Adjusting soluble transferrin receptor concentrations for. It has been included in multivariable blood testing models for the detection of performance enhancing erythropoietin misuse in sport. As the tfr transferrin iron complex reaches the cell membrane it is internalized via an endocytic vesicle. A major pathway for cellular iron uptake is through internalization of the complex of ironbound transferrin and the transferrin receptor, which is negatively modulated by hfe, a protein related to hereditary hemochromatosis. Soluble transferrin receptor, ferritin, iron deficiency. Soluble transferrin receptor levels may be helpful in distinguishing iron deficiency from anemia of chronic inflammation in cf because, unlike serum ferritin and transferrin, soluble transferrin receptor does not appear to be an acutephase reactant. Patients with sah had diminished serum transferrin but increased transferrin saturation. Pdf soluble transferrin receptor stfr and stfrlog ferritin.
Soluble transferrin receptor conventionally refers to the cleaved extracellular portion of transferrin receptor 1 that is released into serum. Soluble transferrin receptor, human, in vitro, antibody cat. Pdf determination of serum soluble transferrin receptor stfr is proposed to distinguish between irondeficiency anemia and anemia of. Soluble transferrin receptor stfr, one of the main regulators of cellular iron homeostasis, is the truncated form of the tissue receptor that is encoded by the human tfr gene chromosome 3. Soluble transferrin receptor an overview sciencedirect. Transferrin is responsible for 50% to 70% of the iron binding capacity of serum. Current cancer management strategies fail to adequately treat malignancies with multivariable doserestricting factors such as systemic toxicity and multidrug resistance limiting therapeutic benefit, quality of life and complete longterm remission rates. However, stfr levels in some situations could be far below the limit of quantification loq of most assays. Tfr1 transferrin receptor 1 in human iron metabolism.
Tfr is an essential receptor, found on almost all cell types, regulated by intracellular iron concentration, and has a high affiinity for transferrin. The transferrin receptor tfr is a homodimeric type ii membrane protein that mediates iron uptake into the cells. Iron is an essential nutrient absorbed from the diet. The bone marrow still remains the gold standard in the final diagnosis of iron deficiency.
Concentrations of serum stfr are related to iron status and erythropoiesis in the body. Tibc, transferrin saturation, soluble transferrin receptors. Soluble transferrin receptor and soluble transferrin recepterferritin index for evaluation of the iron status in elderly patients. A study cohort of 436 apparently healthy children was analyzed to establish reference. An increase in transferrin is seen in iron deficiency anemia. Recent studies have also suggested that stfr measurements are helpful when predicting the response to erythropoietin in patients with anaemia resultant from chronic renal failure. Epo, soluble transferrin receptor, hematocrit hct and % macrocytes were. Levels of this receptor are increased in irondeficiency anemia. Soluble transferrin receptor elisa kits the elisa enzymelinked immunosorbent assay is a widely used application for detecting and quantifying proteins and antigens from various samples. Targetspecific elisa kits are available from a variety of manufacturers and can help streamline your immunodetection experiments. Abstract the aim of this study was to establish soluble serum transferrin receptor stfr reference limits.
No study has investigated the meaning of high stfr as the only positive marker of iron deficiency anemia ida caused by gastrointestinal tract git bleeding in hospitalized patients. This efficient cellular uptake pathway has been exploited for the sitespecific delivery not only of anticancer drugs and proteins, but also of therapeutic genes into proliferating malignant cells that. Elevated soluble transferrin receptor stfr in a patient. Soluble transferrin receptor elisa kits biocompare. In plasma, the soluble transferrin receptor is present in the form of a complex with transferrin having a molecular weight of approximately 320 kd. Data from these patients were merged with those from the recently diagnosed type 2. Transferrin receptor tfr is the major mediator of iron uptake by cells. Transferrin receptor tfr expression is regulated by the iron regulatory protein system. To evaluate the effect of different types and volumes of physical activity on stfr concentration, variables of iron status ferritin. Pdf use of soluble transferrin receptor tfr for the. Soluble transferrin receptor and soluble transferrin. Tfr is abundant on the surface of many newly formed cells, but the erythroid marrow cells account for 70 to 80 % of the total body tfr content. We aimed to study the contribution of the serum soluble transferrin receptor stfr.
Effects of exercise on soluble transferrin receptor and. Targeted drug delivery via the transferrin receptormediated. Nov 26, 2001 abstract the aim of this study was to establish soluble serum transferrin receptor stfr reference limits. Tt and ida to see whether it would be a diagnostic tool for the differentiation of. A soluble receptor for any ligand could also refer to a molecule present is solution for example a secretory protein which would bind with the target ligand and then effect cellular delivery. Is soluble transferrin receptor a good marker of iron. Biological and clinical aspects of soluble transferrin. Soluble transferrin receptor and erythrocyte protoporphyrin testing, or bone marrow biopsy can be considered if the diagnosis remains unclear. Role of soluble transferrin receptor and transferrin. Usually the soluble transferrin receptor values are also low. Immunofluorescence analysis of transferrin receptor monoclonal antibody h68.
Endocytosed tftfr is diverged from lysosometargeted proteins in ee with a t. In this study wemeasured stfr levels in the cases of betathalassemia trait. In this study, molecularly imprinted polymers mips were developed and coupled with liquid. It may be ordered as an alternative to ferritin when you have a chronic illness andor inflammation is present or suspected. The soluble transferrin receptor as a marker of iron homeostasis in normal subjects and in hferelated hemochromatosis article pdf available in haematologica 901. Dec 01, 2002 the membrane transferrin receptor mediated endocytosis or internalization of the complex of transferrin bound iron and the transferrin receptor is the major route of cellular iron uptake. Serum transferrin receptor levels in betathalassemia. Soluble transferrin receptor and ferritin concentrations were nephelometrically determined by n latex reagent sets bade behring according to the manufacturers instructions after storage of the centrifuged 2600g.
Production of the soluble portion of the transferrin receptor stfr by baby hamster kidney bhk cells is described, and the effect of glycosylation on the biological function of stfr is evaluated for the first time. New cutoff values for ferritin and soluble transferrin. Transferrin is an ironbinding glycoprotein found in the. Most of the binding capacity is due to transferrin.
Soluble transferrin receptor stfr is a truncated extracellular form of the membrane transferrin receptor produced by proteolysis. Serum transferrin is an independent predictor of mortality. The soluble transferrin receptor test is not routine but may be ordered along with or in follow up to other iron tests when you have a normal or nearnormal ferritin level but iron deficiency is still suspected. It is needed for the import of iron into the cell and is regulated in response to intracellular iron concentration. The targeted delivery of a therapeutic compound aims to enhance its circulation and cellular uptake, decrease systemic toxicity and improve. Soluble transferrin receptors and iron deficiency 347 the endosomes acidosomes, and the tftfr complex is returned back to the cell surface, where apo transferrin is released again 41. Transferrin receptor an overview sciencedirect topics. Each monomer binds one holo transferrin molecule creating an irontftfr complex which enters the cell by endocytosis. Several iron indicators can be used to detect iron deficiency anaemia ida where confounding comorbidities occurred such as patients with regular hemodialysis. Measurement of ferritin is used for the diagnosis of iron deficiency. The soluble transferrin receptor stfr has an important role in the regulation of iron by mediating the cellular uptake of transferrin bound iron 2. Soluble transferrin receptor definition of soluble. Soluble transferrin receptor as a diagnostic laboratory test.
Thus, an efficient sample pretreatment strategy is required. However, researchers have been able to identify the dominating role of the transferrin transferrin receptor complex in the internalization of iron. The transferrin receptor tfr is the plasma membrane protein responsible for the binding and internalization of the major iron transport protein, transferrin. Pdf the usefulness of soluble transferrin receptor stfr.
Soluble transferrin receptor conventionally refers to the cleaved extracellular portion of. It consists of two identical subunits linked by disulfide bridges. In the intracellular compartment, iron dissociates from tfr transferrin complex. The usefulness of soluble transferrin receptor stfr in differentiating anemia occurring in young children article pdf available in folia histochemica et cytobiologica 503. Proteolysis leads to the soluble form of the transferrin receptor. Human transferrin receptor elisa kit ab217780 abcam. We investigated whether serum stfr levels can aid in diagnosis and treatment of iron deficiency anemia ida in children. The soluble transferrin receptor stfr is a soluble truncated form of the transferrin receptor. Comparison of the interactions of transferrin receptor and. Because serum ferritin is an acutephase reactant and because the inflammatory state may inhibit the mobilization of iron from reticuloendothelial stores, the scenario of. Transferrin receptors, which are blood proteins, may be elevated in persons with iron deficiency. Upon exposure to the acidic ph of the endosome, iron is.
After adding the product to the cart by clicking the button below you will see if there is a volume discount available. The cohort was randomly divided into exploratory n 200 and validation sets n 628. Development of a human soluble transferrin receptor elisa. Tfr transferrin r the transferrin receptor tfr or tfr1, designated cd71 is a type 2 transmembrane glycoprotein expressed on erythroid progenitors, muscle cells and proliferating cells as a 188 kda disulfidelinked homodimer of 95 kda monomers 1 4. Tfr1 is a transmembrane glycoprotein composed of two disulfidelinked monomers joined by two disulfide bonds. Although fully glycosylated stfr is secreted into the tissue culture medium. Transferrintransferrin receptormediated drug delivery li. Total iron binding capacity is a measure of the total amount of iron with which plasma can combine. The transferrin receptor is an integral membrane glycoprotein having a molecular weight of 190 kilodaltons kd. Soluble transferrin receptor stfr in serum has been suggested as a marker for breast cancer diagnosis, monitoring and treatment. The serum concentration of stfr reflects the amount of the cellular receptor 1,2. The main sources of the stfr are the precursors of erythropoietic cells in the bone marrow. Interpreting indicators of iron status during an acute phase response.
Human transferrin receptor elisa kit ab217780 is a singlewash 90 min sandwich elisa designed for the quantitative measurement of transferrin receptor protein in cit plasma, edta plasma, hep plasma, saliva, serum, urine, and cell culture extracts. Effect of glycosylation on the function of a soluble. Soluble transferrin receptor stfr is a new marker of iron status and erythropoietic activity. Soluble transferrin receptor log ferritin tfrf index, using a cutoff of 5. The stfr median concentrations in our population decreased gradually from the group aged 310 years to the group. Transferrin receptor testing is used to measure the level soluble transferrin receptors, thereby aiding in the evaluation of iron deficiency and in the diagnosis of irondeficiency anemia. Each of the monomers has an 85 kd cterminal component which can bind an ironladen transferrin molecule. An early idea was to combine the assay of serum ferritin with a measure of. Proteolysis leads to the soluble form of the transferrin. Transferrin levels rise with iron deficiency and fall in cases of iron overload. Increased levels of transferrin receptors tfr and soluble tfr stfr are reliable indicators of iron deficiency anemia and conditions with enhanced erythropoietic activity. Elimination of the olinked glycosylation site at thr 104. Feb 12, 2014 transferrin receptors, which are blood proteins, may be elevated in persons with iron deficiency.
The circulating stfr concentration is proportional to cellular expression of the membraneassociated tfr and increases with increased cellular iron needs and cellular proliferation. This test measures the amount of soluble transferrin receptors to help detect and evaluate iron deficiency and aid in the diagnosis of iron deficiency anemia. Moreover, there is a paucity of data on pediatric reference intervals for stfr and stfrferritin index. Tfr is a homodimeric membrane glycoprotein that binds two molecules of tf. Studies evaluating the relationship between soluble transferrin receptor stfr, a biomarker inversely related to body iron stores, and risk of type 2 diabetes mellitus t2dm are scarce and inconclusive. Soluble transferrin receptor article about soluble. This test measures the amount of soluble transferrin receptors within the blood, to help detect and evaluate iron deficiency and aid in the diagnosis of iron deficiency anaemia iron is an essential nutrient absorbed from the diet.
Soluble transferrin receptor is elevated in association with hyperplastic erythropoiesis, for example, in patients with haemolytic anaemia or betathalassaemia. The tfrc gene encodes the transferrin receptor, which is important for cellular iron uptake. It is widely used in mammalian cell cultures for the production of biotherapeutic proteins and vaccines and is also being explored for use as a therapy and targeted. As the tfrtransferriniron complex reaches the cell membrane it is internalized via an endocytic vesicle. Serum concentrations of the stfr increase in iron deficiency when there is inadequate iron delivery to the bone marrow and tissues. To combine data, individual survey analyses, which accounted for. The function of the single olinked oligosaccharide near the transmembrane domain of the tfr at amino acid thr 104 is unknown. Pdf role of soluble transferrin receptor and transferrin.
Tibc is increased in iron deficiency, pregnancy and by oral contraceptive therapy. This study aim was to determine the diagnostic value of stfr and tfrf index and to combine these two markers in detecting ida in rh anaemic. Parameters for measuring iron deficiency have been established for decades and have served clinicians in the management of this nutritional disorder. Use of multiple antibiotics in patients with cf is routine. Soluble transferrin receptor an overview sciencedirect topics. In order to improve the diagnostic accuracy of ferritin or stfr as a standalone marker, the normal cutoff value needed to be increased by 810% and 83%. Soluble transferrin receptors are proteins found in blood that can be elevated with iron deficiency. As transferrin expression increases with decrease in iron concentrations,measurementofitssoluble form can be a. The increasing prevalence of multiple comorbidities among anemic patients with chronic kidney disease has made the use of serum ferritin and transferrin saturation more challenging in diagnosing iron deficiency. If ferritin levels do not rise and the symptoms are bothersome, intravenous iron might be. Recent investigations have demonstrated that the soluble form of the transferrin receptor in human serum is an 85kda fragment of intact receptor containing most of the extracellular domain. Role of soluble transferrin receptor and transferrin receptor.
In this context the multifunctional glycolytic enzyme glyceraldehyde3phosphate dehydrogenase gapdh has been reported as a soluble receptor for transferrin. Soluble transferrin receptor stfr conversion to nmoll, mg. Pdf background several iron indicators can be used to detect iron. Use of soluble transferrin receptor tfr for the diagnosis of iron deficiency anemia ida in cirrhotic patients. Transferrin receptor is a 760 amino acid, transmembrane glycoprotein composed of two disulfidelinked monomers encoded by the gene tfrc. Transferrin receptors are transmembrane, homodimeric proteins that play a role in iron transport, uptake, and storage. Tfr is a transmembrane, disulfidelinked dimer of two identical subunits that binds and internalizes diferric transferrin, thereby delivering iron to the cell cytosol. Transferrin receptor testing is used to measure the level of soluble transferrin receptors, thereby aiding in the evaluation of iron deficiency and in the diagnosis of irondeficiency anemia the reference range of transferrin receptor varies by sex in adults, as follows. Tfr transferrin r the transferrin receptor tfr or tfr1, designated cd71 is a type 2 transmembrane glycoprotein expressed on erythroid progenitors, muscle cells and proliferating cells as a 188 kda disulfidelinked homodimer of 95 kda monomers 14. Efficient molecular imprinting strategy for quantitative. In the intracellular compartment, iron dissociates from tfrtransferrin complex. Soluble transferrin receptor stfr conversion to nmoll.
Iron is released from transferrin as the result of the acidic ph in endosome and then is transported to the cytosol by dmt1. The soluble transferrin receptor stfr has been introduced as a promising new diagnostic tool for differentiating between iron deficiency anemia ida and anemia of chronic disease acd. Pdf the soluble transferrin receptor as a marker of iron. The significance of soluble transferrin receptors in. This receptor is a protein dimer of two identical subunits, linked together by two pairs of disulfide bonds. Measurement of circulating levels of the receptor are very useful in the diagnosis of iron deficiency in patients who also have anemia. This study was aimed to determine the diagnostic value of serum transferrin receptor stfr and transferrin receptor transferrin index tfrf index and to combine these two markers in detecting ida in regular. Circulating soluble transferrin receptor according to glucose. Transferrin receptor tfr is a carrier protein for transferrin. The stfr median concentrations in our population decreased gradually from the group aged 310 years to the group aged 2140. Soluble transferrin receptor stfr is a circulating, cleaved form of a membrane receptor protein.
The best diagnostic parameter for detecting iron deficiency in patients with malignant hemopathies by roc analysis is the soluble transferrin receptor log ferritin index auc 0. A majority of plasma transferrin receptors are derived from the erythroid marrow, and their concentration is determined primarily by erythroid marrow activity. Proteolysis leads to the soluble form of the transferrin receptor stfr. Soluble transferrin receptor stfr had been suggested as an indicator for iron deficiency. Where exposure to inflammation is high, soluble transferrin receptor stfr. The transferrin receptor is comprised of two identical subunits, each composed of 760 aminoacids with a molecular mass of 95 kdaltons. Recombinant soluble transferrin receptor rstfr 1st who reference reagent type of standard. Soluble transferrin receptor and risk of type 2 diabetes.
Human serum transferrin plays a critical physiological role in cellular iron delivery via the transferrin receptor mediated endocytosis pathway in nearly all eukaryotic organisms. Serum transferrin receptor levels for the assessment of iron status. Recombinant soluble transferrin receptor rstfr1st who. Serum stfr levels are determined to detect iron deficiency. Soluble transferrin receptors and iron deficiency, a step. Transferrin receptor is a nonrtk constitutively recycling receptor and thus can be used as a control to assess rtk specificity of met trafficking.
While decreased levels of circulating soluble transferrin receptor are found in patients with erythroid hypoplasia aplastic anemia, chronic renal failure. Thus, the concentration of stfr in plasma or serum is an indirect measure of total tfr. The cells were fixed with 4% paraformaldehyde for 10 minutes, permeabilized with 0. The usefulness of soluble transferrin receptor in the.
Furthermore, stfr concentrations have been observed to be significantly higher in obese than in nonobese individuals. Transferrin has two ironbinding sites and is largely, but not exclusively, synthesized by the liver. Transferrin and the blood brain barrier wed, 09072016 14. Endocytosed transferrin receptors recycle via distinct. Soluble transferrin receptor arises from proteolysis of the intact protein on the cell surface, leading to monomers that can be measured in plasma and serum. Also known as cd71 and tfr1, transferrin receptor is necessary to regulate iron transport into cells from transferrin by receptor mediated endocytosis. The existence of a receptor for transferrin iron uptake had been recognized over half a century back. Transferrin receptor tfr the transferrin receptor tfr is the gateway for transferrin boundiron entering all body cells. It imports iron by internalizing the transferrin iron complex through receptor mediated endocytosis. Soluble transferrin receptors stfr are proteins found in blood that can become elevated in the presence of irondeficiency. Serum gel tubes should be centrifuged within 2 hours of collection. Soluble transferrin receptor, human, in vitro, antibody. Soluble transferrin receptor stfr, ferritin, and stfr. This test measures the amount of soluble transferrin receptors within the blood, to help detect and evaluate iron deficiency and aid in the diagnosis of iron deficiency anaemia.