Increased sensitivity to complement of erythroid and myeloid progenitors in paroxysmal nocturnal hemoglobinuria.
Paroxysmal nocturnal hemoglobinuria is an acquired hemolytic anemia characterized by a membrane defect leading to increased sensitivity of erythrocytes, granulocytes, platelets, and bone-marrow erythroid and myeloid cells to complement-mediated lysis. To determine whether the phenotype of paroxysmal nocturnal hemoglobinuria is also expressed on erythroid and myeloid progenitors, marrow cells from five patients with the disease were exposed to a sucrose hemolytic system and then assayed for colony-forming units-erythroid (CFU-E), burst-forming units-erythroid (BFU-E), and colony-forming units-granulocyte/macrophage (CFU-GM). A 50 percent or greater decrease in the numbers of erythroid and myeloid colonies was noted when marrow cells from the patients with paroxysmal nocturnal hemoglobinuria were exposed to a sucrose solution of low ionic strength in the presence of complement but not in its absence. Such a decrease was not noted in similarly treated normal marrow cells or in marrow cells from a patient with the disease in remission. These results suggest that in paroxysmal nocturnal hemoglobinuria, CFU-E, BFU-E, and CFU-GM express a membrane abnormality similar to that on erythrocytes, and that the disease is the result of a change occurring at the level of the pluripotent hematopoietic stem cell.
D000328:Adult; D003114:Colony-Forming Units Assay; D003165:Complement System Proteins / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000276:immunology*
D003165:Complement System Proteins