Introduction:
In the medical field, diagnosing a patient’s condition largely depends on clinical examination followed by laboratory investigations. Laboratory investigations are integral to the diagnostic work-up for a patient’s ailment. The serum transferrin receptor assay is an important investigation to know about the metabolism of iron within the body and associated hematological disorders.
What Is Serum Transferrin?
Transferrin is a transport glycoprotein in the blood. It transports iron in the circulation and delivers it to the required cells. Transferrin is produced by hepatocytes in the liver when there is a need for iron or a depletion of iron sources in the body. This glycoprotein selectively and tightly binds to the oxidized iron form (Fe3+). This binding occurs at specific sites on transferrin molecules, forming a complex known as diferric transferrin (as transferrin can take two oxidized iron forms simultaneously).
What Are Transferrin Receptors?
To receive iron from this bound transferrin complex, there are various receptors on the cell surfaces known as transferrin receptors. This transferrin receptor structurally contains two polypeptide chains united by disulfide bonds. There are two types of transferrin receptors - soluble and bound.
1. Soluble Transferrin Receptors: They are present in the circulating blood and are available in soluble or free form. Soluble transferrin receptors are generated when transferrin receptors are cleaved from the cell membrane or shed from the cell surface. This process occurs naturally as part of the turnover of transferrin receptors on cells.
2. Membrane-Bound Transferrin Receptors: Transferrin receptors 1 and 2 are of two types.
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Transferrin receptor 1 (TfR1), also known as CD71, is the primary receptor for transferrin-bound iron and is expressed ubiquitously, with heightened levels in cells that require high iron demands, mainly erythroid precursor cells in the bone marrow. Upon transferrin binding to TfR1, the complex is taken inside the cell via receptor-mediated endocytosis, allowing cells to acquire iron for essential processes such as DNA synthesis and metabolism.
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While less abundant, transferrin receptor 2 (TfR2) is predominantly expressed in hepatocytes (in the liver) and contributes to regulating and maintaining systemic iron homeostasis.
After iron is taken up by cells from the transferrin-iron complex, transferrin alone is released to circulation, and this released transferrin will be ready for the next cycle of iron uptake. Any problems with the expression and function of transferrin receptors can cause disrupted iron homeostasis.
What Is Serum Transferrin Receptor Assay?
This hematological laboratory investigation is done exclusively to determine the levels of soluble or free transferrin receptors in the serum. This also gives an overview of the total number of cell-bound transferrin receptors. Serum transferrin receptor assay is especially useful in cases where hemoglobin or complete blood cell count gives inconclusive results. This assay aims to understand the body's demand for iron and its use and consumption at the cellular level. Dysfunctional iron metabolism in the body can be diagnosed with this assay.
How Is Serum Transferrin Receptor Assay Performed?
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Blood samples of the suspected patient will be collected and subjected to centrifugation. This gives the liquid portion of the blood (serum) by eliminating the cellular components. The serum will then be evaluated for transferrin receptors available in soluble form.
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Through enzyme-linked immunosorbent assay or chemiluminescent immunoassay, specific antibodies that recognize the presence of transferrin receptors are used to capture soluble transferrin receptors present in the serum sample.
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After the soluble transferrin receptors have been captured, a secondary antibody linked to a detectable marker, such as an enzyme or a fluorescent molecule, is added. This secondary antibody binds to the captured transferrin receptors.
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This aids in quantifying the number of transferrin receptors. The amount of soluble transferrin receptors in the serum sample is determined by measuring the signal produced by the detectable marker.
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This signal will be compared to standard curves generated from known concentrations of soluble transferrin receptor standards.
What Is the Normal Range of Serum Transferrin Receptors?
The normal value of serum transferrin receptors is 0.83 to 1.76 milligrams per liter (mg/L). Other serum proteins, medications, or substances may bind to the assay components. This can lead to erroneous serum transferrin receptor level elevation when the range is generally normal. Also, in the early stages of impaired erythropoiesis or mild iron deficiency anemia, the levels of this receptor may be reduced, which results in a lack of sensitivity. These should be considered before interpreting results regarding serum transferrin receptor assay.
What Are the Indications of Serum Transferrin Receptor Assay?
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When serum ferritin and hemoglobin levels cannot give much insight into the type of anemia, serum transferrin receptor assay is indicated; it can help diagnose iron deficiency anemia. The range of serum transferrin receptors is way high in iron deficiency anemia due to increased erythropoietic activity and heightened demand for iron.
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Elevated levels of serum transferrin receptors suggest iron-restricted erythropoiesis (iron deficiency anemia). In contrast, normal levels indicate anemia unrelated to iron deficiency, such as anemia of chronic disease or hemoglobinopathies.
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Serum transferrin receptor assays are done to monitor one’s response to iron therapy. Decreasing levels of serum transferrin receptors over time indicate improved iron status and erythropoietic activity in response to treatment.
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Increased serum transferrin receptor levels directly indicate increased erythropoiesis. This can help diagnose conditions with elevated erythropoiesis, like hemolytic anemia or distress.
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Patients with kidney disease often exhibit disturbances in iron metabolism due to dysfunctional renal mechanisms. Serum transferrin receptor levels can help assess iron status in such patients and guide the administration of iron therapy as a preventive or therapeutic modality for anemia associated with renal dysfunction.
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Erythropoiesis-stimulating agents are used to increase blood cell production in some individuals, especially those who undergo chemotherapy. Serum transferrin receptor levels can be monitored to assess the response to this erythropoiesis stimulating therapy and ensure optimal iron availability for erythropoiesis without exacerbating iron imbalance.
Conclusion:
The serum transferrin receptor assay exemplifies the role of diagnostic medicines and offers valuable insights into iron metabolism, homeostasis, and associated hematological disorders. Its clinical utility extends beyond the diagnosis of iron deficiency anemia, encompassing a wide range of conditions where disturbances in iron homeostasis play a role.
