title: Diazepam-binding inhibitor-related protein 1: a candidate autoantigen in acquired aplastic anemia patients harboring a minor population of paroxysmal nocturnal hemoglobinuria-type cells.
abstract: 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.
authors.affiliation: Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Xingmin
authors.initials: X
authors.lastname: Feng
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Chuhjo
authors.forename: Chiharu
authors.initials: C
authors.lastname: Sugimori
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kotani
authors.forename: Xuzhang
authors.initials: X
authors.lastname: Lu
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Takami
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamatsu
authors.forename: Hirohito
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
mesh_terms: D000741:Anemia, Aplastic / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001324:Autoantigens / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D026261:Diazepam Binding Inhibitor / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005786:Gene Expression Regulation; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D000906:Antibodies; D001324:Autoantigens; D018076:DNA, Complementary; D026261:Diazepam Binding Inhibitor; D000939:Epitopes