WEKO3
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骨髄不全における自己抗原特異的T細胞を介したPNHクローン増幅メカニズムの解明
https://doi.org/10.24517/00051107
https://doi.org/10.24517/000511079124400b-b1a7-49ff-b36c-60564c6a9dc2
名前 / ファイル | ライセンス | アクション |
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ME-PR-NAKAO-S-kaken 2007-9p.pdf (578.9 kB)
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Item type | 報告書 / Research Paper(1) | |||||
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公開日 | 2018-06-18 | |||||
タイトル | ||||||
タイトル | 骨髄不全における自己抗原特異的T細胞を介したPNHクローン増幅メカニズムの解明 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Analysis of mechanisms responsible for clonal expansion of PNH-type hematopoietic stem cells mediated by autoreactive T cells in patients with bone marrow failure | |||||
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 | 10.24517/00051107 | |||||
ID登録タイプ | JaLC | |||||
著者別表示 |
Nakao, Shinji
× Nakao, Shinji |
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書誌情報 |
平成18(2006)年度 科学研究費補助金 基盤研究(B) 研究成果報告書 en : 2006 Fiscal Year Final Research Report 巻 2005-2006, p. 9p., 発行日 2007-05 |
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出版者 | ||||||
出版者 | 金沢大学医薬保健研究域医学系 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Diazepam binding inhibitor-related protein-1(DRS-1)に対する特異的なT細胞が、骨髄不全患者における発作性夜間ヘモグロビン尿症(PNH)形質血球の出現に関与しているか否かを明らかにするため、抗DRS-1抗体を持つPNH型血球陽性の再生不良性貧血(再不貧)患者から、PIG-A遺伝子に異常を持つPNH型lymphoblastoid cell line(LCL)を樹立した。このPNH型LCLにレトロウイルスベクターや電気穿孔法を用いてDRS-1 cDNAの導入を試みたが、インヒビターが存在しているためか、恒常的にDRS-1を発現させることはできなかった。一方、組換えモエシンを用いたELISAを作製し67人の再不貧患者血清を調べたところ、25人(37%)において高力価の抗モエシン抗体が検出された。PNH型血球陽性再不貧患者43人とPNH型血球陰性再不貧患者24人のそれぞれの抗体保有率は47%、21%であり、PNH型血球陽性患者で有意に高頻度に抗モエシン抗体が検出された。モエシンはUT-7、K562などの骨髄系白血病細胞株と健常者由来CD34+細胞からエクソゾームとして細胞外に分泌されていた。これまでに我々が同定した抗DRS-1抗体、PNH型血球と、今回同定したが抗モエシン抗体の少なくとも一つを認めた再不貧患者では26例中22例(85%)が免疫抑制療法に反応して改善したのに対し、いずれも認めない再不貧患者2例では免疫抑制療法が無効であった。これらの所見から、再不貧患者では造血細胞由来のモエシンに対するB細胞の反応が高頻度に起こっており、抗モエシン抗体、抗DRS-1抗体、PNH型血球の検出を組み合わせることによって、免疫病態が関与する再不貧を診断できる可能性が示唆された。抗モエシン抗体を検出するための酵素免疫抗体法を開発し、特許(再生不良性貧血患者血清に存在する自己抗体の検出方法、特願2004-333725)を取得した。 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | In an attempt to determine whether CD4^+ T cells specific to diazepam-binding inhibitor protein-1 (DRS-1) contribute to the survival advantage of paroxysmal nocturnal hemoglobinuria (PNH)-type stem cells, we established a lymphobastoid cell line with PIG-A mutation from an aplastic anemia (AA) patients showing a high titer antibodies speicific to DRS-1. We tried to transfect the PNH-type LCL cells with DRS-1 cDNA using various methods such as retroviral vectors and electroporation to use them as a target of DRS-1 specific CD4^+ T cells. However, all the methods failed to induce expression of DRS-1 gene in LCL cells, probably due to inhibitory mechanisms for the DRS-1 expression inherent to B lymphocytes. Thus, we suspended this experiments and focused on another candidate autoantigen, moesin. We screened the sera of AA patients possessing small populations of PNH-type cells for the presence of antibodies (Abs) which recognize proteins derived from a leukemia cell line, UT-7. Immunoblott ing using proteins derived from lysates or culture supernatants of UT-7 cells revealed the presence of IgG Abs specific to an 80 kD protein. Peptide mass fingerprinting identified this 80 kD protein as moesin. Enzyme-linked immunosorbent assay (ELISA) using recombinant moesin showed high titers of anti-moesin Abs in 25 (37%) of 67 AA patients. Moesin was secreted from several myeloid leukemia cell lines other than UT-7, such as OUN-1 and K562, as an exosomal protein. The presence of anti-moesin Abs was significantly correlated with the presence of PNH-type cells and anti-diazepam-binding inhibitor-related protein-1 (DRS-1) Abs. AA patients that did not show any of these three markers tended to respond poorly to immunosuppressive therapy. These findings suggest that a B-cell response to moesin, possibly derived from hematopoietic cells, frequently occurs in patients with AA and that detection of anti-moesin Abs in combination with other markers may be useful in diagnosing immune pathophysiology in AA patients. |
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内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 研究課題/領域番号:17390275, 研究期間(年度):2005-2006 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 出典:「骨髄不全における自己抗原特異的T細胞を介したPNHクローン増幅メカニズムの解明」研究成果報告書 課題番号17390275 (KAKEN:科学研究費助成事業データベース(国立情報学研究所)) 本文データは著者版報告書より作成 |
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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/search/?qm=70217660 | |||||
関連名称 | https://kaken.nii.ac.jp/search/?qm=70217660 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390275/ | |||||
関連名称 | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390275/ | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17390275/173902752006kenkyu_seika_hokoku_gaiyo/ | |||||
関連名称 | https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17390275/173902752006kenkyu_seika_hokoku_gaiyo/ |