Multilateral investigation on various antibodies aiming at realization of ABO incompatible and/or crossmatch positive lung transplantation

• Project/Area Number: 15K15516
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Respiratory surgery
• Research Institution: Kyoto University
• Principal Investigator: CHEN Fengshi 京都大学, 医学研究科, 講師 (00452334)
• Co-Investigator(Kenkyū-buntansha): 伊達 洋至 京都大学, 医学研究科, 教授 (60252962)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: HLA抗体 / 肺移植 / 血液型不適合 / 生体肺移植 / クロスマッチ陽性 / 血液型抗原 / 抗体関連型拒絶

Outline of Final Research Achievements

Recently, the importance of donor-specific anti-HLA antibodies (DSAs) has been pointed out in lung transplantation. We investigated various characteristics of DSAs in living-donor lobar lung transplantation (LDLLT) and cadaveric lung transplantation (CLT). Anti-HLA antibodies have been prospectively screened periodically in 134 patients undergoing lung transplantation. Anti-HLA antibodies were screened in 64 patients with LDLLT and 70 patients with CLT before and after lung transplantation. Postoperatively, 17 patients (13%) had de novo DSAs. There were 3 patients in LDLLT (5%) and 14 patients in CLT (20%, p=0.001). In LDLLT, DSAs vanished in 1 out of 3 patients, while, in CLT, DSAs were detected within 3 months postoperatively in 10 out of 14 patients (p=0.12). We confirmed that de novo DSAs were detected less frequently in LDLLT than in CLT.
Furthermore, we investigated chimerism of the lungs using injured lungs after hematopoieticstem cell transplantation.

Research Products

• [Journal Article] Significance of single lung transplantation in the currenct situation of severe door shortage in Japan. (2016)
  • Author(s): Miyoshi R, Chen-Yoshikawa TF, Hijiya K, Motoyama H, Aoyama A, Menju T, Sato T, Sonobe M, Date H.
  • Journal Title: Gen Thorac Cardiovasc Surg Volume: 64(2) Pages: 93-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Stenosis of the segmental bronchus is a characteristic airway complication in living-donor lobar lung transplantation. (2016)
  • Author(s): Miyamoto E. Chen-Yoshikawa TF, Higuchi H, Aoyama A, Date H.
  • Journal Title: J Heart Lung Transplant Volume: 35(3) Pages: 389-92
  • 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] Separate pulmonary venous anastomoses using a left atrial appendage in a left single lung transplantation. (2016)
  • Author(s): Chen-Yoshikawa TF, Goda Y, Dong L, Date H.
  • Journal Title: J Thorac Cardiovasc Surg Volume: 152(1)
  • 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] Pulmonary arterioplasty th end-to-end anastomosis of the lingular branch to the interpulmonary artery in living-donor lobectomy. (2016)
  • Author(s): Kayawake H, Chen-Yoshikawa TF, Aoyama A, Date H.
  • Journal Title: Ann Thorac Surg Volume: 102(4)
  • 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] Excellent outcome of donor lobectomy with various surgical techniques for the interlobar artery. (2016)
  • Author(s): Kayawake H, Chen-Yoshikawa TF, Aoyama A, Motoyama H, Hijiya K, Menju T, Sato T, Sonobe M, Date H.
  • Journal Title: Eur J Cardiothorac Surg Volume: -
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Protective effects of Imatinib on ischemia/reperfusion injury in rat lung. (2016)
  • Author(s): Tanaka S, Chen-Yoshikawa TF, Kajiwara M, Menju T, Ohata K, Takahashi M, Kondo T, Hijiya K, Motoyama H, Aoyama A, Masuda S, Date H.
  • Journal Title: Ann Thorac Surg Volume: 102(5) Pages: 1717-1724
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Malignancies after living-donor and cadaveric lung transplantation in Japanease patients. (2016)
  • Author(s): Tanaka S, Chen-Yoshikawa TF, Yamada T, Hijiya K, Motoyama H, Aoyama A, Date H.
  • Journal Title: Surg Today Volume: 46(12) Pages: 1415-19
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 血幹細胞移植後の肺障害による呼吸不全に対する肺移植 (2016)
  • Author(s): 陳豊史
  • Journal Title: 呼吸器疾患の最新医療」（株）寺田国際事務所／先端医療技術研究所 Volume: 46 Pages: 196-199
• [Journal Article] 肺移植における抗体関連型拒絶反応 (2015)
  • Author(s): 陳豊史、伊達洋至
  • Journal Title: 今日の移植 Volume: 28 Pages: 113-121
• [Journal Article] Postoperative Pulmonary Function and Complications in Living-donor Lobectomy. (2015)
  • Author(s): Chen F, Yamada T, Sato M, Aoyama A, Takahagi A, Menju T, Sato T, Sonobe M, Omasa M, Date H.
  • Journal Title: J Heart Lung Transplant. Volume: 34(8) Issue: 8 Pages: 1089-1094
  • DOI: 10.1016/j.healun.2015.03.016
  • Peer Reviewed / Open Access
• [Journal Article] Lung Allocation Score and Health-related Quality of Life in Japanese Candidates for Lung Transplantation. (2015)
  • Author(s): Chen F, Oga T, Yamada T, Sato M, Aoyama A, Chin K, Date H.
  • Journal Title: Interact Cardiovasc Thorac Surg. Volume: 21(1) Issue: 1 Pages: 28-33
  • DOI: 10.1093/icvts/ivv101
  • Peer Reviewed / Open Access
• [Journal Article] Imatinib for sclerodermatous graft-versus-host disease in lung transplantation. (2015)
  • Author(s): Zhang J, Chen F, Ueki T, Date H.
  • Journal Title: Interact Cardiovasc Thorac Surg. Volume: 21(2) Issue: 2 Pages: 260-262
  • DOI: 10.1093/icvts/ivv122
  • Peer Reviewed / Open Access
• [Presentation] 肺移植における組織適合性検査の現状と今後 (2016)
  • Author(s): 陳 豊史、濱路政嗣、土屋恭子、本山秀樹、青山晃博、伊達洋至
  • Organizer: 第52回日本移植学会総会
  • Place of Presentation: 東京
• [Presentation] 肺移植におけるchronic lung allograft dysfuncion (CLAD)の検討 (2016)
  • Author(s): 陳 豊史、濱路政嗣、土屋恭子、本山秀樹、青山晃博、糀谷康子、磯見真希、伊達洋至。
  • Organizer: 第52回日本移植学会総会
  • Place of Presentation: 東京
• [Presentation] 肺移植の基礎から応用：現場から学べること (2016)
  • Author(s): 陳 豊史
  • Organizer: 第22回呼吸器外科セミナー
  • Place of Presentation: 京都
• [Presentation] 交差反応抗原群（CREG）による抗体関連拒絶が疑われた脳死片肺移植の1例。 (2016)
  • Author(s): 合地史明、陳 豊史、岡部 亮、山岸弘哉、高萩亮宏、齊藤正男、大畑惠資、濱路政嗣、土屋恭子、本山秀樹、青山晃博、伊達洋至
  • Organizer: 第25回日本組織適合性学会大会
  • Place of Presentation: 札幌
• [Presentation] 肺移植におけるドナー特異的抗体についての検討。 (2016)
  • Author(s): 陳 豊史、合地史明、岡部 亮、山岸弘哉、高萩亮宏、齊藤正男、大畑惠資、土屋恭子、本山秀樹、青山晃博、万木紀美子、菱田理恵、前川 平、伊達洋至
  • Organizer: 第25回日本組織適合性学会大会
  • Place of Presentation: 札幌
• [Presentation] 本邦における造血幹細胞移植後の肺移植の検討 (2016)
  • Author(s): 陳 豊史、杉本誠一郎、白石武史、南正人、松田安史、千田雅之、前田寿美子、青山晃博、岡田克典、奥村明之進、岩崎昭憲、三好新一郎、大藤剛宏、伊達洋至
  • Organizer: 第52回日本移植学会総会
  • Place of Presentation: 東京
• [Presentation] Comparison of De Novo Donor-Specific Anti-HLA Antibodies (DSAs) Between Living-Donor Lobar Lung Transplantation and Cadaveric Lung Transplantation. (2016)
  • Author(s): Toyofumi F. Chen-Yoshikawa, Takeshi Kondo, Akihiro Ohsumi, Masao Saito, Akihiro Takahagi, Satona Tanaka, Ei Miyamoto, Mamoru Takahashi, Keiji Ohata, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hiroshi Date
  • Organizer: 36th Annual Meeting of the International Society for Heart and Lung Transplantation
  • Place of Presentation: Washington DC,USA
• [Presentation] Insufficient post-transplant immunosuppression induces restrictive allograft symdrome-like fibrosis in the pleura and lung parenchyma after lung transplantation. (2016)
  • Author(s): Miyamoto E, Sato M, Motoyama H, Aoyama A, Menju T, Shikuma K, Sowa T, Saito M, Takahagi A, Tanaka S, Takahashi M, Ohata K, Kondo T, Hijiya K, Toyofumi F. Chen-Yoshikawa, Sato T, Sonobe M, Date H.
  • Organizer: 36th Annual Meeting of the International Society for Heart and Lung Transplantation
  • Place of Presentation: Washington DC,USA
• [Presentation] 生体肺移植と脳死肺移植におけるHLA mismatchとドナー特異抗体の検討。 (2015)
  • Author(s): １．近藤健、陳 豊史、高萩亮宏、齊藤正男、田中里奈、宮本英、高橋守、大畑惠資、土屋恭子、本山秀樹、青山晃博、伊達洋至
  • Organizer: 第51回日本移植学会
  • Place of Presentation: 熊本市,熊本
  • Year and Date: 2015-10-02
• [Presentation] 生体肺移植と脳死肺移植におけるドナー特異的抗体の相違についての検討。 (2015)
  • Author(s): ２．陳 豊史、近藤 健、高萩亮宏、齊藤正男、田中里奈、宮本英、高橋 守、大畑恵資、土屋恭子、本山秀樹、青山晃博、伊達洋至
  • Organizer: 第23回日本組織適合性学会大会
  • Place of Presentation: 水戸市,茨城
  • Year and Date: 2015-09-10
• [Presentation] Characteristics of de novo donor-specific anti-HLA antibodies (DSAs) in living-donor lobar lung transplantation might be different from those in cadaveric lung transplantation. (2015)
  • Author(s): ３．Kondo T, Chen F, Ohsumi A, Takahashi M, Ohata K, Hijiya K, Motoyama H, Tanaka S, Miyamoto E, Yamada T, Sato M, Aoyama A, Date H.
  • Organizer: 35th Annual Meeting of the International Society for Heart and Lung Transplantation
  • Place of Presentation: Nice,France
  • Year and Date: 2015-04-15
• [Book] 第XIII章 肺移植 ６．術後合併症 日本呼吸器外科学会 呼吸器外科専門医合同委員会 編集 呼吸器外科テキスト (2016)
  • Author(s): 陳 豊史
  • Publisher: 南江堂
• [Remarks] 京都大学 呼吸器外科
  • URL: http://www.thoracic-kyoto-u.gr.jp