title: Recombinant EPO therapy increases erythrocyte expression of complement regulatory proteins.
abstract: BACKGROUND
  One of the complications of hemodialysis (HD) therapy is anemia caused by erythropoietin (EPO) deficiency. Recombinant EPO (rEPO) has been used routinely as a supplemental treatment. Erythrocyte expression of the complement regulatory proteins decay accelerating factor (DAF) and CD59 restricts complement activation and inhibits hemolysis. We hypothesized that the efficacy of rEPO treatment may be caused in part by the ability of rEPO to increase erythrocyte expression of DAF and CD59.
  
  
  METHODS
  DAF, CD59, and complement receptor 1 (CR1) levels were analyzed for a group of 95 HD patients and compared with those of a control group. To evaluate effects of discontinuation of rEPO therapy, rEPO therapy was stopped for 12 HD patients until hematocrits decreased to less than 25%. DAF and CD59 levels then were reanalyzed.
  
  
  RESULTS
  In the 95 HD patients, three factors correlated significantly: DAF and CD59 (r = 0.642), DAF and CR1 (r = 0.503), and CD59 and CR1 (r = 0.324), whereas no correlations were found in the group of 42 healthy controls. In the experiment in which rEPO therapy was discontinued, 8 of 12 patients reached the defined level of anemia 4 to 7 weeks after rEPO treatment had been withheld. Both DAF and CD59 levels decreased significantly after discontinuation of rEPO therapy (P < 0.01). DAF and CD59 levels increased in all 8 patients after rEPO treatment was reinitiated (P < 0.01), and CR1 levels increased in 5 of 8 patients. Four of 12 patients showed no evidence of anemia after discontinuation of rEPO treatment. In these patients, DAF, CD59, and CR1 levels did not change before or after withholding rEPO therapy.
  
  
  CONCLUSIONS
  One of the mechanisms mediating the efficacy of EPO therapy is increased DAF and CD59 expression.
authors.affiliation: Department of Internal Medicine II, Nihon University School of Medicine, Tokyo, Japan. hori@med.nihon-u.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohi
authors.forename: Mariko
authors.initials: M
authors.lastname: Tamano
authors.forename: Sukemasa
authors.initials: S
authors.lastname: Sudo
authors.forename: Noriko
authors.initials: N
authors.lastname: Okada
mesh_terms: D000740:Anemia / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D018958:CD55 Antigens / Q000096:biosynthesis* / Q000097:blood; D018957:CD59 Antigens / Q000096:biosynthesis* / Q000097:blood; D002908:Chronic Disease; D003176:Complement C3 / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism*; D004921:Erythropoietin / Q000172:deficiency / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D005921:Glomerulonephritis / Q000097:blood; D006801:Humans; D008875:Middle Aged; D011951:Receptors, Complement / Q000097:blood; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000009:adverse effects / Q000379:methods; D051437:Renal Insufficiency / Q000097:blood / Q000628:therapy
chemical_list: D018958:CD55 Antigens; D018957:CD59 Antigens; D003176:Complement C3; D011951:Receptors, Complement; D011994:Recombinant Proteins; D004921:Erythropoietin