Soluble Transferrin Receptor

Measurement of sTfR is used to diagnose iron deficiency in individuals with chronic disease (inflammatory diseases, infections, malignancies), many of whom are anemic.

Anemia of chronic disease and iron deficiency anemia, the most common forms of anemia, are differentiated primarily by estimates of iron status. Standard measures of iron status, such as ferritin, total iron-binding capacity, and serum iron are directly affected by chronic disease. In contrast, soluble transferrin receptor (sTfR) is elevated in iron deficiency but is not appreciably affected by chronic disease. sTfR is elevated in subjects with hyperplastic erythropoiesis (eg, hemolytic anemia, beta-thalassemia, polycythemia, etc) and depressed in subjects with hypoplastic erythropoiesis (eg, chronic renal failure, aplastic anemia, or post-transplant anemia). Transferrin receptor (TfR) is the major mediator of iron uptake by cells. TfR is a transmembrane, disulfide-linked dimer of two identical subunits that binds and internalizes diferric transferrin, thereby delivering iron to the cell cytosol. When a cell needs iron, TfR expression is increased to facilitate iron uptake. Since the major use of iron is for hemoglobin synthesis, about 80% of total TfR is on erythroid progenitor cells. Soluble transferrin receptor arises from proteolysis of the intact protein on the cell surface, leading to monomers that can be measured in plasma and serum. Thus, the concentration of sTfR in plasma or serum is an indirect measure of total TfR. The serum level of sTfR reflects either the cellular need for iron or the rate of erythropoiesis. The concentration of sTfR in plasma or serum is elevated in iron deficiency. The concentration of sTfR in plasma or serum is correlated with erythron transferrin uptake, a ferrokinetic measure of erythropoietic activity. 

Allen J, Backstrom KR, Cooper JA, et al. Measurement of soluble transferrin receptor in serum of healthy adults. Clin Chem. 1998 Jan; 44(1):35-39. PubMed 9550555

Khumalo H, Gomo ZA, Moyo VM, et al. Serum transferrin receptors are decreased in the presence of iron overload. Clin Chem. 1998 Jan; 44(1):40-44. PubMed 9550556

Mast AE, Blinder MA, Gronowski AM, Chumley C, Scott MG. Clinical utility of the soluble transferrin receptor and comparison with serum ferritin in several populations. Clin Chem. 1998 Jan; 44(1):45-51. PubMed 9550557

Skikne BS. Circulating transferrin receptor assay—coming of age. Clin Chem. 1998 Jan; 44(1):7-9. PubMed 9550551