Pathological analysis of acute graft-versus-host disease and development of molecular targeted therapy for acute GVHD

• Project/Area Number: 15K09657
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Sapporo Medical University
• Principal Investigator: Yamamoto Masaki 札幌医科大学, 医学部, 講師 (80404664)
• Co-Investigator(Kenkyū-buntansha): 堀 司 札幌医科大学, 医学部, 准教授 (20398324) ; 斉藤 淳人 札幌医科大学, 医学部, 研究員 (40749420) ; 五十嵐 敬太 札幌医科大学, 医学部, 助教 (70580017)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 移植片対宿主病 / ケモカイン / CCL8 / 急性移植片対宿主病 / バイオマーカー

Outline of Final Research Achievements

We performed mixed leukocyte reaction assay using wild type and CCL8-knockout mice. CCL8 protein were not detected in the supernatant of CCL8 KO mice. Also we preformed RNA interference assay with ccl8 specific siRNA. By the RNAi, CCL8 protein were slightly decreased in the supernatant. Thus, gene manipulation maybe the treatment option of acute GVHD
To explore the role of Chemokine (C-C motif) ligand 8 (CCL8) as a potential biomarker for acute graft-versus-host disease (aGVHD), we retrospectively analyzed the sera and clinical course of 31 patients with grade II to IV aGVHD. No deaths occurred in the ten patients with serum CCL8 concentrations less than 213 pg/mL, whereas 11 of the 21 patients with more than 213 pg/mL died within 180 days post-transplantation. Thus, elevated serum CCL8 concentration before day 100 post-transplantation may predict aGVHD prognosis.

Research Products

• [Journal Article] Early expression of serum CCL8 closely correlates to non-relapse mortality after allogeneic hematopoietic stem cell transplantation (2017)
  • Author(s): Masaki Yamamoto, Tsukasa Hori, Naoki Hatakeyama, Keita Igarashi, Natsuko Inazawa, Nobuhiro Suzuki, Norio Takei, Yoichi M. Ito, Kamikaze Matsumoto, Koji Kato, Hiroyuki Tsutsumi, Yasuo Kokai
  • Journal Title: 札幌医学雑誌 = The Sapporo Medical Journal Volume: 86 Issue: 1-6 Pages: 45-51
  • DOI: 10.15114/smj.86.45
  • NAID: 120006488957
  • ISSN: 0036-472X
  • URL: https://sapmed.repo.nii.ac.jp/records/16398
  • Peer Reviewed
• [Presentation] ケモカインCCL8の移植後早期発現は同種細胞移植における非再発死亡率の増加と相関する (2017)
  • Author(s): 山本 雅樹
  • Organizer: 第39回日本造血細胞移植学会総会
  • Place of Presentation: くにびきメッセ（島根県松江市）
  • Year and Date: 2017-03-02
• [Presentation] ケモカインCCL8の移植後早期発現は同種造血細胞移植における非再発死亡率の増加と相関する (2017)
  • Author(s): 山本雅樹, 堀 司、畠山直樹、五十嵐敬太、稲澤奈津子、鈴木信寛、武井則雄、伊藤陽一、松本公一、加藤剛二、堤裕幸、小海康夫
  • Organizer: 第39回日本造血細胞移植学会総会