Erythroblast iron metabolism and serum soluble transferrin receptor values in the anemia of rheumatoid arthritis

Abstract

Objectives. We have investigated in vitro erythroblast iron metabolism in the anemia of rheumatoid arthritis (RA). We also have examined the results in relation to bone marrow iron status in an attempt to explain the reported difference between serum soluble transferrin receptor (sTfR) values in anemia of chronic disease (ACD) and iron deficiency anemia (IDA) in patients with RA. Methods. Bone marrow was examined in 29 anemic patients with RA, 9 healthy volunteers, and 6 patients with simple IDA. High purity erythroblast fractions were prepared from these bone marrow samples. Erythroblast surface TfR expression and iron uptake was assessed in vitro using 125I-transferrin (Tf) and 59Fe-Tf, respectively. The efficiency of erythroblast surface TfR function for Tf-iron uptake was determined by relating total iron uptake at 4 hours to surface TfR number. Serum sTfR values were measured for the RA anemia group, which was subdivided as RA-ACD (marrow iron present) or RA-IDA (marrow iron absent) on the basis of visible reticuloendothelial (RE) marrow iron stores. Results. High purity (87 ± 5%) erythroblast fractions were obtained from 35 of the 44 marrow samples. Erythroblasts obtained from patients with simple IDA showed a significant increase in surface TfR expression (P = 0.0003) and Tf-iron uptake (P = 0.001). RA anemia also led to a significant increase in erythroblast Tf-iron uptake (P = 0.016). This increase was not associated with an increase in surface TfR expression (P = 0.5), but was seen to occur as a result of a significant increase in the efficiency of surface TfR for Tf-iron uptake (P = 0.027). Within the RA anemia group, the increase in erythroblast Tf-iron uptake at 4 hours was more evident for RA-IDA (3.96 ± 1.73 versus 1.66 ± 0.66; P = 0.03) than for RA-ACD (2.69 ± 1.18 versus 1.66 ± 0.66; P = 0.057). This additional erythroblast response to absent RE iron stores led to a highly significant difference in serum sTfR values between RA-IDA and RA-ACD (40.2 ± 14.0 versus 23.9 ± 5.3 nmoles/liter; P = 0.001) Conclusions. An increase in erythroblast surface TfR efficiency for Tf-iron uptake compensates for the low plasma iron levels associated with anemia in RA and helps to maintain RA erythroblast iron uptake. With adequate RE iron stores, this increased efficiency limits intracellular iron deprivation and consequently reduces the need to increase surface TfR expression. As a result, serum sTfR levels in RA-ACD remain within the normal range. RA erythroblasts, however, are still able to respond to any additional worsening of the iron supply caused by absent RE iron stores. This additional response causes the highly significant increase in serum sTfR values seen between RA-IDA and RA-ACD.