Erythropoietin therapy in humans increases erythrocyte expression of complement receptor type 1 (CD35)

Abstract

The expression of complement receptor Type 1 (CR 1, CD35) on erythrocytes (E) is unique to humans and other primates. E-CR1, a C3b/C4b receptor that also acts as cofactor for Factor I, appears to be important in clearing C3/C4-opsonized immune complexes from the circulation, in controlling complement activation in the circulation, and in regulating antibody formation. This study was undertaken to determine whether therapy with recombinant human erythropoietin (rEPO) might increase E-CR1 expression in humans. The rationale is that young erythrocytes express more E-CR1 than old erythrocytes. Thus, conditions that stimulate erythropoiesis should increase E-CR1 expression. The hypothesis that stimulating erythropoiesis by rEPO therapy can increase E-CR1 expression was tested in six anemic chronic hemodialysis (ESRD) patients and five systemic lupus erythematosus (SLE) patients without renal failure. Before the rEPO therapy, three of the SLE patients were anemic and two were not. The ESRD patients were studied before and during 9 or 10 mo of rEPO therapy. The SLE patients were studied before, during, and after 7 mo of rEPO given by sc injection two or three times weekly. It was found that rEPO therapy was associated with a progressive increase in the average number of CR1/E in each of the ESRD patients and in the anemic SLE patients: mean baseline CR1/E was 210 + 50 (SE) for the ESRD patients and 125 ± 35 for the SLE patients. The peak percent increase in mean CR1/E, which was observed after about 4 mo of therapy, was 120 ± 35% in the ESRD patients and 190 ± 30% in the anemic SLE patients (P<0.001 by paired † test comparing baseline with peak CR1/E values). The percent change in CR1/E was correlated with the percent change in hematocrit (r= 0.85; P<0.01). In the two nonanemic SLE patients, rEPO therapy did not result in increased CR1/E. However, in these patients, rEPO therapy could not be given continuously because hematocrit levels rose to above 45%, requiring discontinuation of rEPO. It was concluded that rEPO therapy in anemic humans increases E-CR1 expression. The magnitude of the changes suggests that E-CR1 function could be importantly increased by rEPO therapy.