,平田典子,鈴木聖子,高松伸枝,宇理須厚雄
  • Organizer: 第63回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2013-11-28
• [Presentation] 食物アレルギーの経口免疫療法オボムコイド減量加熱全卵を用いた経口免疫療法の免疫学的検討 (2013)
  • Author(s): 柘植郁哉,田中健一,野村孝泰,犬尾千聡,湯川牧子,高松伸枝,小倉和郎,成瀬徳彦,平田典子,鈴木聖子,安藤仁志,近藤康人,宇理須厚雄,山田一恵,小林幸子,木村守
  • Organizer: 第61回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2013-11-10
• [Presentation] 低アレルゲン化した鮭エキスを用いた魚アレルギーの経口免疫療法の試み (2013)
  • Author(s): 中島陽一、近藤康人、大久保悠里子、田中健一、山脇一夫、成瀬徳彦、犬尾千聡、平田典子、鈴木聖子、柘植郁哉、宇理須厚雄、高松伸枝、近藤智彦、中村厚、筬島克裕、板垣康治
  • Organizer: ,第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: 横浜
• [Presentation] スギ花粉症児の花粉シーズン暴露による末梢血好塩基球活性化の変化 (2013)
  • Author(s): 犬尾千聡、近藤康人、田中健一、中島陽一、山脇一夫、大久保悠里子、柘植郁哉、鈴木聖子、宇理須厚雄,
  • Organizer: 第25回日本アレルギー学会春季臨床大会
  • Place of Presentation: 横浜
• [Presentation] 卵白未摂取アトピー性皮膚炎児のオボムコイド減量ベビーフードに対するアレルギー反応誘発の検討 (2013)
  • Author(s): 森 雄司, 大久保 悠里子, 山脇 一夫, 田中 健一, 犬尾 千聡, 中島 陽一, 平田 典子, 鈴木 聖子, 近藤 康人, 柘植 郁哉, 木村 守, 宇理須 厚雄
  • Organizer: 第50回日本小児アレルギー学会
  • Place of Presentation: 横浜
• [Presentation] オボムコイド減量加熱卵白入りクッキーを用いた経口免疫療法実施例における現在の鶏卵摂取状況 (2013)
  • Author(s): 山田 一惠, 近藤 康人, 柘植 郁哉, 宇理須 厚雄, 木村 守
  • Organizer: 第50回日本小児アレルギー学会
  • Place of Presentation: 横浜
• [Presentation] 食物アレルギー最前線 皮膚粘膜バリア機能と食物アレルギー (2013)
  • Author(s): 柘植 郁哉, 野村 孝泰, 近藤 康人, 中島 陽一, 森 雄司, 大久保 悠里子, 田中 健一, 山脇 一夫, 成瀬 徳彦, 犬尾 千聡, 平田 典子, 鈴木 聖子, 高松 伸枝, 宇理須 厚雄
  • Organizer: 第63回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
• [Presentation] 活性化マーカーCD154を指標とした牛乳アレルギー患者の抗原特異的T細胞解析 (2012)
  • Author(s): 2） 野村孝泰、柘植郁哉、高松伸枝、田中健一、犬尾千聡、中島陽一、小倉和郎、成瀬徳彦、鈴木聖子、安藤仁志、近藤康人、宇理須厚雄,
  • Organizer: 第24回,日本アレルギー学会春季臨床大会
  • Place of Presentation: 大阪
• [Presentation] 低アレルゲン化した鮭エキスを用いた魚アレルギーの経口免疫療法を行った一例. (2012)
  • Author(s): 4） 中島陽一、近藤康人、大久保悠里子、田中健一、山脇一夫、成瀬徳彦、犬尾千聡、平田典子、鈴木聖子、柘植郁哉、宇理須厚雄、高松伸枝、筬島克裕、近藤智彦、板垣康治,
  • Organizer: 第62回,日本アレルギー学会秋季学術大会,
  • Place of Presentation: 大阪
• [Presentation] 食物（鶏卵、牛乳、小麦、）アレルギーに対する緩除漸増経口免疫療法の誘発反応の検討. (2012)
  • Author(s): 5） 成瀬徳彦、田中健一、平田典子、鈴木聖子、近藤康人、宇理須厚雄、大久保悠里子、山脇一夫、犬尾千聡、中島陽一、柘植郁哉、
  • Organizer: 第62回,日本アレルギー学会秋季学術大会,
  • Place of Presentation: 大阪
• [Presentation] オボムコイド減量加熱全卵を用いた経口免疫療法の免疫学的検討 (2011)
  • Author(s): 柘植郁哉,田中健一,野村孝泰,犬尾千聡,湯川牧子,近藤康人,成瀬徳彦,平田典子,鈴木聖子,小倉和郎,小松原亮,安藤仁志,高松伸枝,山田一恵,小林幸子,木村守,宇理須厚雄
  • Organizer: 第23回日本アレルギー学会春季臨床大会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-14
• [Presentation] 食物アレルギーの経口免疫療法 ;オボムコイド減量加熱全卵を用いた経口免疫療法の免疫学的検討 (2011)
  • Author(s): 柘植郁哉, 田中健一, 野村孝泰, 犬尾千聡, 湯川牧子, 高松伸枝, 小倉和郎, 成瀬徳彦, 平田典子, 鈴木聖子, 安藤仁志, 近藤康人, 宇理須厚雄, 山田一恵, 小林幸子, 木村守
  • Organizer: 第６１回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
• [Book] 食物アレルギーの経口免疫療法の適応について教えてください,アレルギー診療ガイドブック日本アレルギー学会編 (2012)
  • Author(s): 柘植郁哉
  • Total Pages: 433
  • Publisher: 診断と治療社
• [Book] 食物アレルギー,抗体開発ハンドブック浜窪隆雄監修 (2012)
  • Author(s): 柘植郁哉
  • Total Pages: 296
  • Publisher: エヌ・ティー・エス