阵发性睡眠性血红蛋白尿症发病机制、诊断及治疗进展

Advances in pathogenesis, diagnosis and treatment of paroxysmal nocturnal hemoglobinuria

阵发性睡眠性血红蛋白尿症（PNH）是一种罕见的获得性造血干细胞基因突变引起的疾病。已明确磷脂酰肌醇聚糖A（PIGA）基因突变是PNH患者血管内溶血的分子病因，但克隆性增殖的机制仍有待揭示。PNH与再生障碍性贫血、骨髓增生异常综合征关系密切。流式细胞术检测锚连蛋白缺陷是诊断PNH的金标准，但基于细胞表型诊断的PNH在病因上仍是一组异质性疾病。依库珠单抗可有效减少PNH血管内溶血，显著改善患者的生命质量，但仍属对症治疗。对PNH发病机制的进一步研究有助于正确认识患者的内在病因、提高鉴别诊断能力和改善治疗。文章对结合近年来的研究进展进行综述。

Paroxysmal nocturnal hemoglobinuria （PNH） is a rare disorder of hematopoietic stem cells due to acquisition of somatic mutations. Somatic mutations in phosphatidylinositol glycan class A （PIGA） account for intravascular hemolysis and other PNH manifestations, but the pathophysiology of clonal expansion of PNH cells cannot be elucidated clearly. PNH is closely related to aplastic anemia and myelodysplastie syndromes. Today, the gold standard for PNH is flow cytometry to detect the absence or severe deficiency of glycosylphosphatidylinositol （GPI）-anchored proteins on white and red blood cells. However, PNH diagnosed by phenotype is a group of heterogeneous disease in pathogenesis. Eculizumab, a first-in-class monoclonal antibody that inhibits terminal complement, is highly effective in stopping intravascular hemolysis and improving quality of life. Further research on the pathogenesis of PNH would be helpful to understand the underlying reasons for PNH phenotype ceils in different patients, improve differential diagnosis and more targeted and specific therapy. Research progress in recent years will be reviewed in this article.