| RRC ID |
1373
|
| 著者 |
Feng X, Chuhjo T, Sugimori C, Kotani T, Lu X, Takami A, Takamatsu H, Yamazaki H, Nakao S.
|
| タイトル |
Diazepam-binding inhibitor-related protein 1: a candidate autoantigen in acquired aplastic anemia patients harboring a minor population of paroxysmal nocturnal hemoglobinuria-type cells.
|
| ジャーナル |
Blood
|
| 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.
|
| 巻・号 |
104(8)
|
| ページ |
2425-31
|
| 公開日 |
2004-10-15
|
| DOI |
10.1182/blood-2004-05-1839
|
| PII |
S0006-4971(20)43304-X
|
| PMID |
15217832
|
| MeSH |
Anemia, Aplastic / blood
Anemia, Aplastic / immunology*
Anemia, Aplastic / metabolism
Anemia, Aplastic / pathology*
Animals
Antibodies / immunology
Autoantigens / blood
Autoantigens / immunology*
Autoantigens / metabolism
Cell Differentiation
Cell Line
DNA, Complementary / genetics
Diazepam Binding Inhibitor / blood
Diazepam Binding Inhibitor / immunology*
Diazepam Binding Inhibitor / metabolism
Enzyme-Linked Immunosorbent Assay
Epitopes / immunology
Gene Expression Regulation
Hemoglobinuria, Paroxysmal / immunology*
Hemoglobinuria, Paroxysmal / metabolism
Hemoglobinuria, Paroxysmal / pathology*
Humans
Mice
Myelodysplastic Syndromes / immunology
Myelodysplastic Syndromes / metabolism
T-Lymphocytes / cytology
T-Lymphocytes / immunology
|
| IF |
17.794
|
| 引用数 |
49
|
|
WOS 分野
|
HEMATOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
K562(RCB0027)
KU812(RCB0495)
U-937 DE-4(RCB0435)
MOLT-4(RCB0206) |
