Diazepam-binding inhibitor-related protein 1: a candidate autoantigen in acquired aplastic anemia patients harboring a minor population of paroxysmal nocturnal hemoglobinuria–type cells

DOI PDF 被引用文献20件
  • Xingmin Feng
    From the Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; and the Protected Environmental Unit, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
  • Tatsuya Chuhjo
    From the Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; and the Protected Environmental Unit, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
  • Chiharu Sugimori
    From the Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; and the Protected Environmental Unit, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
  • Takeharu Kotani
    From the Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; and the Protected Environmental Unit, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
  • Xuzhang Lu
    From the Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; and the Protected Environmental Unit, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
  • Akiyoshi Takami
    From the Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; and the Protected Environmental Unit, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
  • Hiroyuki Takamatsu
    From the Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; and the Protected Environmental Unit, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
  • Hirohito Yamazaki
    From the Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; and the Protected Environmental Unit, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
  • Shinji Nakao
    From the Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; and the Protected Environmental Unit, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.

抄録

<jats:title>Abstract</jats:title><jats:p>To identify candidate antigens in aplastic anemia (AA), we screened proteins derived from a leukemia cell line with serum of an AA patient and identified diazepam-binding inhibitor-related protein 1 (DRS-1). Enzyme-linked immunosorbent assay (ELISA) revealed high titers of anti–DRS-1 antibodies (DRS-1 Abs) in 27 (38.0%) of 71 AA patients displaying increased paroxysmal nocturnal hemoglobinuria (PNH)–type cells (PNH+), 2 (6.3%) of 32 PNH– AA patients, 5 (38.5%) of 13 PNH+ myelodysplastic syndrome (MDS) patients, and none of 42 PNH– MDS patients. DRS-1 gene was abundantly expressed in myeloid leukemia cell lines and in CD34+ cells derived from healthy individuals. Stimulation of T cells from an AA patient displaying high DRS-1 Abs with a putative CD4+ T-cell epitope (amino acid residues [aa's] 191-204) presented by HLA-DR15, which overlapped with a hot spot (aa's 173-198) of DRS-1 Ab epitopes, gave rise to T cells cytotoxic for L cells (murine fibroblasts) that were transfected with DRB1*1501 and DRS-1. Enzyme-linked immunospot assay demonstrated increased frequency of T-cell precursors specific to the DRS-1 peptide in other HLA-DR15+ AA patients displaying high DRS-1 Ab titers. These findings indicate that DRS-1 may serve as an autoantigen eliciting immune attack against hematopoietic stem cells in a subset of AA patients characterized by increased PNH-type cells.</jats:p>

収録刊行物

  • Blood

    Blood 104 (8), 2425-2431, 2004-10-15

    American Society of Hematology

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