Relationship between decay accelerating factor deficiency, diminished acetylcholinesterase activity, and defective terminal complement pathway restriction in paroxysmal nocturnal hemoglobinuria erythrocytes.
Paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes exhibit abnormalities in decay accelerating factor (DAF), acetylcholinesterase, and resistance to autologous C5b-9 attack. To investigate the nature of the lesion underlying PNH cells, we examined the relationship of these abnormalities to one another. Analyses of DAF in acetylcholinesterase-negative erythrocytes revealed that these two abnormalities involve functionally independent molecules, coincide precisely in the same cell populations, and are similarly expressed in PNH II and more complement-sensitive PNH III erythrocytes. The DAF and acetylcholinesterase deficiencies contrast with the C3b/C4b receptor (CR1) deficit, which is less profound and similarly distributed in complement-insensitive cell populations. Hemolytic studies showed that defective resistance to autologous C5b-9 attack is mediated by another mechanism. Whereas reconstitution of PNH II erythrocytes with DAF completely corrected their complement sensitivity, DAF reconstitution of PNH III erythrocytes restored their ability to circumvent C3b uptake but had no effect on their heightened susceptibility to reactive lysis. Assays of complement-insensitive (PNH I) erythrocytes surviving after reactive lysis disclosed partial DAF and acetylcholinesterase deficits. These findings indicate that the PNH lesion involves multiple membrane components and that PNH I erythrocytes are also abnormal.
D000110:Acetylcholinesterase / Q000172:deficiency*; D018958:CD55 Antigens; D003179:Complement C3b / Q000276:immunology; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism*; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000276:immunology; D006461:Hemolysis; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency*
D018958:CD55 Antigens; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D008565:Membrane Proteins; D003179:Complement C3b; D003165:Complement System Proteins; D000110:Acetylcholinesterase