Deficiency of the homologous restriction factor in paroxysmal nocturnal hemoglobinuria.
The affected E of two patients with paroxysmal nocturnal hemoglobinuria (PNH) were enriched by lysing the unaffected, normal E with anti-human decay-accelerating factor (DAF) and guinea pig serum. The membranes of the unlysed, DAF-deficient cells (PNH-E) were dissolved and examined by SDS-PAGE and immunoblotting using an antiserum to homologous restriction factor (HRF). Whereas the 65 kD complement regulatory protein was readily detectable in the normal controls, it was completely lacking in both samples of PNH-E membranes. Functional studies likewise indicated the absence of HRF activity from PNH-E. When radiolabeled, isolated HRF protein was offered to PNH-E, it became firmly attached to the cell. Approximately 1,000 molecules of HRF per cell reduced the characteristic susceptibility of these cells to reactive lysis by C5b-9 to nearly normal levels. The results suggest that HRF, which is known to control the action of C8 and C9 on normal human E membranes, is deficient in PNH, as well as acetylcholinesterase and DAF.
D001798:Blood Proteins / Q000172:deficiency* / Q000276:immunology / Q000502:physiology; D018958:CD55 Antigens; D018957:CD59 Antigens; D002352:Carrier Proteins; D002469:Cell Separation; D003169:Complement Inactivator Proteins; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood*; D006461:Hemolysis; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D008565:Membrane Proteins / Q000172:deficiency / Q000276:immunology* / Q000502:physiology
D001798:Blood Proteins; D018958:CD55 Antigens; D018957:CD59 Antigens; D002352:Carrier Proteins; D003169:Complement Inactivator Proteins; D007106:Immune Sera; D008565:Membrane Proteins; C051590:CD59 protein, human