NDT Advance Access originally published online on April 6, 2004
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Nephrol Dial Transplant (2004) 19: 1467-1473
Nephrol Dial Transplant Vol. 19 No. 6 © ERA-EDTA 2004; all rights reserved
Original Article
Quantitative polymorphism of complement receptor type 1 (CR1) in patients undergoing haemodialysis
1Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo and 2Kasukabe-Kisen Hospital, Saitama, Japan
Correspondence and offprint requests to: Mariko Tamano, PhD, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Email: mtamano{at}med.juntendo.ac.jp
Background. The level of complement receptor type 1 (CR1) on erythrocytes (E-CR1) is determined by the presence of high (H) or low (L) expression alleles. We investigated whether acquired loss of E-CR1 occurs in haemodialysis patients and, if so, which factors may contribute to acquired loss of E-CR1 in these patients.
Methods. The E-CR1 level was determined in 195 Japanese haemodialysis patients, and we selected patients with a high or low E-CR1 level. In patients with low E-CR1 expression, sequence analysis of polymorphic sites (A3650G and C5507G) in the CR1 gene was performed. To assess the effect of the type of dialysis membrane used in the patients with low E-CR1 expression, the dialysis membrane was changed from a cellulose membrane to a biocompatible membrane (to a polyacrylonitrile membrane and then to a polysulfone membrane). To evaluate the susceptibility of E-CR1 to proteolysis, erythrocytes were incubated with various concentrations of trypsin, and the level of remaining CR1 on the erythrocytes was determined.
Results. Among patients with high E-CR1 expression (n = 30), 87% had HH alleles and 13% had HL alleles. Among patients with low E-CR1 expression (n = 29), 24% had LL alleles, 45% had HL alleles and 31% had HH alleles. Nucleotides 3650G and 5507G in the CR1 gene were associated with the L allele. Nucleotides 3650A and 5507C were associated with the H allele. Only one patient with HH alleles had nucleotides 3650G and 5507C. Three months after changing the haemodialysis membrane, the E-CR1 level significantly increased (P<0.02). The proteolysis curves of E-CR1 of patients with low or high E-CR1 expression and normal controls were similar.
Conclusion. Use of a non-biocompatible dialysis membrane may contribute to acquired loss of E-CR1 in haemodialysis patients.
Keywords: complement receptor type 1; CR1; dialysis membrane; haemodialysis; polymorphism