Acid-induced innate immune response in pathogenesis of eosinophilic esophagitis

• Project/Area Number: 18K07917
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Osaka City University
• Principal Investigator: Yasuhiro Fujiwara 大阪市立大学, 大学院医学研究科, 教授 (40285292)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 好酸球性食道炎 / 好酸球性消化管疾患 / IgE / プロトンポンプ阻害薬 / カリウム競合型アシッドブロッカー / 内視鏡 / バレット食道 / 食道裂孔ヘルニア

Outline of Final Research Achievements

We performed basic and clinical studies about eosinophilic esophagitis (EoE), and obtained the following research results: 1) IgE-mediated allergic sensitization patterns are associated with clinical features of patients with EoE. 2) Patients with asymptomatic EoE have similar histopathological esophageal inflammation. 3) Obesity and hiatal hernia may be non-allergic risk factors for EoE. 4) Barrett’s esophagus is negatively associated with EoE in Japanese subjects. 5) Presence of reflux esophagitis and absence of rings on endoscopy especially during GI screening, and localized EoE might be significant predictive factors for PPI response. 6) Vonoprazan showed similar efficacy to PPIs in EoE. 7) Several unique endoscopic findings of gastric lesions were observed in patients with gastric lesions of EGID. 8) Japanese data of EoE were reviewed and current therapeutic strategy of EoE, and ultimately proposes symptom-based diagnostic approach for EoE.

Academic Significance and Societal Importance of the Research Achievements

指定難病である好酸球性食道の病態、診断、治療について検討した。特に本邦における本疾患の現況を解明できたことは、病態解明と今後の診療に寄与する。一部の研究成果は国際的にも通用するものであり、国内外の関連学会において高い評価を得ている。

Research Products

• [Journal Article] Vonoprazan shows efficacy similar to that of proton pump inhibitors with respect to symptomatic, endoscopic, and histological responses in patients with eosinophilic esophagitis. (2021)
  • Author(s): Kuzumoto T, Tanaka F, Sawada A, Nadatani Y, Otani K, Hosomi S, Kamata N, Taira K, Nagami Y, Tanigawa T, Watanabe T, Fujiwara Y.
  • Journal Title: Esophagus Volume: 18 Issue: 2 Pages: 372-379
  • DOI: 10.1007/s10388-020-00783-0
  • NAID: 120007153301
  • Peer Reviewed
• [Journal Article] Classification of patients with esophageal eosinophilia by patterns of sensitization revealed by a diagnostic assay for multiple allergen-specific IgEs. (2021)
  • Author(s): Nakata A, Tanaka F, Nadatani Y, Fukunaga S, Otani K, Hosomi S, Kamata N, Taira K, Nagami Y, Watanabe T, Fujiwara Y.
  • Journal Title: J Gastroenterol. Volume: - Issue: 5 Pages: 422-433
  • DOI: 10.1007/s00535-021-01766-3
  • Peer Reviewed
• [Journal Article] Symptom-based diagnostic approach for eosinophilic esophagitis. (2020)
  • Author(s): Fujiwara Y.
  • Journal Title: J Gastroenterol. Volume: 55 Issue: 9 Pages: 833-845
  • DOI: 10.1007/s00535-020-01701-y
  • Peer Reviewed / Open Access
• [Journal Article] Endoscopic findings of gastric lesions in patients with eosinophilic gastrointestinal disorders. (2020)
  • Author(s): Fujiwara Y, Tanoue K, Higashimori A, Nishida Y, Maruyama M, Itani S, Ominami M, Nadatani Y, Fukunaga S, Otani K, Hosomi S, Tanaka F, Kamata N, Nagami Y, Taira K, Machida H, Tanigawa T, Watanabe T, Ohsawa M; F-Study group.
  • Journal Title: Endosc Int Open. Volume: 8 Issue: 12 Pages: E1817-E1825
  • DOI: 10.1055/a-1268-7312
  • Peer Reviewed / Open Access
• [Journal Article] Association between endoscopic findings of eosinophilic esophagitis and responsiveness to proton pump inhibitors. (2019)
  • Author(s): Sawada A, Hashimoto A, Uemura R, Otani K, Tanaka F, Nagami Y, Yamagami H, Tanigawa T, Watanabe T, Fujiwara Y.
  • Journal Title: Endosc Int Open. Volume: 7 Issue: 04 Pages: E433-E439
  • DOI: 10.1055/a-0859-7276
  • Peer Reviewed / Open Access
• [Journal Article] Obesity and hiatal hernia may be non-allergic risk factors for esophageal eosinophilia in Japanese adults. (2019)
  • Author(s): Tanaka F, Fukumoto S, Morisaki T, Otani K, Hosomi S, Nagami Y, Kamata N, Taira K, Nakano A, Kimura T, Yamagami H, Tanigawa T, Morikawa H, Watanabe T, Kawada N, Hirata K, Fujiwara Y.
  • Journal Title: Esophagus Volume: 16 Issue: 3 Pages: 309-315
  • DOI: 10.1007/s10388-019-00662-3
  • NAID: 120006876362
  • Peer Reviewed
• [Journal Article] Barrett's esophagus is negatively associated with eosinophilic esophagitis in Japanese subjects. (2019)
  • Author(s): Takashima S, Tanaka F, Otani K, Hosomi S, Nagami Y, Kamata N, Taira K, Yamagami H, Tanigawa T, Fukumoto S, Watanabe T, Fujiwara Y.
  • Journal Title: Esophagus Volume: 16 Issue: 2 Pages: 168-173
  • DOI: 10.1007/s10388-018-0648-2
  • NAID: 40021862180
  • Peer Reviewed
• [Journal Article] Optimal Biopsy Protocol to Evaluate Histological Effectiveness of Proton Pump Inhibitor Therapy in Patients with Eosinophilic Esophagitis (2018)
  • Author(s): Fujiwara Yasuhiro、Hashimoto Atsushi、Uemura Risa、Sawada Akinari?、Otani Koji、Tanaka Fumio、Yamagami Hirokazu、Tanigawa Tetsuya、Watanabe Toshio、Kabata Daijiro、Kuwae Yuko、Shintani Ayumi、Ohsawa Masahiko
  • Journal Title: Digestion Volume: 11 Issue: 1 Pages: 1-8
  • DOI: 10.1159/000494253
  • Peer Reviewed
• [Presentation] 好酸球性胃炎の内視鏡像の特徴についての検討 (2020)
  • Author(s): 藤原靖弘 小阪聡 田中史生
  • Organizer: JDDW2020
• [Presentation] VONOPRAZAN SHOWS EFFICACY SIMILAR TO THAT OF PRPTON PUMP INHIBITORS WITH RESPECT TO SYMPTOMATIC, ENDOSCOPIC, HISTOLOGICAL RESPONSES AMONG EOSINOPHILIC ESOPHAGITIS PATIENTS (2019)
  • Author(s): Y Fujiwara et al.
  • Organizer: DDW
  • Int'l Joint Research
• [Presentation] PPI反応性好酸球性食道炎における自覚症状、内視鏡像、組織所見の改善度についての検討 (2019)
  • Author(s): 藤原靖弘、橋本篤、上村理沙、沢田明也、大谷恒史、田中史生、山上博一、谷川徹也、渡邉俊雄
  • Organizer: 第15回日本消化管学会総会学術集会
• [Presentation] PPI治療後における好酸球性食道炎診断のための至適な生検方法に関する検討 (2018)
  • Author(s): 藤原靖弘、橋本篤、上村理沙
  • Organizer: JDDW2018