补体系统（缺陷）与疾病

Paroxymal nocturnal hemoglobinuria, or PNH, which manifests as increased fragility of erythrocytes, leading to chronic hemolytic anemia, pancytopenia (loss of blood cells of all types) and venous thrombosis (formation of blood clots). The name PNH derives from the presence of hemoglobin in the urine, most commonly observed in the first urine passed after a night’s sleep. The cause of PNH is a general defect in synthesis of cell-surface proteins, which affects the expression of two regulators of complement, DAF (decay accelerating factor or CD55) and MIRL (membrane inhibitor of reactive lysis or CD59).

DAF and MIRL are cell-surface proteins that function as inhibitors of complement-mediated cell lysis, but act at different stages of the process. DAF inhibits cell lysis by causing dissociation and inactivation of the C3 convertases of the classical, lectin, and alternative pathways. MIRL acts later in the pathway by binding to the C5b678 complex, which inhibits C9 binding and prevents formation of the pores that destroy the cell under attack. Both proteins are expressed on erythrocytes as well as a number of other hematopoetic cell types. Deficiency in these proteins leads to highly increased sensitivity of host cells to the lytic effects of the host’s complement activity. PNH, the clinical consequence of deficiency in DAF and MIRL, is a chronic disease with a mean survival time between 10 and 15 years. The most common causes of mortality in PNH are venous thrombosis affecting hepatic veins and progressive bone marrow failure.