Soluble transferrin receptor for the evaluation of erythropoiesis and iron status

Abstract

Iron transport in the plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor, the transferrin receptor (TfR). A soluble form of the TfR (sTfR) has been identified in animal and human serum. Soluble TfR is a truncated monomer of tissue receptor, lacking its first 100 amino acids, which circulates in the form of a complex of transferrin and its receptor. The erythroblasts rather than reticulocytes are the main source of serum sTfR. Serum sTfR levels average 5.0 F 1.0 mg/l in normal subjects but the various commercial assays give disparate values because of the lack of an international standard. The most important determinant of sTfR levels appears to be marrow erythropoietic activity which can cause variations up to 8 times below and up to 20 times above average normal values. Soluble TfR levels are decreased in situations characterized by diminished erythropoietic activity, and are increased when erythropoiesis is stimulated by hemolysis or ineffective erythropoiesis. Measurements of sTfR are very helpful to investigate the pathophysiology of anemia, quantitatively evaluating the absolute rate of erythropoiesis and the adequacy of marrow proliferative capacity for any given degree of anemia, and to monitor the erythropoietic response to various forms of therapy, in particular allowing to predict response early when changes in hemoglobin are not yet apparent. Iron status also influences sTfR levels, which are considerably elevated in iron deficiency anemia but remain normal in the anemia of inflammation, and thus may be of considerable help in the differential diagnosis of microcytic anemia. This is particularly useful to identify concomitant iron deficiency in a patient with inflammation because ferritin values are then generally normal. Elevated sTfR levels are also the characteristic feature of functional iron deficiency, a situation defined by tissue iron deficiency despite adequate iron stores. The sTfR/ferritin ratio can thus describe iron availability over a wide range of iron stores. With the exception of chronic lymphocytic leukemia (CLL) and high-grade non-Hodgkin's lymphoma and possibly hepatocellular carcinoma, sTfR levels are not increased in patients with malignancies. We conclude that soluble TfR represents a valuable quantitative assay of marrow erythropoietic activity as well as a marker of tissue iron deficiency. D

Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: A prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index

“…Prior studies have suggested that the sTfR Index may improve the ability to accurately classify anemia in diseases with active inflammation [5,[15][16][17][18]. However, these studies involved single institutions with a limited number of subjects reflecting the specialized patient population at that center, which can introduce possible bias in study outcomes.…”

“…Calculating the sTfR/log ferritin index (sTfR Index) from these two measures provides an estimate of body iron over a wide range of normal and depleted iron stores [11,15]. The sTfR Index thus takes advantage of the reciprocal relationship between two variables influenced by iron deficiency, an increase in sTfR and a decrease in the ferritin concentration.…”

“…The sTfR Index thus takes advantage of the reciprocal relationship between two variables influenced by iron deficiency, an increase in sTfR and a decrease in the ferritin concentration. While sTfR and ferritin measurements are useful in the diagnosis of iron deficiency and in the differential diagnosis of various types of anemia, some reports have suggested that the combination of sTfR and ferritin measurements and the calculation of the sTfR Index improves the ability to accurately classify anemia, particularly in anemia accompanying diseases with active inflammation [5,[15][16][17][18].…”

Hypocholesterolemia in chronic anemias with increased erythropoietic activity

“…STR levels were significantly higher in the high-erythroid-activity group (94 ± 18 nmol/l) compared with the control group (34.05 nmol/l; P < 0.001), but the low-erythroid activity group had similar STR levels as the control group (35.29 ± 17.09 nmol/l; NS). In the absence of iron deficiency, as manifested by the elevated serum ferritin levels, the high STR values reflected high bone marrow erythroid activity [16].…”

The soluble transferrin receptor (TfR)-F-Index is not applicable as a test for iron status in patients with chronic lymphocytic leukemia

“…It is increased not only in ID, but also in diseases with increased erythropoesis (2,7,8). The use of sTfR in lymphoproliferative disorders is particularly tricky, especially in patients with chronic lymphocytic leukemia (CLL).…”