Acquired Loss of Erythrocyte Complement Receptor Type 1 in Patients with Diabetic Nephropathy Undergoing Hemodialysis

Abstract

Background: Complement receptor type 1 on erythrocytes (E-CR1) plays important roles not only in the regulation of complement activation, but also the clearance of immune complexes. Reduced E-CR1 was previously found in patients undergoing hemodialysis (HD). We investigated whether the E-CR1level in HD patients with diabetic nephropathy (DMN) is decreased. The levels of decay accelerating factor (DAF) and CD59 on erythrocytes (E) were also determined to ascertain whether the loss of CR1 is a specific phenomenon or other complement regulatory proteins are also affected. Methods: The levels of CR1, DAF, and CD59 on E were analyzed in 176 HD patients with DMN, 101 HD patients with non-diabetes mellitus renal diseases (non-DMN), and 108 healthy individuals. Hind III restriction fragment length polymorphism of intron 27 of the CR1 gene was analyzed. The serum-soluble CR1 levelwas measured by ELISA. Results: The E-CR1 level was significantly lower in the DMN group than the non-DMN group (p < 0.0001) and healthy individuals (p < 0.05). The E-CR1 level was significantly higher in the non-DMN group than in healthy individuals (p < 0.01). The levels of E-DAF and E-CD59 were significantly lower in the DMN group than non-DMN group (DAF, p < 0.01; CD59, p < 0.0001). Within each genotype of the CR1 gene, the E-CR1 level was significantly lower in the DMN group than in the non-DMN group and healthy individuals (non-DMN, p < 0.01; healthy individuals, p < 0.05). The serum-soluble CR1 level was significantly higher in the DMN group than non-DMN group and control group (p < 0.01 each). However, soluble CR1 did not correlate with E-CR1. Conclusion: Acquired loss of E-CR1 was found among HD patients with DMN. From the viewpoint of host defense, it may be a prognostic factor.

Low CR1 (C3b Receptor) Level on Erythrocytes Is Associated with Poor Prognosis in Hemodialysis Patients

“…Patients with diabetic nephropathy have various complications and are susceptible to infection. The acquired loss of E-CR1 in HD patients with diabetic nephropathy was also demonstrated in our previous study [13]. We hypothesize that when E-CR1 expression is low in HD patients with chronic anemia in spite of rEPO treatment, the host defense in these patients may be compromised.…”

“…Low CR1 on erythrocytes in several diseases was recognized as both inherited and acquired [13, 18]. E-CR1 is also reduced in chronic infection, particularly AIDS [19].…”

An analysis of functional activity via the three complement pathways during hemodialysis sessions: a new insight into the association between the lectin pathway and C5 activation

“…Our previous studies suggest that the complement system has important roles in HD patients [ 4 , 7 , 11 – 13 ]. This is the first study investigating the kinetics of the FCA of the three complement pathways simultaneously during HD.…”

Alternative Complement Pathway in Schizophrenia

“…It consists of more than 20 circulating proteins and a similar number of cell-surface receptor and regulatory proteins [1][2][3]. It is a complex cascade involving proteolytic cleavage of serum glycoproteins often activated by cell surface membrane receptors, which specifically bind complement fragments and have been described in various cells, including, epithelial and muscle cells, erythrocytes and different types of leukocytes [4][5][6][7][8][9][10][11][12]. This cascade ultimately results in induction of the inflammatory response, phagocyte chemotaxis, opsonization of apoptotic and necrotic cells, facilitating their recognition, clearance and lysis.…”