The transferrin receptor is an integral membrane glycoprotein having a molecular weight of 190 kilodaltons. It consists of two identical subunits linked by disulfide bridges. Each of the monomers has an 85 kD C‐terminal component which can bind an iron-laden transferrin molecule. Proteolysis leads to the soluble form of the transferrin receptor (sTfR). In plasma, the soluble transferrin receptor is present in the form of a complex with transferrin having a molecular weight of approximately 320 kD. The serum concentration of sTfR is directly proportional to the concentration of the receptor on the membrane.
The uptake of iron by the body's cells is controlled by expression of the transferrin receptor (TfR). If the intracellular iron stores are exhausted - corresponding to a ferritin concentration of less than 12 μg/L - then more TfR is expressed. The affinity of the transferrin receptor to transferrin depends on the latter's loading state. As 80‐95 % of the transferrin receptor molecules are localized on erythropoietic cells, the TfR concentration (and hence also the sTfR concentration) reflects the iron requirement of these cells. When iron deficiency exists, the sTfR concentration in serum rises even before the hemoglobin concentration is significantly depressed. The sTfR concentration can therefore describe the functional iron status, while ferritin reflects the iron storage status. A precise assessment of the iron status can be obtained by determining the sTfR index (= sTfR concentration/Log ferritin concentration).
As - in contrast to ferritin - the concentration of sTfR is not affected by acute-phase reactions, acute liver function disorders or malignant tumors, it is possible to differentiate between anemia of chronic disease (ACD) and iron deficiency anemia (IDA). Elevated sTfR values are also found in polycythemia, hemolytic anemia, thalassemia, hereditary spherocytosis, sickle cell anemia, megaloblastic anemia, myelodysplastic syndrome and vitamin B12 deficiency. Elevated sTfR concentrations occur during pregnancy when there is a deficiency of functional iron. Therapy with rhEPO can be monitored via the sTfR concentration.