Paroxysmal nocturnal hemoglobinuria from bench to bedside.
Paroxysmal nocturnal hemoglobinuria from bench to bedside.
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DOI：
10.1111/j.1752-8062.2011.00262.x
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Brodsky RA
中科院分区：
文献类型：
--
作者：
Pu JJ;Brodsky RA
阵发性夜间血红蛋白尿（PNH）是一种罕见的血液病，表现为变异性。在过去的25年里，临床和实验室研究已经揭示了PNH的大部分基础科学基础，并导致了一种高效靶向治疗的发展。PNH起源于一种多能造血干细胞（HSC），该干细胞在一种称为磷脂酰肌醇聚糖锚定生物合成（a类猪- a）的基因中获得体细胞突变。猪- a基因是糖基磷脂酰肌醇（GPI）锚定生物合成的第一步所必需的。GPI锚点合成失败导致所有利用GPI附着在质膜上的蛋白质缺失。两个gpi锚定蛋白CD55和CD59是补体调节蛋白；它们在PNH细胞表面的缺失导致补体介导的溶血。游离血红蛋白的释放导致一氧化氮的清除，并导致许多临床表现，包括食管痉挛、疲劳和可能的血栓形成。气溶素是一种形成孔的毒素，它与GPI锚定蛋白结合，杀死正常细胞，但不杀死PNH细胞。荧光化气溶素变体（fler）结合gpi锚定蛋白，可作为诊断PNH的新试剂。Eculizumab是一种针对C5的人源化单克隆抗体，是首个有效治疗PNH的药物。
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease that presents with protean manifestations. Clinical and laboratory investigation over the past 25 years have uncovered most of the basic science underpinnings of PNH and have led to the development of a highly effective targeted therapy. PNH originates from a multipotent hematopoietic stem cell (HSC) that acquires a somatic mutation in a gene called phosphatidylinositol glycan anchor biosynthesis, class A (PIG-A). The PIG-A gene is required for the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Failure to synthesize GPI anchors leads to an absence of all proteins that utilize GPI to attach to the plasma membrane. Two GPI-anchor proteins, CD55 and CD59, are complement regulatory proteins; their absence on the surface of PNH cells leads to complement-mediated hemolysis. The release of free hemoglobin leads to scavenging of nitric oxide and contributes to many clinical manifestations, including esophageal spasm, fatigue, and possibly thrombosis. Aerolysin, a pore-forming toxin, binds GPI anchored proteins and kills normal cells, but not PNH cells. A fluorescinated aerolysin variant (FLAER) binds GPI-anchor and serves as a novel reagent diagnosing PNH. Eculizumab, a humanized monoclonal antibody against C5, is the first effective drug therapy for PNH.
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DOI：
10.4049/jimmunol.181.11.8068
发表时间：
2008-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Huang Y;Qiao F;Atkinson C;Holers VM;Tomlinson S
通讯作者：
Tomlinson S
DOI：
10.1073/pnas.0802749105
发表时间：
2008-11-25
影响因子：
11.1
作者：
Dingli, David;Luzzatto, Lucio;Pacheco, Jorge M.
通讯作者：
Pacheco, Jorge M.
影响因子：
158.5
作者：
Ham, TH
通讯作者：
Ham, TH
影响因子：
30.8
作者：
Krawitz, Peter M.;Schweiger, Michal R.;Robinson, Peter N.
通讯作者：
Robinson, Peter N.
影响因子：
158.5
作者：
Almeida, Antonio M.;Murakami, Yoshiko;Karadimitris, Anastasios
通讯作者：
Karadimitris, Anastasios