Establishment of experimental and clinical evidences for a link between tonsillar focal diseases and palatine tonsil

• Project/Area Number: 17K11372
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Asahikawa Medical College
• Principal Investigator: Takahara Miki 旭川医科大学, 医学部, 講師 (50322904)
• Co-Investigator(Kenkyū-buntansha): 長門 利純 旭川医科大学, 医学部, 講師 (80431419)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 扁桃病巣疾患 / 掌蹠膿疱症 / IgA腎症 / APRIL / CX3CR1 / 扁桃摘出術 / 口蓋扁桃

Outline of Final Research Achievements

Palmoplantar pustulosis (PPP) and IgA nephropathy (IgAN) are known as typical tonsillar focal diseases, and tonsillectomy has been reported to be effective for improvement of the symptoms and findings. Unfortunately, this disease concept was not widely known. We try to establish experimental and clinical evidence for a link between tonsillar focal diseases and palatine tonsil, and enlighten other doctors on the concept. In this serious of studies, we showed the effectiveness of tonsillectomy for PPP skin lesions by objective evaluation. Moreover, we found that APRIL (a proliferation-inducing ligand) was involved in hyper-production of IgA from the IgAN patients tonsils, and that chemokine receptor CX3CR1 was related to homing of tonsillar T-cells to the lesions of glomerulus.

Academic Significance and Societal Importance of the Research Achievements

学術的意義として今まで主観的評価が主だった掌蹠膿疱症の扁摘効果が客観的にも示された。またIgA腎症と扁桃を結びつける基礎的根拠が液性免疫、細胞性免疫両面から示された。社会的意義としてこれらの研究結果の発表や報告を読んで、本疾患群に興味を持ち、概念を理解する医師が増加する可能性がある。更には適応患者の耳鼻咽喉科への紹介、耳鼻咽喉科での手術、その結果、疾患から解放される患者が増加する可能性が示された。

Research Products

• [Journal Article] 扁桃病巣感染症、慢性扁桃炎が疑われる場足の問診のポイント (2020)
  • Author(s): 高原 幹
  • Journal Title: MB ENT Volume: 244 Pages: 113-117
• [Journal Article] A proliferation-inducing ligand (APRIL) induced hyper-production of IgA from tonsillar mononuclear cells in patients with IgA nephropathy (2019)
  • Author(s): Takahara Miki、Nagato Toshihiro、Nozaki Yui、Kumai Takumi、Katada Akihiro、Hayashi Tatsuya、Harabuchi Yasuaki
  • Journal Title: Cellular Immunology Volume: 341 Pages: 103925-103925
  • DOI: 10.1016/j.cellimm.2019.103925
  • Peer Reviewed / Open Access
• [Journal Article] Pathogenic role of palatine tonsils in palmoplantar pustulosis: A review (2019)
  • Author(s): Harabuchi Yasuaki、Takahara Miki
  • Journal Title: The Journal of Dermatology Volume: 46 Issue: 11 Pages: 931-939
  • DOI: 10.1111/1346-8138.15100
  • Peer Reviewed
• [Journal Article] 扁桃病巣疾患 (2019)
  • Author(s): 高原 幹
  • Journal Title: Current Decision Support Volume: -
• [Journal Article] Recent advances in the immunological understanding of association between tonsil and immunoglobulin A nephropathy as a tonsil-induced autoimmune/inflammatory syndrome. (2019)
  • Author(s): Harabuchi Y, Takahara M.
  • Journal Title: Immun Inflamm Dis. Volume: 7 Issue: 2 Pages: 86-93
  • DOI: 10.1002/iid3.248
  • Peer Reviewed / Open Access
• [Journal Article] 【小児の反復性症例にどう対応するか】 小児の反復する咽頭・扁桃炎にどう対応するか 反復性扁桃炎 vs. PFAPA (2019)
  • Author(s): 高原幹
  • Journal Title: ENTONI (1346-2067) Volume: 227 Pages: 43-46
  • Peer Reviewed
• [Journal Article] Treatment outcome and prognostic factors of tonsillectomy for palmoplantar pustulosis and pustulotic arthro-osteitis: A retrospective subjective and objective quantitative analysis of 138 patients. (2018)
  • Author(s): Takahara M, el al
  • Journal Title: J Dermatol Volume: 45 Issue: 7 Pages: 812-823
  • DOI: 10.1111/1346-8138.14348
  • NAID: 120006714614
  • Peer Reviewed
• [Journal Article] Up-regulation of CX3CR1 on tonsillar CD8 T-cells in patients with IgA nephropathy (2017)
  • Author(s): Otaka R, Takahara M, Ueda S, Nagato T, Kishibe K, Nomura K, Katada A, Hayashi T, Harabuchi Y
  • Journal Title: Hum Immunol. Volume: 78 Issue: 4 Pages: 375-383
  • DOI: 10.1016/j.humimm.2017.02.004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 扁桃病巣疾患:IgA腎症 (2017)
  • Author(s): 高原 幹
  • Journal Title: 耳鼻免疫アレルギー Volume: 35 Pages: 7-10
  • NAID: 130005475647
  • Peer Reviewed
• [Presentation] 教育セミナー３ 扁桃病巣疾患の最近のトピックス (2019)
  • Author(s): 高原幹
  • Organizer: 第32回 日本口腔・咽頭科学会総会ならびに学術講演会
  • Invited
• [Presentation] 胸肋鎖骨過形成症における扁桃摘出術の効果 (2019)
  • Author(s): 高原幹
  • Organizer: 第120回 日本耳鼻咽喉科学会総会・学術講演会
• [Presentation] 掌蹠膿疱症、乾癬、アナフィラクトイド紫斑病における扁桃摘出術の効果 (2018)
  • Author(s): 高原幹
  • Organizer: 第26回旭川皮膚免疫研究会 （3.30, 2018, 旭川）
  • Invited
• [Presentation] 耳鼻科医から見る掌蹠膿疱症と扁桃摘出術の適応 (2018)
  • Author(s): 高原幹
  • Organizer: 第82回日本皮膚科学会東部支部学術大会
  • Invited
• [Presentation] 掌蹠膿疱症に対する扁桃摘出術の客観的評価と予後因子の検討 (2017)
  • Author(s): 高原 幹、他
  • Organizer: 日本耳鼻咽喉科学会総会・学術講演会
• [Presentation] IgA腎症扁桃におけるCX3CR1の検討 (2017)
  • Author(s): 高原 幹、他
  • Organizer: 日本腎臓学会学術総会
• [Presentation] Objective evaluation for improvement of skin lesion in patients with Pustulosis palmaris et plantaris (PPP) after tonsillectomy (2017)
  • Author(s): Miki Takahara, et al
  • Organizer: ENT World Congress Paris 2017
  • Int'l Joint Research
• [Presentation] 掌蹠膿疱症、乾癬における扁桃摘出術の効果 (2017)
  • Author(s): 高原 幹
  • Organizer: 旭川皮膚免疫研究会
  • Invited
• [Book] IgA腎症の病態と治療 (2019)
  • Author(s): 富野 康日己、川村 哲也、鈴木 祐介
  • Total Pages: 317
  • Publisher: 中外医学社
  • ISBN: 9784498224469
• [Remarks] 旭川医科大学 耳鼻咽喉科・頭頸部外科 研究概要
  • URL: http://www.asahikawa-med.ac.jp/dept/mc/oto/contents/study.html
• [Remarks] 旭川医科大学 耳鼻咽喉科・頭頸部外科 研究概要
  • URL: http://www.asahikawa-med.ac.jp/dept/mc/oto/contents/study.html