Early diagnosis and novel treatment with low-dose IL-2 of humoral rejection in lung transplantation.

• Project/Area Number: 15K10253
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Kyoto University
• Principal Investigator: Aoyama Akihiro 京都大学, 医学研究科, 講師 (60379047)
• Co-Investigator(Kenkyū-buntansha): 陳 豊史 京都大学, 医学研究科, 講師 (00452334) ; 伊達 洋至 京都大学, 医学研究科, 教授 (60252962)
• Research Collaborator: Kawai Tatsuo ハーバード大学, 医学部, 教授
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肺移植 / 抗体 / 慢性拒絶反応 / 制御性T細胞 / 慢性拒絶 / 免疫抑制 / ラット

Outline of Final Research Achievements

Study 1: 193 lung transplantations (LuTx) was performed and 146 patients were alive s of March 2018. Anti-donor antibody was detected in peripheral blood in 20 cases. During the study period, nine patients developed obstructive bronchiolitis, and except one autopsy and one retransplantation, pulmonary biopsy was impossible due to poor status of the patients.
Study 2: Rat orthotopic LuTx model was established, which is closer to clinical lung transplant than tracheal transplantation. Using this model, administration of 14-day cyclosporine resulted in anti-donor antibody in lung tissue and histologically obstructive bronchiolitis. It was confirmed that antibody production in lung allograft was produced in rat lung transplantation model.

Research Products

• [Journal Article] Association of Local Intrapulmonary Production of Antibodies Specific to Donor Major Histocompatibility Complex Class I with the Progression of Chronic Rejection of Lung Allografts. (2017)
  • Author(s): Miyamoto E, Motoyama H, Sato M, Aoyama A, Menju T, Shikuma K, Sowa T, Yoshizawa A, Saito M, Takahagi A, Tanaka S, Takahashi M, Ohata K, Kondo T, Hijiya K, Chen-Yoshikawa TF, Date H.
  • Journal Title: Transplantation Volume: 印刷中 Issue: 5 Pages: e156-e165
  • DOI: 10.1097/tp.0000000000001665
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of Toll-like recetor 4 signaling ameliorates lung ischemia-reperfusion injury in acute hyperglycemic conditions. (2016)
  • Author(s): Takahashi M, Chen-Yoshikawa TF, Menju T, Ohata K, Kondo T, Motoyama H, Hijiya K, Aoyama A, Date H.
  • Journal Title: J Heart Lung Transplant Volume: 35(6) Pages: 815-22
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Vascular endothelial-cadherin expression after reperfusion correlates with lung injury in rat lung transplantation. (2016)
  • Author(s): Tanaka S, Chen-Yoshikawa TF, Miyamoto E, Takahashi M, Ohata K, Kondo T, Hijiya K, Motoyama H, Aoyama A, Date H.
  • Journal Title: Ann Thorac Surg Volume: 101(6) Pages: 2161-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Bronchodilator inhalation during ex vivo lung perfusion improves posttransplant graft function after warm ischemia. (2016)
  • Author(s): Hijiya K, Chen-Yoshikawa TF, Kondo T, Motoyama H, Ohsumi A, Nakajima D, Sakamoto J, Ohata K, Takahashi M, Tanaka S, Miyamoto E, Aoyama A, Date H.
  • Journal Title: Ann Thorac Surg Volume: -
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Protective effect of inhaled Rho-kinase inhibitor on lung ischemia-reperfusion injury. (2016)
  • Author(s): Ohata K, Chen-Yoshikawa TF, Menju T, Miyamoto E, Tanaka S, Takahashi M, Motoyama H, Hijiya K, Aoyama A, Date H.
  • Journal Title: Ann Thorac Surg Volume: -
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Right-to-left inverted living-donor lobar lung transplantation combined with sparing of native upper lobe. (2016)
  • Author(s): 452.Goda Y, Motoyama H, Aoyama A, Hamaji M, Hijiya K, Chen-Yoshikawa TF, Date H.
  • Journal Title: J Heart Lung Transplant Volume: -
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Unilateral chronic lung allograft dysfunction is a characteristic of bilateral living-donor lobar lung transplantation. (2015)
  • Author(s): 41.Miyamoto E, Chen F, Aoyama A, Sato M, Yamada T, Date H.
  • Journal Title: Eur J Cardiothorac Surg Volume: 48 Pages: 463-469
  • Peer Reviewed
• [Presentation] Airway-Centered Inflammation Induced by Lipopolysaccharide Leads to BOS-Like Phenotype of CLAD in Rat Lung Transplantation (2017)
  • Author(s): Akihiro TAKAHAGI
  • Organizer: International Society for Heart and Lung Transplantation
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2017-04-05
  • Int'l Joint Research
• [Presentation] ラット同所性肺移植モデルにおけるRestrictive Allograft Syndrome類似肺障害：移 植肺障害多様性の検討 (2016)
  • Author(s): 宮本 英、佐藤 雅昭、本山 秀樹、青山 晃博、齊藤 正男、高萩 亮宏、田中 里奈、高橋 守、 大畑 恵資、土屋 恭子、近藤 健、陳 豊史、伊達 洋至
  • Organizer: 第32回日本肺および心肺移植研究会
  • Place of Presentation: 日光、栃木
  • Year and Date: 2016-01-30
• [Remarks] 京都大学呼吸器外科
  • URL: https://www.thoracic-kyoto-u.gr.jp/
• [Remarks] 京都大学呼吸器外科
  • URL: http://www.thoracic-kyoto-u.gr.jp