Circulating Transferrin Receptor Assay—Coming of Age

Abstract

Transferrin receptors are transmembrane proteins present on the surface of most cells. Under normal circumstances, the iron required for cellular metabolism is acquired via transferrin receptors. Several recent reviews detail the methods of iron acquisition, the intracellular throughput of transferrin receptors, and the controlling mechanisms in the cell‘s quest to acquire and store iron (1)(2)(3). The cells of different organ systems show considerable differences in the concentration of cellular transferrin receptor, the highest concentrations being found in cells of organs with the highest iron requirements, such as the erythroid bone marrow and placenta (4). The concentration of cell surface transferrin receptor is carefully regulated by transferrin receptor mRNA according to the internal iron content of the cell and its individual iron requirements. Iron-deficient cells contain increased numbers of receptor, while receptor numbers are downregulated in iron-replete cells (4)(5). Transferrin receptor was identified in serum (6) after investigators recognized that the molecule was secreted into culture media in reticulocyte and erythroleukemia cell models (7)(8), and the concentrations of secreted receptor were found to correlate with the total receptor content of the cells. Subsequent studies showed that serum concentrations of transferrin receptor increase in iron-deficiency anemia, making it a useful marker in the diagnosis of microcytic anemias (9). Circulating transferrin receptor is a truncated form of tissue receptor (10), produced by proteolytic cleavage of cellular receptor, and for the most part circulates attached to transferrin (11)(12). The reference interval for concentration of circulating receptor varies between different assay systems, depending on the choice of calibrators. In this issue of Clinical Chemistry , the transferrin receptor assay recently approved by the US Food and Drug Administration is described by Allen et al. (13). The calibrators used in this enzyme immunoassay system are …