Introduction
Iron is an important element in several physiological processes and metabolic pathways in the body. Transferrin is a major iron-carrier protein responsible for mediating iron transportation through the plasma. It is mainly produced in the liver, and these glycoproteins are in various body fluids. It may also be produced by the brain (choroid plexus) and other tissues. Transferrin protein contains specific binding sites for two Fe3+ (iron) ions. The main function of transferrin is to supply iron from the absorption centers, such as the white blood cells and duodenum, to all the other tissues. It plays a major role in cell division and erythropoiesis (production of red blood cells). Transferrin is also a part of the innate immune system. It acts as a marker for inflammation as the transferrin levels are reduced during inflammation. Healthcare professionals check serum transferrin levels in conditions such as iron deficiency or hemochromatosis (increased iron accumulation in the body).
What Are Transferrin Receptors?
The transferrin receptor is a membrane receptor (iron-binding protein) found in the plasma. It binds to transferrin and plays a vital role in controlling the iron supply to the cells, thus regulating the level of free iron. The synthesis of the transferrin receptor is controlled by an iron-dependent negative feedback in the cells. Recently, more insight has been obtained about the transferrin receptor physiology and its regulation in iron homeostasis. There are two main types of transferrin receptors: transferrin receptor 1(TfR1) and transferrin receptor 2 (TfR2). These membrane receptors help regulate intracellular iron transport and cell growth. Iron circulates in the plasma until it gets attached to the transferrin receptor on the target cell. These receptor levels may be increased in people with iron deficiency; hence, it aids in evaluating and diagnosing iron deficiency anemia.
What Are the Functions of Transferrin Receptors?
Transferrin receptors are embedded in the surface of the cell membrane and the endosomes. The transferrin receptor's main function is mediating the cellular uptake of iron from transferrin. This involves binding the transferrin to the transferrin receptor, internalizing the transferrin molecule inside an endocytic vesicle by receptor-mediated endocytosis (absorption of external substances by engulfing with cell membrane), and releasing iron from the protein by reducing the endosomal pH. There may be some additional functions of transferrin receptors, but are yet to be recognized. Transferrin receptors are mainly expressed on rapidly dividing cells (normal and malignant), immature erythroid cells, and placental tissue. The receptor abundance is usually regulated by cellular iron status and cell growth. Serum transferrin receptor concentration levels are clinically beneficial as their levels are associated with the total mass of immature erythroid cells. Hence, the transferrin receptor is a gatekeeper in maintaining iron homeostasis, forming the basis for utilizing the transferrin receptor as a diagnostic tool.
What Is the Role of Transferrin Receptors in Health and Disease?
The levels of transferrin can vary among individuals and between males and females. The reference range of transferrin receptors in males is 2 to 5 mg/L; in females, it ranges from 1.9 to 4.4 mg/L (milligrams per liter). Variations within the reference range indicate normal physiology, whereas elevated levels suggest iron-deficiency anemia. Reduced transferrin receptor levels can be seen due to protein malnutrition, iron overload (the binding site of transferrin is highly saturated with iron), or a transferrinemia (genetically absent transferrin receptor). Therefore, transferrin receptor level is useful in diagnosing anemia and facilitates deciding on adequate treatment. When done along with other diagnostic tests in an anemia panel, such as iron, ferritin, folate, vitamin B12, and lactate dehydrogenase (LDH), the type of anemia can also be determined based on the transferrin receptor levels. The histochemical analysis of the transferrin receptor serves as an additional tool in differentiating malignancy (cancerous growth) and normal cell growth. Also, it provides additional information regarding the biological behavior of tumor cells.
What Is the Clinical Significance of the Transferrin Receptor?
Iron represents 45 to 55 mg/kg (milligram per kilogram) body weight in adults, and approximately 60 to 70 percent of total body iron is present in the hemoglobin. Iron deficiency is one of the most common nutritional deficiencies in the world, and about 15 to 20 percent of the population suffers from iron deficiency anemia. Along with anemia, iron deficiency can also cause cognitive impairment (confusion or memory loss), developmental delay, and psychomotor issues. It can also increase the susceptibility to infectious diseases or other medical conditions. Therefore, to assess the individual's iron status, tests such as serum iron levels, serum ferritin, iron binding capacity (IBC), and transferrin saturation are performed.
The liver produces transferrin to regulate the iron level when the systemic iron levels are reduced. Transferrin removes the iron stored in the liver and transports it to other body parts through the circulating blood. Transferrin receptor level is increased when the intracellular iron concentration is low. High transferrin levels signify low iron in the body due to less iron binding to transferrin. It results in a high circulation of non-bound iron transferrin and suggests iron deficiency anemia. Transferrin receptor testing can also be used to evaluate microcytic anemia (small red blood cells) and is beneficial in distinguishing between iron deficiency anemia and anemia due to chronic disease or inflammation. Reduced transferrin levels are mainly seen in infections, malignancy, liver damage, and kidney injury. Establishing serum transferrin receptor levels also helps assess the body's iron stores during pregnancy and neonates. Therefore, it is a useful clinical parameter in assessing anemia and erythropoiesis.
Conclusion
Transferrin receptor is an iron-binding glycoprotein present in the plasma and plays an important role in iron homeostasis. Its main function is to mediate the cellular uptake of iron from transferrin. The synthesis or production of transferrin receptors is regulated by the cellular iron levels. The entire spectrum of iron in the body can be determined by measuring the serum ferritin and serum transferrin receptor levels. Assessing iron status and erythropoietic activity by the circulating transferrin receptor has proved valuable in differentiating iron deficiency anemia from anemias due to other conditions.
