NKG2D-mediated immunity in bone marrow failure syndromes

2012 Fiscal Year Final Research Report

• 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
• Keywords: 特発性造血障害 / NKG2D免疫 / PNH

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, Murakami Y, Nagata M, Horikawa K, Nagakura S, Yonemura Y, Murata S, Sonoki T, Kinoshita T, Nakakuma H.
  • Journal Title: 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 Volume: 160.1 Pages: 114-116
  • DOI: 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 Pages: 3866-3868
  • DOI: 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
• [Remarks]
  • URL: http://www.wakayama-med.ac.jp/med/ketunai/index.html