title: NKG2D-mediated immunity underlying paroxysmal nocturnal haemoglobinuria and related bone marrow failure syndromes.
abstract: It is considered that a similar immune mechanism acts in the pathogenesis of bone marrow (BM) failure in paroxysmal nocturnal haemoglobinuria (PNH) and its related disorders, such as aplastic anaemia (AA) and myelodysplastic syndromes (MDS). However, the molecular events in immune-mediated marrow injury have not been elucidated. We recently reported an abnormal expression of stress-inducible NKG2D (natural-killer group 2, member D) ligands, such as ULBP (UL16-binding protein) and MICA/B (major histocompatibility complex class I chain-related molecules A/B), on granulocytes in some PNH patients and the granulocyte killing by autologous lymphocytes in vitro. The present study found that the expression of NKG2D ligands was common to both granulocytes and BM cells of patients with PNH, AA, and MDS, indicating their exposure to some incitement to induce the ligands. The haematopoietic colony formation in vitro by the patients' marrow cells significantly improved when their BM cells were pretreated with antibodies against NKG2D receptor, suggesting that the antibodies rescued haematopoietic cells expressing NKG2D ligands from damage by autologous lymphocytes with NKG2D. Clinical courses of patients with PNH and AA showed a close association of the expression of NKG2D ligands with BM failure and a favourable response to immunosuppressive therapy. We therefore propose that NKG2D-mediated immunity may underlie the BM failure in PNH and its-related marrow diseases.
authors: Department of Haematology/Oncology, Wakayama Medical University, Wakayama, Japan.
authors: Nobuyoshi
authors: N
authors: Hanaoka
authors: Hideki
authors: H
authors: Nakakuma
authors: Kentaro
authors: K
authors: Horikawa
authors: Shoichi
authors: S
authors: Nagakura
authors: Yasuchika
authors: Y
authors: Tsuzuki
authors: Masaya
authors: M
authors: Shimanuki
authors: Kensuke
authors: K
authors: Kojima
authors: Yuji
authors: Y
authors: Yonemura
authors: Tatsuya
authors: T
authors: Kawaguchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D006098:Granulocytes / Q000276:immunology; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D008024:Ligands; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D009190:Myelodysplastic Syndromes / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; C094840:MR1 protein, human; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012333:RNA, Messenger; C423231:ULBP1 protein, human