Detection of Transferrin - Transferrin Receptor Complex TechNotes

Cells obtain iron from plasma where it circulates in a complex with a carrier protein transferrin (Tf). To be transported into cells, iron loaded Tf is bound to transferrin receptor (TfR), and their complex passes into cells by means of internalization, where iron releases by pH-dependent mechanism. Transferrin receptor is a transmembrane protein that participates in iron transport from plasma into cells. It consists of two identical subunits of 95 kDa linked by two disulfide bonds. Each TfR subunit contains an N-terminal cytoplasmic domain (1-67 amino acid residues), a transmembrane domain (68-88 amino acid residues) and a C-terminal extracellular domain (89-760 amino acid residues).

The main pool of TfR molecules is located on erythroblasts which demand a lot of iron for hemoglobin synthesis. After the erythroid cells have matured, the extracellular part of the TfR molecule is truncated from the cell surface by cleavage of an R100 – L101 bond. TfR released into the blood stream consists of 101-760 amino acid residues of cell TfR and is called soluble (or serum) transferrin receptor (sTfR). The expression of transferrin receptor depends on the concentration of iron in the cellular cytoplasm. The concentration of soluble transferrin receptor (sTfR) has been reported to be proportional to the total amount of cell-associated transferrin receptor. In blood, soluble TfR is completely bound to Tf and circulates as sTfR-Tf complex.

The determination of the sTfR level in blood has become widely used in clinical practice. The normal concentration of sTfR in blood ranges within 2 – 5 μg/ml. An increase in the sTfR level was found in iron deficiency anemia, autoimmune hemolytic anemia, hereditary spherocytosis, b-thalassemia, sickle cell anemia and some others. Soluble TfR is indispensable marker of iron deficiency anemia and is mainly used for the differentiation between iron deficiency anemia (accompanied by an increase in the sTfR level) and anemia of chronic
disease (proceeded at the normal sTfR level). The measurement of Tf is also widely used in diagnosis of anemia together with the determination of sTfR, ferritin and iron concentration in serum. Soluble transferrin receptor and transferrin are measured in plasma and serum by immunoassays based on the specific anti-Tf or anti-TfR antibodies.

Hytest offers anti-TfR and anti-Tf MAbs, allowing detection of TfR, Tf and sTfR-Tf complex in human blood.

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