Clinical Information

Transferrin receptor (TfR) mediates iron uptake by cells. It 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 increases to facilitate iron uptake. Since the major use of iron is for hemoglobin synthesis, about 80% of total TfR is located on erythroid progenitor cells.

Soluble transferrin receptor (sTfR) is the product of the proteolysis of TfR at a specific site in the extracellular domain, which leads to monomers that are measurable in serum. A constant relationship is reported between total TfR and the concentration of sTfR in serum. Thus, the concentration of sTfR in serum is an indirect measure of total TfR.

The concentration of sTfR in serum elevates with iron deficiency and hyperplastic erythropoiesis (eg, hemolytic anemia, beta-thalassemia, polycythemia) and decreases in subjects with hypoplastic erythropoiesis (eg, chronic renal failure, aplastic anemia or post-transplant anemia).

Anemia of chronic disease (ACD) and iron deficiency anemia (IDA), 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 confounded by chronic disease, which leads to equivocal results.

Measurement of sTfR is valuable as an indicator of iron deficiency in individuals with chronic disease (eg, inflammatory diseases and infections) as sTfR is minimally affected by proinflammatory cytokines found in ACD patients, which provides an advantage over serum ferritin in the evaluation of iron status and erythropoiesis.(1,2)