NKG2D-mediated immunity in bone marrow failure syndromes

• Project/Area Number: 23791087
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Wakayama Medical University
• Principal Investigator: HANAOKA Nobuyoshi 和歌山県立医科大学, 医学部, 講師 (40433370)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 特発性造血障害 / NKG2D免疫 / PNH / 内科 / 免疫学 / NKG2D / 造血障害

Research Abstract

Acquired idiopathic bone marrow failure responds to immunosuppressive therapy (IST), indicating that marrow failure is immune-mediated. However, molecular pathogenesis of the immune, including on hematopoietic progenitor cells,is unknown. In the present study, we show that NKG2D-mediated immunity closely links with marrow injury in a patient with paroxysmal nocturnal hemoglobinuria. We found both that NKG2D ligands including ULBP and MICA/B were pathologically expressed on granulocytes, whereas NKG2D receptor on lymphocytes of the patient, and that IST was effective for the marrow failure. We then propose that NKG2D-mediated immunity could directly visualizeimmune condition of the marrow failure. Currently, we are confirming the NKG2D-associated immunity decides the timing of discontinuation of IST in the patient.ient.

Research Products

• [Journal Article] Occupancy of whole blood cells by a single PIGA-mutant clone with HMGA2 amplification in a paroxysmal nocturnal haemoglobinuria patient having blood cells with NKG2D ligands (2013)
  • Author(s): Hanaoka, N., Y. Murakami, M. Nagata, K. Horikawa, S. Nagakura, Y. Yonemura, S. Murata, T. Sonoki, T. Kinoshita, H. Nakakuma
  • Journal Title: Br. J. Haematol. Volume: 160 Issue: 1 Pages: 114-116
  • DOI: 10.1111/bjh.12093
  • Peer Reviewed
• [Journal Article] Persistently high quality of life conferred by coexisting congenital deficiency of terminal complement C9 in a paroxysmal nocturnal hemoglobinuria patient. (2012)
  • Author(s): Hanaoka N, Murakami Y, Nagata M, Nagakura S, Yonemura Y, Sonoki T, Kinoshita T, Nakakuma H.
  • Journal Title: Blood Volume: 119(16) Issue: 16 Pages: 3866-3868
  • DOI: 10.1182/blood-2012-02-408161
  • Peer Reviewed
• [Presentation] Pathophysiology of extravascular hemolysis in paroxysmal nocturnal hemoglobinuria (2012)
  • Author(s): Hanaoka N, Murakami Y, Nagata M, Nagakura S, Yonemura Y, Sonoki T, Kinoshita T, Nakakuma H.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-19
• [Presentation] Pathophysiology of extravascular hemolysis in paroxysmal nocturnal hemoglobinuria. (2012)
  • Author(s): Nobuyoshi Hanaoka
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
• [Remarks]
  • URL: http://www.wakayama-med.ac.jp/med/ketunai/index.html