Endocytosed tftfr is diverged from lysosometargeted proteins in ee with a t. Soluble transferrin receptor stfr is a truncated extracellular form of the membrane transferrin receptor produced by proteolysis. Recombinant soluble transferrin receptor rstfr 1st who reference reagent type of standard. An early idea was to combine the assay of serum ferritin with a measure of. In this context the multifunctional glycolytic enzyme glyceraldehyde3phosphate dehydrogenase gapdh has been reported as a soluble receptor for transferrin. Tibc is increased in iron deficiency, pregnancy and by oral contraceptive therapy. In this study wemeasured stfr levels in the cases of betathalassemia trait. The tfrc gene encodes the transferrin receptor, which is important for cellular iron uptake.
It may be ordered as an alternative to ferritin when you have a chronic illness andor inflammation is present or suspected. 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. Development of a human soluble transferrin receptor elisa. Pdf soluble transferrin receptor stfr and stfrlog ferritin.
Effects of exercise on soluble transferrin receptor and. Pdf the usefulness of soluble transferrin receptor stfr. Soluble transferrin receptors and iron deficiency, a step. However, stfr levels in some situations could be far below the limit of quantification loq of most assays. Soluble transferrin receptor stfr is a circulating, cleaved form of a membrane receptor protein. Tfr is a homodimeric membrane glycoprotein that binds two molecules of tf. Serum transferrin is an independent predictor of mortality.
Is soluble transferrin receptor a good marker of iron. The cohort was randomly divided into exploratory n 200 and validation sets n 628. Feb 12, 2014 transferrin receptors, which are blood proteins, may be elevated in persons with iron deficiency. 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. Soluble transferrin receptor and erythrocyte protoporphyrin testing, or bone marrow biopsy can be considered if the diagnosis remains unclear. The circulating stfr concentration is proportional to cellular expression of the membraneassociated tfr and increases with increased cellular iron needs and cellular proliferation. Human serum transferrin plays a critical physiological role in cellular iron delivery via the transferrin receptor mediated endocytosis pathway in nearly all eukaryotic organisms. 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. Efficient molecular imprinting strategy for quantitative. Role of soluble transferrin receptor and transferrin receptor.
Although fully glycosylated stfr is secreted into the tissue culture medium. Transferrin receptor is a 760 amino acid, transmembrane glycoprotein composed of two disulfidelinked monomers encoded by the gene tfrc. The transferrin receptor tfr is a homodimeric type ii membrane protein that mediates iron uptake into the cells. Soluble transferrin receptor stfr is a new marker of iron status and erythropoietic activity. 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. Soluble transferrin receptor is elevated in association with hyperplastic erythropoiesis, for example, in patients with haemolytic anaemia or betathalassaemia. An increase in transferrin is seen in iron deficiency anemia. As the tfr transferrin iron complex reaches the cell membrane it is internalized via an endocytic vesicle. Transferrin levels rise with iron deficiency and fall in cases of iron overload. The main sources of the stfr are the precursors of erythropoietic cells in the bone marrow. The serum concentration of stfr reflects the amount of the cellular receptor 1,2.
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. Serum gel tubes should be centrifuged within 2 hours of collection. Serum concentrations of the stfr increase in iron deficiency when there is inadequate iron delivery to the bone marrow and tissues. The existence of a receptor for transferrin iron uptake had been recognized over half a century back. 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.
Human transferrin receptor elisa kit ab217780 abcam. Soluble transferrin receptors are proteins found in blood that can be elevated with iron deficiency. Soluble transferrin receptor, human, in vitro, antibody cat. Transferrin has two ironbinding sites and is largely, but not exclusively, synthesized by the liver. Transferrin receptor tfr expression is regulated by the iron regulatory protein system. After adding the product to the cart by clicking the button below you will see if there is a volume discount available. Soluble transferrin receptor, ferritin, iron deficiency. 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. Pdf use of soluble transferrin receptor tfr for the.
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. It consists of two identical subunits linked by disulfide bridges. It has been included in multivariable blood testing models for the detection of performance enhancing erythropoietin misuse in sport. The transferrin receptor tfr is the plasma membrane protein responsible for the binding and internalization of the major iron transport protein, transferrin.
Tfr1 transferrin receptor 1 in human iron metabolism. However, researchers have been able to identify the dominating role of the transferrin transferrin receptor complex in the internalization of iron. Interpreting indicators of iron status during an acute phase response. Moreover, there is a paucity of data on pediatric reference intervals for stfr and stfrferritin index. Levels of this receptor are increased in irondeficiency anemia. Thus, an efficient sample pretreatment strategy is required. Iron is released from transferrin as the result of the acidic ph in endosome and then is transported to the cytosol by dmt1. Pdf determination of serum soluble transferrin receptor stfr is proposed to distinguish between irondeficiency anemia and anemia of. Targetspecific elisa kits are available from a variety of manufacturers and can help streamline your immunodetection experiments. 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. The usefulness of soluble transferrin receptor stfr in differentiating anemia occurring in young children article pdf available in folia histochemica et cytobiologica 503.
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. The function of the single olinked oligosaccharide near the transmembrane domain of the tfr at amino acid thr 104 is unknown. The stfr median concentrations in our population decreased gradually from the group aged 310 years to the group. 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. Pdf role of soluble transferrin receptor and transferrin. Soluble transferrin receptor conventionally refers to the cleaved extracellular portion of. The significance of soluble transferrin receptors in. Iron is an essential nutrient absorbed from the diet.
To evaluate the effect of different types and volumes of physical activity on stfr concentration, variables of iron status ferritin. 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. Tfr1 is a transmembrane glycoprotein composed of two disulfidelinked monomers joined by two disulfide bonds. Parameters for measuring iron deficiency have been established for decades and have served clinicians in the management of this nutritional disorder. Total iron binding capacity is a measure of the total amount of iron with which plasma can combine. Concentrations of serum stfr are related to iron status and erythropoiesis in the body.
Role of soluble transferrin receptor and transferrin. New cutoff values for ferritin and soluble transferrin. Soluble transferrin receptor an overview sciencedirect topics. A majority of plasma transferrin receptors are derived from the erythroid marrow, and their concentration is determined primarily by erythroid marrow activity. Each monomer binds one holo transferrin molecule creating an irontftfr complex which enters the cell by endocytosis. Tfr is an essential receptor, found on almost all cell types, regulated by intracellular iron concentration, and has a high affiinity for transferrin.
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. 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 an overview sciencedirect topics. In the intracellular compartment, iron dissociates from tfr transferrin complex. The soluble transferrin receptor stfr is a soluble truncated form of the transferrin receptor. Adjusting soluble transferrin receptor concentrations for. Use of soluble transferrin receptor tfr for the diagnosis of iron deficiency anemia ida in cirrhotic patients.
To combine data, individual survey analyses, which accounted for. While decreased levels of circulating soluble transferrin receptor are found in patients with erythroid hypoplasia aplastic anemia, chronic renal failure. Serum transferrin receptor levels in betathalassemia. Serum transferrin receptor levels for the assessment of iron status. Endocytosed transferrin receptors recycle via distinct. Tt and ida to see whether it would be a diagnostic tool for the differentiation of. 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. Soluble transferrin receptor and soluble transferrin recepterferritin index for evaluation of the iron status in elderly patients.
Several iron indicators can be used to detect iron deficiency anaemia ida where confounding comorbidities occurred such as patients with regular hemodialysis. Targeted drug delivery via the transferrin receptormediated. Soluble transferrin receptor as a diagnostic laboratory test. Pdf background several iron indicators can be used to detect iron. The stfr median concentrations in our population decreased gradually from the group aged 310 years to the group aged 2140. The bone marrow still remains the gold standard in the final diagnosis of iron deficiency.
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%. 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. Biological and clinical aspects of soluble transferrin. Soluble transferrin receptor stfr conversion to nmoll, mg. Usually the soluble transferrin receptor values are also low. 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. 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. Elevated soluble transferrin receptor stfr in a patient. Soluble transferrin receptor, human, in vitro, antibody. Soluble transferrin receptor article about soluble. 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. Measurement of ferritin is used for the diagnosis of iron deficiency.
Comparison of the interactions of transferrin receptor and. Effect of glycosylation on the function of a soluble. Proteolysis leads to the soluble form of the transferrin receptor. Pdf the soluble transferrin receptor as a marker of iron. Circulating soluble transferrin receptor according to glucose. Soluble transferrin receptor elisa kits biocompare. Soluble transferrin receptor log ferritin tfrf index, using a cutoff of 5. 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. Soluble transferrin receptor stfr conversion to nmoll.
The transferrin receptor is an integral membrane glycoprotein having a molecular weight of 190 kilodaltons kd. Each of the monomers has an 85 kd cterminal component which can bind an ironladen transferrin molecule. The soluble transferrin receptor as a marker of iron homeostasis in normal subjects and in hferelated hemochromatosis article pdf available in haematologica 901. Assayed interlaboratory controls for the assessment of precision and analytical bias on automated systems. As transferrin expression increases with decrease in iron concentrations,measurementofitssoluble form can be a. A study cohort of 436 apparently healthy children was analyzed to establish reference. 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.
Proteolysis leads to the soluble form of the transferrin. 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. Transferrin receptor tfr is the major mediator of iron uptake by cells. Thus, the concentration of stfr in plasma or serum is an indirect measure of total tfr. Soluble transferrin receptor stfr in serum has been suggested as a marker for breast cancer diagnosis, monitoring and treatment. Immunofluorescence analysis of transferrin receptor monoclonal antibody h68. Soluble transferrin receptor conventionally refers to the cleaved extracellular portion of transferrin receptor 1 that is released into serum. 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. 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. Data from these patients were merged with those from the recently diagnosed type 2. Soluble transferrin receptor stfr had been suggested as an indicator for iron deficiency. If ferritin levels do not rise and the symptoms are bothersome, intravenous iron might be. Abstract the aim of this study was to establish soluble serum transferrin receptor stfr reference limits. Tf remains associated with its receptor after endocytosis and dissociates only after recycling of the complex to the plasma membrane.
The transferrin receptor is comprised of two identical subunits, each composed of 760 aminoacids with a molecular mass of 95 kdaltons. Tibc, transferrin saturation, soluble transferrin receptors. The targeted delivery of a therapeutic compound aims to enhance its circulation and cellular uptake, decrease systemic toxicity and improve. Proteolysis leads to the soluble form of the transferrin receptor stfr. Because serum ferritin is an acutephase reactant and because the inflammatory state may inhibit the mobilization of iron from reticuloendothelial stores, the scenario of. Soluble transferrin receptor and soluble transferrin. In the intracellular compartment, iron dissociates from tfrtransferrin complex.
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. This receptor is a protein dimer of two identical subunits, linked together by two pairs of disulfide bonds. We aimed to study the contribution of the serum soluble transferrin receptor stfr. Soluble transferrin receptor stfr, ferritin, and stfr.
Transferrin receptors are transmembrane, homodimeric proteins that play a role in iron transport, uptake, and storage. Transferrintransferrin receptormediated drug delivery li. 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. 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.
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. We investigated whether serum stfr levels can aid in diagnosis and treatment of iron deficiency anemia ida in children. 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. Transferrin is an ironbinding glycoprotein found in the. Elimination of the olinked glycosylation site at thr 104.
Transferrin is responsible for 50% to 70% of the iron binding capacity of serum. 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. In plasma, the soluble transferrin receptor is present in the form of a complex with transferrin having a molecular weight of approximately 320 kd. Recombinant soluble transferrin receptor rstfr1st who. Soluble transferrin receptors stfr are proteins found in blood that can become elevated in the presence of irondeficiency. Increased levels of transferrin receptors tfr and soluble tfr stfr are reliable indicators of iron deficiency anemia and conditions with enhanced erythropoietic activity.
Transferrin receptor tfr is a carrier protein for transferrin. Epo, soluble transferrin receptor, hematocrit hct and % macrocytes were. 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. The cells were fixed with 4% paraformaldehyde for 10 minutes, permeabilized with 0. Soluble transferrin receptor definition of soluble. As the tfrtransferriniron complex reaches the cell membrane it is internalized via an endocytic vesicle. Transferrin receptors, which are blood proteins, may be elevated in persons with iron deficiency. Nov 26, 2001 abstract the aim of this study was to establish soluble serum transferrin receptor stfr reference limits. Measurement of circulating levels of the receptor are very useful in the diagnosis of iron deficiency in patients who also have anemia. 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. The usefulness of soluble transferrin receptor in the. Upon exposure to the acidic ph of the endosome, iron is.
Transferrin receptor is a nonrtk constitutively recycling receptor and thus can be used as a control to assess rtk specificity of met trafficking. Where exposure to inflammation is high, soluble transferrin receptor stfr. Soluble transferrin receptor an overview sciencedirect. Transferrin and the blood brain barrier wed, 09072016 14. Soluble transferrin receptor and risk of type 2 diabetes. Use of multiple antibiotics in patients with cf is routine. The soluble transferrin receptor stfr has an important role in the regulation of iron by mediating the cellular uptake of transferrin bound iron 2. Patients with sah had diminished serum transferrin but increased transferrin saturation. 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. Also known as cd71 and tfr1, transferrin receptor is necessary to regulate iron transport into cells from transferrin by receptor mediated endocytosis. Serum stfr levels are determined to detect iron deficiency. Furthermore, stfr concentrations have been observed to be significantly higher in obese than in nonobese individuals. Most of the binding capacity is due to transferrin. The tfrcholotransferrin complex is internalized by receptor mediated endocytosis summary by jabara et al.
531 75 950 587 1120 1122 691 1104 1272 1589 633 342 1457 792 1065 139 1482 32 761 1042 294 61 284 262 374 168 759 1294 785 1355 465