Clinical Information

Iron uptake into cells is mediated through internalizing iron-transferrin complexes. The iron-transferrin complex binds to transferrin receptors present on the external face of the plasma membrane and is internalized through endosomes with ultimate release of iron into the cytoplasm. Plasma membrane-bound transferrin receptor is released by proteolytic cleavage of the extracellular domain, resulting in the formation of a truncated soluble transferrin receptor (sTfR) that circulates freely in the blood.

The concentration of sTfR is an indicator of iron status. Iron deficiency causes overexpression of transferrin receptor and sTfR levels, while iron repletion results in decreased sTfR levels. While ferritin measurement is the accepted method for assessment of iron deficiency, ferritin is an acute-phase reactant and elevates in response to processes that do not correlate with iron status, including inflammation, chronic disease, malignancy, and infection. sTfR is not an acute-phase reactant and the interpretation of iron status using sTfR measurement is not affected by these confounding pathologies.(1)