Establishment of a diagnostics of autoimmune bone marrow failure by means of examination of antibody to hematopoietic stem Cells
| Project/Area Number |
14570969
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Kanazawa University |
|---|
Principal Investigator |
CHUHJO Tatsuya Kanazawa University, University hospital, Assistant, 医学部附属病院, 助手 (00303298)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NAKAO Shinji Kanazawa University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (70217660)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
|---|
| Keywords | autoantibody / aplastic anemia / PNH / DR15 / DRS-1 / helper T-cell / SEREX / MDS / DR 15 / Clonality / SEREX / 骨髄異形成症候群 / 発作性夜間血色素尿症 / 自己免疫疾患 / 造血幹細胞 |
|---|
| Research 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 I (DRS-1). Enzyme-linked immunosorbent assay (ELISA) revealed high titers of antiミ 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ミ 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-DRI5, 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 DRB 1^*1501 and DRS-1. Enzyme-linked immunospot assay demonstrated increased frequency of T-cell precursors specific to the DRS-1 peptide in other HLA-DRl5+ 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.
|
Report
(3 results)
Research Products
(10 results)
