Development of a novel therapeutic strategy targeting CD38+CD43+ B cell for SLE based on gene expression profile

• Project/Area Number: 15K09515
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Tohoku University
• Principal Investigator: FUJII HIROSHI 東北大学, 医学系研究科, 准教授 (30531321)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 全身性エリテマトーデス / インターフェロンα / B細胞 / 形質芽細胞 / 自己抗体

Outline of Final Research Achievements

We tried to develop the novel therapeutic strategy for SLE by analysis of gene expression profiling of plasmablast, naive B cell, memory B cell from healthy donors and SLE patients. Whereas IFN inducible genes were significantly elevated in each B cell subset of SLE patients, cell cycle related genes were increased in SLE plasmablast. And we also showed that priming of B cell with IFNα stimulation caused to lower the threshold for B cell stimulation.

Research Products

• [Journal Article] Successful Cord Blood Stem Cell Transplantation for Primary Cutaneous CD8-positive Aggressive Epidermotropic Cytotoxic T-cell Lymphoma Complicated with Cerebral Infiltration (2018)
  • Author(s): Ichikawa S, Fukuhara N, Hatta S, Himuro M, Katsushima H, Nasu K, Ono K, Inokura K, Kobayashi M, Onishi Y, Fujii H, Ishizawa K, Ichinohasama R, Harigae H.
  • Journal Title: Internal Medicine Volume: 57 Issue: 14 Pages: 2051-2055
  • DOI: 10.2169/internalmedicine.0568-17
  • NAID: 130007404899
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-07-15
  • Peer Reviewed / Open Access
• [Journal Article] Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis (AAV) Restricted to the Limbs (2018)
  • Author(s): Ojima Y, Sawada K, Fujii H, Shirai T, Saito A, Kagaya S, Aoki S, Takeuchi Y, Ishii T, Nagasawa T.
  • Journal Title: Internal Medicine Volume: 57 Issue: 9 Pages: 1301-1308
  • DOI: 10.2169/internalmedicine.9848-17
  • NAID: 130006730798
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-05-01
  • Peer Reviewed / Open Access
• [Journal Article] Multicenter double-blind randomized controlled trial to evaluate the effectiveness and safety of bortezomib as a treatment for refractory systemic lupus erythematosus. (2018)
  • Author(s): Ishii T, Tanaka Y, Kawakami A, Saito K, Ichinose K, Fujii H, Shirota Y, Shirai T, Fujita Y, Watanabe R, Chiu SW, Yamaguchi T, Harigae H.
  • Journal Title: Modern Rheumatology Volume: - Issue: 6 Pages: 1-7
  • DOI: 10.1080/14397595.2018.1432331
  • Peer Reviewed / Open Access
• [Journal Article] Bortezomib treatment induces a higher mortality rate in lupus model mice with a higher disease activity. (2017)
  • Author(s): Ikeda T, Fujii H, Nose M, Kamogawa Y, Shirai T, Shirota Y, Ishii T, Harigae H.
  • Journal Title: Arthritis Research & Therapy Volume: 19（1） Issue: 1 Pages: 187-187
  • DOI: 10.1186/s13075-017-1397-7
  • Peer Reviewed / Open Access
• [Journal Article] Relapsing Polychondritis Complicated by Myelodysplastic Syndrome Is Resistant to Immunosuppression: Comment on the Article by Dion et al. (2017)
  • Author(s): Shirai T, Fujii H, Saito R, Nasu K, Kamogawa Y, Fukuhara N, Fujita Y, Shirota Y, Ishii T, Harigae H.
  • Journal Title: Arthritis & Rheumatology Volume: 69 Issue: 3 Pages: 682-683
  • DOI: 10.1002/art.39969
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tolerogenic immunoreceptor ILT3/LILRB4 paradoxically marks pathogenic auto-antibody-producing plasmablasts and plasma cells in non-treated SLE. (2016)
  • Author(s): Inui M, Sugahara-Tobinai A, Fujii H, Itoh-Nakadai A, Fukuyama H, Kurosaki T, Ishii T, Harigae H, Takai T.
  • Journal Title: International Immunology Volume: 28 Issue: 3 Pages: 597-604
  • DOI: 10.3109/14397595.2015.1012797
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Human CD43+ B cells are closely related not only to memory B cells phenotypically but also to plasmablasts developmentally in healthy individuals. (2015)
  • Author(s): Inui M, Hirota S, Hirano K, Fujii H, Sugahara-Tobinai A, Ishii T, Harigae H, Takai T
  • Journal Title: Internationa Immunology Volume: 27 Issue: 7 Pages: 345-55
  • DOI: 10.1093/intimm/dxv009
  • Peer Reviewed / Open Access
• [Presentation] 高疾患活動性ループスモデルマウスへのボルテゾミブ投与による致死的毒性について (2017)
  • Author(s): 藤井博司、能勢眞人、武藤智之、秋田佳奈恵、鴨川由起子、白井剛志、城田祐子、石井智徳、張替秀郎
  • Organizer: 第61回日本リウマチ学会総会・学術集会
• [Presentation] Bortezomib Treatment Induces Higher Mortality Rate in Lupus Model Mice with High Disease Activity (2016)
  • Author(s): Hiroshi Fujii, Tomoko Ikeda, Masao Nose, Tomoyuki Muto, Kanae Akita, Yukiko Kamogawa, Tsuyoshi Shirai, Tomonori Ishii, Hideo Harigae
  • Organizer: 2016ACR Annual Meeting
  • Place of Presentation: Walter E. Washington Convention Center (USA)
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] Longer suppression of anti deDNA antibody by sequential therapy with bortezomib and cyclophosphamide in lupus model mouse (2016)
  • Author(s): 藤井博司、能勢眞人、武藤智之、秋田佳奈恵、鴨川由起子、藤田洋子、城田祐子、石井智徳、張替秀郎
  • Organizer: 第60回日本リウマチ学会総会・学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-04-22
• [Presentation] Cell cycle related gene signature and interferon inducible gene signature in circulating CD38+CD43+ B cell subset in B cell (2015)
  • Author(s): Hiroshi Fujii, Tomoaki Machiyama, Kanae Akita, Yukiko Kamogawa, Ryu Watanabe, Yoko Fujita, Yuko Shirota, Tomonori Ishii, Hideo Harigae
  • Organizer: 第59回日本リウマチ学会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2015-04-23
• [Remarks] 東北大学 血液・免疫病学分野
  • URL: http://www.rh.med.tohoku.ac.jp/index.html