The Soluble Transferrin Receptor (sTfR) test is a specialized blood measurement used to determine a person’s functional iron status. It measures a protein fragment circulating in the bloodstream that reflects the body’s need for iron at the cellular level. This test provides a view into the iron supply available for producing new red blood cells, which is particularly useful when standard iron markers are inconclusive.
Understanding the Transferrin Receptor
The fundamental process of iron uptake is managed by the Transferrin Receptor (TfR), a protein found on the surface of most cells, especially those in the bone marrow that make red blood cells. Iron is transported through the blood bound to transferrin, and the TfR acts as the docking station for this complex. Once bound, the cell internalizes the complex to release the iron for cellular processes.
When the cell needs more iron, it increases the number of TfRs on its surface to enhance iron capture. The soluble transferrin receptor (sTfR) measured by the test is the extracellular portion of the membrane-bound TfR. This piece is cleaved from the cell surface by an enzyme and then circulates freely in the plasma.
The amount of sTfR in the blood is directly proportional to the total concentration of membrane-bound TfR on the cells. An elevated level of sTfR indicates that cells, predominantly red blood cell precursors, are increasing receptor production in an attempt to acquire more iron. This makes the sTfR concentration a reflection of the body’s current demand for iron, particularly for erythropoiesis (red blood cell production).
Differentiating Iron Deficiency from Chronic Disease
The sTfR test is useful for distinguishing between Iron Deficiency Anemia (IDA) and Anemia of Chronic Disease (ACD). Traditional iron markers, such as ferritin (which measures iron storage), become unreliable when inflammation or chronic illness is present. Since ferritin is an acute-phase reactant, its concentration rises in response to inflammation, regardless of the body’s actual iron stores.
Inflammation can cause a high ferritin level, incorrectly suggesting adequate iron stores and masking true iron deficiency. The sTfR test is valuable because its concentration is not significantly affected by inflammation. The sTfR level remains an indicator of functional iron deficiency, reflecting the iron available for hemoglobin production.
For patients with chronic disease and anemia, an elevated sTfR level indicates true iron deficiency is present alongside the chronic condition. A normal sTfR level suggests the anemia is likely due only to chronic inflammation, which interferes with iron utilization. This distinction is important because treatment strategies differ for pure ACD versus combined IDA/ACD.
To enhance diagnostic accuracy, the sTfR test is often combined with the ferritin level to calculate the sTfR/log ferritin ratio, known as the sTfR Index. This ratio helps clinicians manage the diagnostic complexity of coexisting inflammation and iron deficiency. The index is designed to detect iron deficiency even when ferritin is artificially elevated by an inflammatory state.
Interpreting Soluble Transferrin Receptor Test Results
sTfR test results are typically reported in units like milligrams per liter (mg/L), though reference ranges vary between laboratories. Generally, the adult reference range for sTfR is approximately 0.8 to 2.5 mg/L.
An elevated sTfR concentration indicates increased iron demand and is a strong sign of iron deficiency. The body produces more receptors to compensate for the lack of iron, causing more soluble fragments to be shed into the blood. An sTfR value above a cutoff, such as 1.55 mg/L, is often used as a predictor of iron deficiency anemia.
A low or normal sTfR level suggests the body has sufficient iron stores or that red blood cell production is decreased. Low values may occur in conditions involving iron overload, such as hereditary hemochromatosis, or in patients with bone marrow disorders resulting in decreased erythropoiesis.
When the sTfR Index is calculated, a ratio exceeding a threshold (e.g., 1.3 or 1.5) strongly suggests iron deficiency, even if ferritin is elevated due to inflammation. The sTfR test offers a practical method for assessing functional iron status and guiding appropriate treatment decisions.