Erythrocyte membrane protein deficiencies in paroxysmal nocturnal hemoglobinuria.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder characterized by intermittent hemolytic anemia. Membrane abnormalities of blood cells from patients with PNH are the reason for the unusual sensitivity to lysis by autologous plasma complement. A patient with typical clinical disease consistent with PNH is described together with a few strategies and pitfalls for treatment. Commonly used in vitro assays are discussed that document the complement-mediated lysis of aberrant PNH erythrocytes. Membrane-associated proteins that are abnormal in PNH cells, the characteristics of these proteins, and their mechanism(s) of action are described; these include the decay accelerating factor that inhibits the C3/C5 convertases of both complement pathways on cell surfaces, the C8 binding protein that modulates a step in terminal complement lysis, and other proteins that regulate complement-mediated lysis at early or late steps of the complement cascade.
Schultz
D R
DR
Department of Medicine, University of Miami School of Medicine, Florida 33101.
D000328:Adult; D001798:Blood Proteins / Q000172:deficiency* / Q000276:immunology / Q000502:physiology; D018958:CD55 Antigens; D018957:CD59 Antigens; D002352:Carrier Proteins / Q000276:immunology / Q000502:physiology*; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D003169:Complement Inactivator Proteins / Q000172:deficiency* / Q000276:immunology / Q000502:physiology; D004910:Erythrocyte Membrane / Q000737:chemistry*; D005260:Female; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency* / Q000276:immunology / Q000502:physiology; D011951:Receptors, Complement / Q000172:deficiency* / Q000276:immunology / Q000502:physiology; D017463:Receptors, Complement 3b
D001798:Blood Proteins; D018958:CD55 Antigens; D018957:CD59 Antigens; D002352:Carrier Proteins; D003176:Complement C3; D003181:Complement C4; D003169:Complement Inactivator Proteins; D008565:Membrane Proteins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; C051590:CD59 protein, human