Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Blood. 2014 Oct 30;124(18):2804-11. doi: 10.1182/blood-2014-02-522128. Epub 2014 Sep 18.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare bone marrow failure disorder that manifests with hemolytic anemia, thrombosis, and peripheral blood cytopenias. The absence of two glycosylphosphatidylinositol (GPI)-anchored proteins, CD55 and CD59, leads to uncontrolled complement activation that accounts for hemolysis and other PNH manifestations. GPI anchor protein deficiency is almost always due to somatic mutations in phosphatidylinositol glycan class A (PIGA), a gene involved in the first step of GPI anchor biosynthesis; however, alternative mutations that cause PNH have recently been discovered. In addition, hypomorphic germ-line PIGA mutations that do not cause PNH have been shown to be responsible for a condition known as multiple congenital anomalies-hypotonia-seizures syndrome 2. Eculizumab, a first-in-class monoclonal antibody that inhibits terminal complement, is the treatment of choice for patients with severe manifestations of PNH. Bone marrow transplantation remains the only cure for PNH but should be reserved for patients with suboptimal response to eculizumab.
阵发性睡眠性血红蛋白尿症（PNH）是一种罕见的骨髓衰竭性疾病，表现为溶血性贫血、血栓形成和外周血细胞减少症。两种糖基磷脂酰肌醇（GPI）锚定蛋白 CD55 和 CD59 的缺失导致不受控制的补体激活，这解释了溶血和其他 PNH 表现。GPI 锚蛋白缺陷几乎总是由于参与 GPI 锚生物合成第一步的磷脂酰肌醇聚糖类 A（PIGA）基因的体细胞突变引起的；然而，最近发现了导致 PNH 的其他突变。此外，不会导致 PNH 的低功能生殖系 PIGA 突变已被证明是一种称为多种先天异常-张力减退-癫痫综合征 2 的疾病的原因。依库珠单抗是一种首创的单克隆抗体，可抑制末端补体，是治疗 PNH 严重表现的首选药物。骨髓移植仍然是 PNH 的唯一治愈方法，但应保留给对依库珠单抗反应不佳的患者。
