OK, OK, hematologists lower your hand.  Yes, you've probably ordered soluble transferrin measurements at some point in your life to distinguish between iron deficiency anemia and anemia of chronic disease. You guys (or y'all as we say here in the South-ish) can sit this one out for a bit while the rest of us come up to speed on the subject.

 Receptors are proteins that are typically found embedded in the surface of cells and their role is to recognize and bind things.  Once bound to these things, the receptor may transmit signals to the inside of the cell causing some type of cellular transformation, as in a hormone receptor.  Alternatively, once the receptor binds to its thing, both the thing and the receptor can be brought into the cell and in this way receptors are used as a means of delivering certain cargos to cells; as is true for transferrin receptors.

 As their name implies transferrin receptors recognize and bind transferrin.  But it is not transferrin per se that cells covet, but the iron bound to the transferrin.  Transferrin, as the name "trans-ferrin" implies, plays an important role in transporting iron within the blood.  Under normal circumstances this could be dietary iron taken up from the gut, which is transferred by transferrin to erythroid progenitor cells where it would be used for the synthesis of hemoglobin.  For these precursors to take up iron/transferrin complexes, the progenitors must have transferrin receptors on their surface.  Once internalized, the iron is released from transferrin and used for hemoglobin synthesis.  Iron taken into cells that is not used for specific purposes like hemoglobin production can be stored bound to the protein ferritin.

 As important as transferrin receptors may be on the cell surface, our interest here is on soluble transferrin receptors (because they are easier to measure).  Soluble transferrin receptors are derived from receptors on the cell surface by having the bonds that anchored them to the cell surface cleaved by some unknown assailant.  These soluble transferrin receptors, as far as I know, have no known biological function in the circulation.  Nevertheless, their measurement is used clinically as a substitute for ferritin measurements to monitor iron levels in individuals with chronic inflammation where ferritin measurements are of little value (ferritin measurements of dubious value in monitoring iron levels, sound familiar???).

 Our focus on soluble transferrin receptors arises from a recent publication in the British Journal of Hematology1.  This manuscript addresses a topic of immense importance to transfusion-dependent DBA patients and their families: iron overload and its complications.

 I have discussed the problem of iron overload in transfusion-dependent DBA patients many times in this forum.  We have discussed:

• that iron overload and its complications are a significant cause of morbidity and mortality in DBA patients (April, 2012).
• the basic science underlying iron uptake and disposition in the human body (August, 2013).
• that there appears to be something different about the way DBA patients load and store iron relative to other patients receiving a similar number of transfusions (April, 2014).
• and the need for further understanding of iron loading in DBA patients and whether strategies can be developed to reduce the risks and improve outcomes for transfusion-dependent DBA patients (all of the above).