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抗造血幹細胞抗体の検出による自己免疫性骨髄不全の診断法の確立
https://doi.org/10.24517/00063695
https://doi.org/10.24517/00063695b9f6a0a0-07ee-4aa2-a394-2556e845b230
名前 / ファイル | ライセンス | アクション |
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HO-PR-CHUHJYO-T-kaken 2006-2p.pdf (92.3 kB)
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Item type | 報告書 / Research Paper(1) | |||||
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公開日 | 2021-10-22 | |||||
タイトル | ||||||
タイトル | 抗造血幹細胞抗体の検出による自己免疫性骨髄不全の診断法の確立 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Establishment of a diagnostics of autoimmune bone marrow failure by means of examination of antibody to hematopoietic stem Cells | |||||
言語 | ||||||
言語 | jpn | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_18ws | |||||
資源タイプ | research report | |||||
ID登録 | ||||||
ID登録 | 10.24517/00063695 | |||||
ID登録タイプ | JaLC | |||||
著者 |
中条, 達也
× 中条, 達也 |
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著者別表示 |
Chuhjo, Tatsuya
× Chuhjo, Tatsuya |
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提供者所属 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 金沢大学医学部附属病院 | |||||
書誌情報 |
平成15(2003)年度 科学研究費補助金 基盤研究(C) 研究成果報告書概要 en : 2003 Fiscal Year Final Research Report Summary 巻 2002 – 2003, p. 2p., 発行日 2006-07-10 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 1.再生不良性貧血(再不貧)のうち、HLA-DR15を保有し末梢血中に微小なPNH形質の血球を有する例において、免疫抑制療法に対する反応性がみられた。再不貧患者の末梢血顆粒球のclonalityを検討したところ、主としてPNH血球陰性例にclonalityが確認された。 2.PNH血球陽性の再不貧患者の血清中には、巨核芽球性白血病細胞株UT7の細胞質内蛋白に対する抗体が、間接蛍光抗体法とWestern blot法にて確認された。 3.UT7に対する抗体陽性例の血清にてcDNAライブラリーをスクリーニングして、抗原遺伝子Diazepam binding inhibitors(DBI)-related sequence-1(DRS-1)を同定した。 4.レコンビナントDRS-1蛋白を用いてELISAを行ったところ、PNH血球陽性の再不貧71例中27例(38.5%)に抗DRS-1抗体がみられたが、PNH血球陰性再不貧32例中では2例のみ(6.3%)にしか抗体がみられなかった。 5.定量PCRを用いてDRS-1のmRNAの発現を検討したところ、成熟白血球では発現レベルが低かったが、UT-7やCD34陽性の骨髄造血細胞ではレベルが高かった。 6.DR15上にDRS-1のアミノ酸配列上のCD4 epitope(同配列は、抗体の認識するhot spot 191-204と重なっていた)のペプチドを付加して、抗DRS-1抗体を持つ再不貧患者末梢血T細胞を刺激して得られた細胞障害性T細胞は、DRB1*1501を遺伝子導入されDRS-1を高発現しているL cell(マウス線維芽細胞)のみを選択的に障害した。 7.Enzyme-linked immunospot assayにより、HLA-DR15を保有し抗DRS-1抗体を持つ再不貧患者末梢血中において、このCD4 epitopeに特異的なT細胞が高頻度に見いだされた。 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 研究課題/領域番号:14570969, 研究期間(年度):2002 – 2003 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 出典:「抗造血幹細胞抗体の検出による自己免疫性骨髄不全の診断法の確立」研究成果報告書 課題番号14570969 (KAKEN:科学研究費助成事業データベース(国立情報学研究所)) (https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-14570969/145709692003kenkyu_seika_hokoku_gaiyo/)を加工して作成 |
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著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/ja/search/?kw=00303298 | |||||
関連名称 | https://kaken.nii.ac.jp/ja/search/?kw=00303298 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-14570969/ | |||||
関連名称 | https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-14570969/ | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-14570969/145709692003kenkyu_seika_hokoku_gaiyo/ | |||||
関連名称 | https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-14570969/145709692003kenkyu_seika_hokoku_gaiyo/ |