Development of a new stem cell transplantation regimen in the treatment of refractory autoimmune diseases

• Project/Area Number: 21591266
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kyushu University
• Principal Investigator: TSUKAMOTO Hiroshi 九州大学, 大学病院, 助教 (70304772)
• Co-Investigator(Kenkyū-buntansha): HORIUCHI TAKAHIKO 九州大学, 医学研究院, 准教授 (90219212)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 造血幹細胞移植 / 自己免疫疾患 / CD34陽性細胞 / 免疫再構築 / 純化 / 造血幹細胞 / 移植 / 遺伝子発現プロファイル / 強皮症 / 制御性T細胞 / 間葉系幹細胞

Research Abstract

The objective was to determine the best regimen of autologous hematopoietic stem cell transplantation(auto-HSCT) for refractory autoimmune diseases. CD34+ selected auto-HSCT was more effective on skin sclerosis and more strongly associated with viral infection than unmanipulated auto-HSCT in patients with systemic sclerosis(SSc). The gene expression profile of lymphocytes more normalized in SSc patients who received CD34+ selected auto-HSCT than those who received unmanipulated auto-HSCT. In conclusion, CD34+ selected auto-HSCT should be applied in the treatment of refractory autoimmune diseases.

Research Products

• [Journal Article] CIN8s is required for Cbl-mediated regulation of antigen receptor signaling in human B cells (2012)
  • Author(s): Niiro H, JabbarzadehTabrizi S, Kikushige Y, Shima T, Neda K, eta S, Tsuzuki H, Inoue Y, Arinobu Y, Iwasaki H, Shimoda S, Baba E, Tsukamoto H, Horiuchi T, Taniyama T, and Akashi K.
  • Journal Title: Blood Volume: 119 Pages: 2263-2273
  • Peer Reviewed
• [Journal Article] CIN85 is required for Cbl-mediated regulation of antigen receptor signaling in human B cells (2012)
  • Author(s): Niiro H,…, Tsukamoto H, et al(16名中12番目)
  • Journal Title: Blood Volume: 119 Issue: 10 Pages: 2263-2273
  • DOI: 10.1182/blood-2011-04-351965
  • Peer Reviewed
• [Journal Article] Analysis of immune re constitution after autologous CD34+ stem/progenitor cell transplantation for systemic sclerosis (2011)
  • Author(s): Tsukamoto H, Nagafuji K, Horiuchi T, Mitoma H, Niiro H, Arinobu Y, Inoue Y, To K, Miyamoto T, Iwasaki H, Teshima T, Harada M, Akashi K.
  • Journal Title: predominant reconstitution of Th1 CD4+ T cells. Rheumatology Volume: 50 Pages: 944-52
  • Peer Reviewed
• [Journal Article] Prevalence of and risk factors for low bone mineral density in Japanese female patients with systemic lupus erythematosus (2011)
  • Author(s): Furukawa M, Kiyohara C, Tsukamoto H, Mitoma H, Kimoto Y, Uchino A, Nakagawa M, Oryoji K, Shimoda T, Akashi K, Harada M, Horiuchi T.
  • Journal Title: Rheumatol Int Volume: 31 Pages: 365-76
  • NAID: 120004951587
  • Peer Reviewed
• [Journal Article] Hereditary Angioedema in Japan : Genetic Analysis of 13 Unrelated Cases (2011)
  • Author(s): Yamamoto T, Horiuchi T, Miyahara H, Yoshizawa S, Maehara J, Shono E, Takamura K, Machida H, Tsujioka K, Kaneko T, Uemura N, Suzawa K, Inagaki N, Umegaki N, Kasamatsu Y, Hara A, Arinobu Y, Inoue Y, Niiro H, Kashiwagai Y, Harashima SI, Tahira T, Tsukamoto H
  • Journal Title: Am J Med Sci Volume: 342 Pages: 210-214
  • Peer Reviewed
• [Journal Article] Correlation between pretreatment or follow-up CT findings and therapeutic effect of autologous peripheral blood stem cell transplantation for interstitial pneumonia associated with systemic sclerosis (2011)
  • Author(s): Yabuuchi H, Matsuo Y, Tsukamoto H, Sunami S, Kamitani T, Sakai S, Hatakenaka M, Nagafuji K, Horiuchi T, Harada M, Akashi K, Honda H.
  • Journal Title: Eur J Radiol Volume: 79
  • Peer Reviewed
• [Journal Article] Analysis of immune reconstitution after autologous CD34+ stem/progenitor cell transplantation for systemic sclerosis : predominant reconstitution of Th1 CD4+ T cells (2011)
  • Author(s): Tsukamoto H, Nagafuji K, Horiuchi T, et al
  • Journal Title: Rheumatology Volume: 50 Pages: 944-952
  • Peer Reviewed
• [Journal Article] Correlation between pretreatment or follow-up CT findings and therapeutic effect of autologous peripheral blood stem cell transplantation for interstitial pneumonia associated with systemic sclerosis (2011)
  • Author(s): Yabuuchi H, Matsuo Y, Tsukamoto H, et al
  • Journal Title: Eur J Radiol Volume: 79 Issue: 2 Pages: e74-e79
  • DOI: 10.1016/j.ejrad.2011.03.078
  • Peer Reviewed
• [Journal Article] Tacrolimus is effective for lupus nephritis patients with persistent proteinuria (2010)
  • Author(s): Uchino A, Tsukamoto H, Nakashima H, Yoshizawa S, Furugo I, Mitoma H, Oryoji K, Shimoda T, Niiro H, Tada Y, Yano T, Nonaka T, Oishi R, Akashi K, Horiuchi T.
  • Journal Title: Clin Exp Rheumatol Volume: 28 Pages: 6-12
  • Peer Reviewed
• [Journal Article] Association of killer cell immunoglobulin-like receptoi 2DL5 with systemic lupus erythematosus and accompanying infections (2010)
  • Author(s): Kimoto Y, Horiuchi T, Tsukamoto H, Kiyohara C, Mitoma H, Uchino A, Furugo I, Yoshizawa S, Ueda A, Harashima S, Sawabe T, Tahira T, Hayashi K, Yoshizawa S, Shimoda T, Akashi K, Harada M.
  • Journal Title: Rheumatology Volume: 49 Pages: 1346-1353
  • Peer Reviewed
• [Journal Article] Association of killer cell immunoglobulin-like receptor 2DL5 with systemic lupus erythematosus and accompanying infections. (2010)
  • Author(s): Kimoto Y, Horiuchi T, Tsukamoto H, et al.
  • Journal Title: Rheumatology Volume: 49 Pages: 1346-53
  • Peer Reviewed
• [Journal Article] Tacrolimus is effective for lupus nephritis patients with persistent proteinuria. (2010)
  • Author(s): Uchino A, Tsukamoto H, Nakashima H, et al.
  • Journal Title: Clin Exp Rheumatol Volume: 28 Pages: 6-12
  • Peer Reviewed
• [Journal Article] Infectious complications in patients receiving autologous CD34selected hematopoietic stem cell transplantation for severe autoimmune diseases (2009)
  • Author(s): Kohno K, Nagafuji K, Tsukamoto H, Horiuchi T, Takase K, Aoki K, Henzan H, Kamezaki K, Takenaka K, Miyamoto T, Teshima T, Harada M, Akashi K.
  • Journal Title: Transpl Infect Dis Volume: 11 Pages: 318-323
  • Peer Reviewed
• [Journal Article] Kyushu Sapporo SLE Study Group. Combination of TNF-RII, CYP1A1 and GSTM1 polymorphisms and the risk of Japanese SLE : findings from the KYSS study (2009)
  • Author(s): Horiuchi T, Washio M, Kiyohara C, Tsukamoto H, Tada Y, Asami T, Ide S, Kobashi G, Takahashi H
  • Journal Title: Rheumatology Volume: 48 Pages: 1045-1049
  • Peer Reviewed
• [Journal Article] Infectious complications in patients receiving autologous CD34-selectedhematopoitic stem cell transplantation for severe autoimmune diseases (2009)
  • Author(s): Kohno K, Nagafuji K, Tsukamoto H, et al.
  • Journal Title: Transpl infect dis 11 Pages: 318-323
  • Peer Reviewed
• [Journal Article] Combination of TNF-RII, CYP1A1 and GSTM1 polymorphisms and risk of Japanese SLE : findings from the KYSS study (2009)
  • Author(s): Horiuchi T, Washio M, Kiyohara C, Tsukmaoto H, et al.
  • Journal Title: Rheumatology 48 Pages: 1045-1049
  • Peer Reviewed
• [Journal Article] Analysis of immune reconstitution after autologous CD34+ stem/progenitor cell transplantation for systemic sclerosis : predominant reconstitution of Th1 CD4+ T cells.
  • Author(s): Tsukamoto H, Nagafuji K, Horiuchi T, et al
  • Journal Title: Rheumatology Volume: (印刷中)
  • Peer Reviewed
• [Presentation] 全身性硬化症に対するCD34陽性細胞純化及び非純化自己造血幹細胞移植 (2011)
  • Author(s): 塚本浩、堀内孝彦、新納宏昭、他
  • Organizer: 第55回日本リウマチ学会総会
  • Place of Presentation: 神戸市
  • Year and Date: 2011-07-20
• [Presentation] CD34-selected and unmanipulated autologous hematopoietic stem cell transplantation for severe systemic sclerosis (2011)
  • Author(s): Tsukamoto H, Horiuchi T, Miyamoto T, et al
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: London, UK
  • Year and Date: 2011-05-27
• [Presentation] CD34-selected and unmanipulated autologous hematopoietic stem cell transplantation for severe systemic sclerosis (2011)
  • Author(s): Tsukamoto H, et al
  • Organizer: Annual European Congress of Rheumatology 2011
  • Place of Presentation: London,英国
  • Year and Date: 2011-05-27
• [Presentation] Autologous hematopoietic stem cell transplantation for severe systemic sclerosis (2010)
  • Author(s): Tsukamoto H, Horiuchi T, Miyamoto T, et al
  • Organizer: long-term follow-up analysis of immune reconstitution. Annual European Congress of Rheumatology
  • Place of Presentation: Rome. Italy
  • Year and Date: 2010-06-18
• [Presentation] 全身性硬化症に対する大量免疫抑制療法と自己造血幹細胞移植 (2010)
  • Author(s): 塚本浩、堀内孝彦、三苫弘喜、他
  • Organizer: 第54回日本リウマチ学会総会
  • Place of Presentation: 神戸市
  • Year and Date: 2010-04-24
• [Presentation] 全身性硬化症に対する大量免疫抑制療法と自己末梢血純化CD34陽性細胞移植:術後5年間の臨床成績と免疫学的検討 (2009)
  • Author(s): 塚本浩、堀内孝彦、三苫弘喜、他
  • Organizer: 第53回日本リウマチ学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-04-24
• [Presentation] 全身性硬化症に対する大量免疫抑制療法と非純化自己末梢血細胞移植の短期成績 (2009)
  • Author(s): 塚本浩、堀内孝彦、三苫弘喜、他
  • Organizer: 第53回日本リウマチ学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-04-24
• [Presentation] 全身性硬化症に対する大量免疫抑制療法と自己末梢血純化CD34陽性細胞移植:術後5年間の臨床成績と免疫学的検討 (2009)
  • Author(s): 塚本浩, 他
  • Organizer: 日本リウマチ学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-04-24
• [Book] 補体への招待 (2011)
  • Author(s): 大井洋之、木下タロウ、松下操、塚本浩堀内孝彦、他
  • Total Pages: 232
  • Publisher: メジカルレビュー社
• [Book] 補体への招待 (2011)
  • Author(s): 大井洋之, 木下タロウ, 松下操, 塚本浩, 他
  • Total Pages: 232
  • Publisher: メジカルレビュー社