Diazepam-binding inhibitor-related protein 1: a candidate autoantigen in acquired aplastic anemia patients harboring a minor population of paroxysmal nocturnal hemoglobinuria-type cells.
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.
Feng
Xingmin
X
Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
Chuhjo
Tatsuya
T
Sugimori
Chiharu
C
Kotani
Takeharu
T
Lu
Xuzhang
X
Takami
Akiyoshi
A
Takamatsu
Hiroyuki
H
Yamazaki
Hirohito
H
Nakao
Shinji
S
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
D000906:Antibodies; D001324:Autoantigens; D018076:DNA, Complementary; D026261:Diazepam Binding Inhibitor; D000939:Epitopes