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- Title
Increased susceptibility to erythrocyte C5b-9 deposition and complement-mediated lysis in chronic renal failure.
- Authors
HIMMELFARB, JONATHAN; MCMONAGLE, ELLEN; HOLBROOK, DIANE; HAKIM, RAYMOND
- Abstract
Increased susceptibility to erythrocyte C5b-9 deposition and complement-mediated lysis in chronic renal failure. Background. Decreased red blood cell survival contributes to the anemia of chronic renal failure patients. Because patients on chronic dialysis therapy are frequently exposed to excessive complement activation, we investigated the susceptibility of this patient population to erythrocyte C5b-9 deposition, complement-mediated lysis, and ghost formation. Methods. We developed a flow cytometric assay using antibodies to both glycophorin and the C5b-9 complex to detect C5b-9 deposition on intact erythrocytes and erythrocyte ghosts. Serum C5b-9 levels and C5b-9 deposition on erythrocyte ghosts were measured by enzyme-linked immunosorbent assay. Results. A significant increase in C5b-9 deposition on intact erythrocytes was demonstrated in patients with advanced chronic renal failure (2.2 ± 0.5%) and in patients on chronic maintenance hemodialysis (2.3 ± 0.4%) compared with normal volunteers (0.9 ± 0.1%, P = 0.005 vs. chronic renal failure, P < 0.001 vs. chronic hemodialysis patients). There was also a significantly higher percentage of C5b-9–positive erythrocyte ghosts in patients with advanced chronic renal failure (20.6 ± 5%) and in chronic hemodialysis patients (15.5 ± 3.1%) compared with normal controls (2.6 ± 0.9%, P ≤ 0.001 vs. advanced chronic renal failure and chronic hemodialysis patients). Treatment of erythrocyte preparations with cobra venom factor, which activates the complement cascade, resulted in dramatic increases in the percentages of C5b-9–positive erythrocyte ghosts in patients with chronic renal failure (49.9 ± 6.9%) and in chronic hemodialysis patients (45.0 ± 4.2%) compared with normal volunteers (22.3 ± 2.7%, P < 0.001 vs. chronic renal failure and chronic hemodialysis patients). Erythrocyte membrane expression of the complement regulatory proteins CD59 and CD55 did...
- Subjects
CHRONIC kidney failure; ERYTHROCYTES; PATIENTS
- Publication
Kidney International, 1999, Vol 55, Issue 2, p659
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.1999.00277.x