Shichishima Tsutomu, Noji Hideyoshi
First Department of Internal Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima 960-1295, Japan.
Hematology. 2002 Aug;7(4):211-27. doi: 10.1080/1024533021000024094.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder which is manifest by complement-mediated hemolysis, venous thrombosis, and bone marrow failure. Complement-mediated hemolysis in PNH is explained by the deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins, CD55 and CD59 on erythrocyte surfaces. All the PNH patients had phosphatidylinositol glycan-class A (PIG-A) gene abnormalities in various cell types, indicating that PIG-A gene mutations cause the defects in GPI-anchored proteins that are essential for the pathogenesis of PNH. In addition, a PIG-A gene abnormality results in a PNH clone. Bone marrow failure causes cytopenias associated with a proliferative decrease of its hematopoietic stem cells and appears to be related to a pre-leukemic state. Although it is unclear how a PNH clone expands in bone marrow, it is considered that the most important hypothesis implicates negative selection of a PNH clone, but it does not explain the changes in the clinical features at the terminal stage of PNH. Recently, it has been suggested that an immune mechanism, in an HLA-restricted manner, plays an important role in the occurrence or selection of a PNH clone and GPI may be a target for cytotoxic-T lymphocytes. Also, it has been indicated that the Wilms' tumor gene (WT1) product is related to a PNH clone, but the significance of WT1 expression is not clear because of the functional diversity of the gene. To elucidate this problem, it is important to know the pathophysiology of bone marrow failure in detail and how bone marrow failure affects hematopoietic stem cells and immune mechanisms in bone marrow failure syndromes.
阵发性睡眠性血红蛋白尿（PNH）是一种获得性克隆性血液系统疾病，表现为补体介导的溶血、静脉血栓形成和骨髓衰竭。PNH中补体介导的溶血是由于红细胞表面糖基磷脂酰肌醇（GPI）锚定蛋白CD55和CD59的缺乏所致。所有PNH患者在各种细胞类型中均存在磷脂酰肌醇聚糖A类（PIG-A）基因异常，表明PIG-A基因突变导致GPI锚定蛋白缺陷，而这是PNH发病机制所必需的。此外，PIG-A基因异常导致PNH克隆形成。骨髓衰竭导致血细胞减少，与其造血干细胞增殖减少相关，且似乎与白血病前期状态有关。虽然尚不清楚PNH克隆如何在骨髓中扩增，但认为最重要的假说是PNH克隆的阴性选择，但这并不能解释PNH终末期临床特征的变化。最近有人提出，免疫机制以HLA限制的方式在PNH克隆的发生或选择中起重要作用，GPI可能是细胞毒性T淋巴细胞的靶标。此外，有研究表明威尔姆斯瘤基因（WT1）产物与PNH克隆有关，但由于该基因功能的多样性，WT1表达的意义尚不清楚。为阐明这一问题，详细了解骨髓衰竭的病理生理学以及骨髓衰竭如何影响造血干细胞和骨髓衰竭综合征中的免疫机制非常重要。
