Determinants for Iron Overload-Related Disease in Siblings of Probands with Clinically Detected HFE Hereditary Hemochromatosis: The Hemochromatosis Family Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1857-1857
Author(s):  
Esther M.G. Jacobs ◽  
Jan C.M. Hendriks ◽  
Herman G. Kreeftenberg ◽  
Richard A. de Vries ◽  
Joannes J.M. Marx ◽  
...  
Keyword(s):  
Iron Overload ◽  
Predictive Value ◽  
Serum Iron ◽  
Alcohol Intake ◽  
Hereditary Hemochromatosis ◽  
High Risk Group ◽  
Early Screening ◽  
Related Disease ◽  
Iron Parameters ◽  
And Gender

Abstract The clinical expression of HFE-associated hereditary hemochromatosis (HH) gen is highly variable and may be influenced by nongenetic factors and coinherited genetic modifiers, complicating early screening options to prevent iron-overload related disease. The aim of this study was to verify the existence of HH-related disease in C282Y homozygous siblings of C282Y homozygous probands with clinically detected HFE-related HH and to identify factors predictive for the iron-related disease within these siblings. To this end, C282Y homozygous (n=110, males n=53) and non-homozygous siblings (n=318, males n=145) of 224 probands were compared for levels of serum iron parameters, and self-reported environmental and lifestyle factors and previously diagnosed HH-related diseases. Compared to non-homozygous C282Y siblings, C282Y homozygous siblings more often mentioned to have been diagnosed with arthropathy (Odds Ratio [OR] 2.76, 95% Confidential Interval [CI] 1.71–4.46) and liver disease (OR 2.90, 95%CI 1.27– 6.62). Using multivariate logistic regression modelling, genotype (OR 2.29, 95%CI 1.04– 5.02), age (OR 1.07, 95% CI 1.04–1.09) and gender (OR 1.71, 95%CI 1.04–2.80) were found predictive for the development of iron-associated organ disease. With genotype in the model, there was neither an additive predictive value of the serum iron parameters, nor of body mass index (BMI) or alcohol intake. However, when the predictive value of the iron parameters was analyzed in siblings above 55 yrs, the input of the serum ferritin levels was also significant, with a less prominent influence of gender. In conclusion, our results show that the prevalence of hemochromatosis-attributed morbid conditions is increased in the C282Y homozygous siblings compared to their non-homozygous counterparts. Results furthermore suggest that age and gender, but not BMI and alcohol intake, add to the identification of C282Y homozygous siblings most at risk to develop hemochromatosis-associated disease. These findings will be instrumental in the definition of a high-risk group for iron overload-related disease among siblings of clinically detected C282Y homozygous probands and may contribute to the cost-effectiveness of family screening.

Iron Overload in C282Y Heterozygotes: Identification of New Rare HFE Gene Mutants and a Step Strategy for Diagnosis.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1859-1859
Author(s):  
Patricia Aguilar-Martinez ◽  
Severine Cunat ◽  
Fabienne Becker ◽  
Francois Blanc ◽  
Marlene Nourrit ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Status ◽  
Hereditary Hemochromatosis ◽  
Genetic Defect ◽  
Transferrin Saturation ◽  
Hfe Gene ◽  
Compound Heterozygous ◽  
Exon 2 ◽  
High Iron ◽  
Iron Parameters

Abstract Introduction: Homozygozity for the p.Cys282Tyr (C282Y) mutation of the HFE gene is the main genotype associated with the common form of adult hereditary hemochromatosis. C282Y carriers do not usually develop iron overload, unless they have additional risk factors such as liver diseases, a dysmetabolic syndrome or an associated genetic defect. The commonest is the compound heterozygous state for C282Y and the widespread p.His63Asp (H63D) variant allele. However, a few rare HFE mutations can be found on the 6th chromosome in trans, some of which are of clinical interest to fully understand the disorder. Patients and Methods: We recently investigated four C282Y carrier patients with unusually high iron parameters, including increased levels of serum ferritin (SF), high transferrin saturation (TS) and high iron liver content measured by MRI. They were males, aged 37, 40, 42, 47 at diagnosis. Two brothers (aged 40 and 42) were referred separately. The HFE genotype, including the determination of the C282Y, H63D and S65C mutations was performed using PCR-RFLP. HFE sequencing was undertaken using the previously described SCA method (1). Sequencing of other genes (namely, HAMP, HJV/HFE2, SLC40A1, TFR2) was possibly performed in a last step using the same method. Results: We identified three rare HFE mutant alleles, two of which are undescribed, in the four studied patients. One patient bore a 13 nucleotide-deletion in exon 6 (c.[1022_1034del13], p.His341_Ala345>LeufsX119), which is predicted to lead to an abnormal, elongated protein. The two brothers had a substitution of the last nucleotide of exon 2 (c.[340G>A], p.Glu114Lys) that may modify the splicing of the 2d intron. The third patient, who bore an insertion of a A in exon 4 (c.[794dupA],p.[trp267LeufsX80]), has already been reported (1). Discussion: A vast majority of C282Y carriers will not develop iron overload and can be reassured. However, a careful step by step strategy at the clinical and genetic levels may allow to correctly identify those patients deserving further investigation. First, clinical examination and the assessment of iron parameters (SF and TS) allow identifying C282Y heterozygotes with an abnormal iron status. Once extrinsic factors such as heavy alcohol intake, virus or a dysmetabolic syndrome have been excluded, MRI is very useful to authenticate a high liver iron content. Second, HFE genotype must first exclude the presence of the H63D mutation. Compound heterozygozity for C282Y and H63D, a very widespread condition in our area, is usually associated with mild iron overload. Third, HFE sequencing can be undertaken and may identify new HFE variants as described here. The two novel mutations, a frameshift modifying the composition and the length of the C terminal end of the HFE protein and a substitution located at the last base of an exon, are likely to lead to an impaired function of HFE in association with the C282Y mutant. However, it is noteworthy that three of the four patients were diagnosed relatively late, after the 4th decade, as it is the case for C282Y homozygotes. Three further unrelated patients are currently under investigation in our laboratory for a similar clinical presentation. Finally, it can be noted that in those patients who will not have a HFE gene mutant identified, analysis of other genes implicated in iron overload must be performed to search for digenism or multigenism. None of our investigated patients had an additional gene abnormality.

Iron Overload in Children Who Are Treated for Acute Lymphoblastic Leukemia Estimated by Liver Siderosis and Serum Iron Parameters

PEDIATRICS ◽  
2003 ◽  
Vol 111 (1) ◽  
pp. 91-96 ◽  
Author(s):  
P. Halonen ◽  
J. Mattila ◽  
P. Suominen ◽  
T. Ruuska ◽  
M. K. Salo ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Iron Overload ◽  
Serum Iron ◽  
Lymphoblastic Leukemia ◽  
Iron Parameters

Mini-Hepcidins Prevent Iron Overload In A Mouse Model of Hereditary Hemochromatosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 689-689
Author(s):  
Elizabeta Nemeth ◽  
Emilio Ramos ◽  
Peter Ruchala ◽  
Gloria Preza ◽  
Tomas Ganz
Keyword(s):  
Iron Overload ◽  
Knockout Mice ◽  
Serum Iron ◽  
Conflicts Of Interest ◽  
Hereditary Hemochromatosis ◽  
Microcytic Anemia ◽  
Iron Loading ◽  
High Doses ◽  
Biophysical Interactions

Abstract Abstract 689 Mini-hepcidins are synthetic peptide analogues of the hepcidin N-terminus which is crucial for hepcidin interaction with ferroportin. Due to their small size and relative ease of synthesis, mini-hepcidins are better candidates than native hepcidin as therapeutics for the prevention and treatment of iron overload. In our previous studies, the first 9 amino acids of hepcidin (DTHFPICIF) were sufficient for in vitro activity (measured as ferroportin-GFP degradation). We modified the amino acid sequence of hepcidin-9 to improve resistance to proteolysis and to enhance the biophysical interactions with ferroportin. From >70 modified mini-hepcidins, we selected several that were more potent than native hepcidin in vitro, and tested them in mouse models. Bioactivity was assessed by measuring the hypoferremic effect of minihepcidins in C57BL/6 mice 4h after administration. Several minihepcidins administered by intraperitoneal or subcutaneous injection were more potent than the native hepcidin in reducing serum iron. Remarkably, retroinverted mini-hepcidins modified by palmitoylation or bile acid conjugation were active also by gavage. None of the tested mini-hepcidins altered endogenous hepcidin production. We also examined the ability of parenteral minihepcidins to prevent tissue iron loading in hepcidin knockout mice. Daily injections for 12 days completely prevented iron loading of the liver, decreased serum iron and increased splenic iron content. At high doses, minihepcidins were sufficiently potent that they caused iron-restricted microcytic anemia in hepcidin knockout mice. Minihepcidins may be useful for the treatment of human iron overload conditions caused by hepcidin deficiency. Disclosures: No relevant conflicts of interest to declare.

Primary Hemochromatosis in Children: Report of Three Newly Diagnosed Cases and Review of the Pediatric Literature

PEDIATRICS ◽  
1992 ◽  
Vol 90 (1) ◽  
pp. 37-42
Author(s):  
Yigal Kaikov ◽  
Louis D. Wadsworth ◽  
Eric Hassall ◽  
James E. Dimmick ◽  
Paul C.J. Rogers
Keyword(s):  
Iron Overload ◽  
Iron Content ◽  
Serum Iron ◽  
Hereditary Hemochromatosis ◽  
Elevated Serum ◽  
Significant Decline ◽  
Hepatic Iron ◽  
Unexpected Finding ◽  
Newly Diagnosed ◽  
Review Of The Literature

Hereditary hemochromatosis was diagnosed in three asymptomatic siblings following the unexpected finding of elevated serum iron concentrations. This diagnosis was confirmed by hepatic biopsy. Repeated phlebotomies resulted in a significant decline of serum iron and ferritin concentrations and a decrease of hepatic iron content. This report and a review of the literature indicate that the diagnosis of hereditary hemochromatosis must be considered more frequently in childhood. Organ dysfunction from iron overload may be minimized in children by the early commencement of regular phlebotomy.

Hemochromatosis in Italy in the Last 30 Years. Role of Genetic and Acquired Factors.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2003-2003
Author(s):  
Anna Ludovica Fracanzani ◽  
Alberto Piperno ◽  
Luca Valenti ◽  
Mirella Fraquelli ◽  
Sabina Coletti ◽  
...  
Keyword(s):  
Risk Factors ◽  
Iron Overload ◽  
Genetic Background ◽  
Alcohol Intake ◽  
Conflicts Of Interest ◽  
Severe Disease ◽  
Hereditary Hemochromatosis ◽  
Clinical History ◽  
History Of ◽  
Cirrhotic Patients

Abstract Abstract 2003 Poster Board I-1025 Background & Aims Clinical presentation of hereditary hemochromatosis markedly changed in the recent years. The aim of the study was to analyze a large series of consecutive Italian patients with hemochromatosis diagnosed between 1976 and 2007 to define whether the genetic background and the presence of acquired risk factors influenced the severity of iron overload and the natural history of the disease across the years. Methods: A cohort of 452 Italian patients with iron overload, of whom 338 HFE-related (C282Y homozygotes or compound C82Y/H63D heterozygotes, and 114 non-HFE-related, prospectively followed for a median of 112 months. Results: Alcohol intake, smoking habits and iron removed to depletion were similar in patients with and without HFE-related iron overload. HBV (4% and 10% p=0.03) and HCV (9% and 17% p=0.02) infections were more frequent in patients with non-HFE-related iron overload. Seventy-three percent and 61% of the patients with HFE and non-HFE-related disease had no acquired risk factor. Cirrhosis was significantly more frequent in non-HFE patients, independently of the presence of acquired risk factors (p=0.02). Gender, alcohol intake, prevalence of smokers, HCV infection, glucose, lipids, iron-related parameters and prevalence of C282Y/H63D significantly differed across the years. At enrolment cirrhosis was present in 145 cases, being significantly more frequent in the first decade (80%, 47% and 13%, p=0.001). Survival did not differ across the decades in cirrhotic patients, HCC occurring similarly in HFE and non-HFE patients. Conclusion: Patients with HFE and non-HFE related iron overload have comparable iron overload and similar clinical history. Patients, unless cirrhotics at enrolment, diagnosed during the last 10 years have less severe disease and lower prevalence of acquired risk factors, independently of genetic background. Disclosures: No relevant conflicts of interest to declare.

Low-Iron Diet and Chelation Therapy Rescue Severe Atherosclerosis Associated with High Circulating Iron Levels

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 199-199 ◽  
Author(s):  
Francesca Vinchi ◽  
Andreas Simmelbauer ◽  
Sandro Altamura ◽  
Sebastian Spaich ◽  
Richard Sparla ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Iron ◽  
Chelation Therapy ◽  
Hereditary Hemochromatosis ◽  
Transferrin Saturation ◽  
Iron Chelation ◽  
Left Ventricular ◽  
Iron Deposition ◽  
Strong Increase ◽  
Atherosclerosis Progression

Abstract In 1981 Sullivan proposed the "iron hypothesis", which states that iron is detrimental for the cardiovascular system, promoting atherosclerosis progression. Iron levels are increased in hereditary hemochromatosis as well as in iron-loading anemias, such as thalassemia, sickle cell disease and the myelodysplastic syndromes. In the latter iron levels may be further increased due to red blood transfusions. To date it is unclear whether iron overload in these disorders promotes atherosclerosis. Conflicting evidence is provided by epidemiological data and studies in disease models. To study susceptibility to atherosclerosis we analyzed ApoE-null mice crossbred with a mouse model of hereditary hemochromatosis type IV, due to a point mutation in the iron exporter ferroportin that prevents hepcidin binding (Altamura et al., Cell Metabolism 2014). We show that at 6 and 12 months of age hemochromatotic ApoE-null mice show a strong increase in lesion size and numbers compared to ApoE-null mice. The atherosclerotic phenotype positively correlates with increased levels of serum iron and transferrin saturation, as well as with iron deposition in the vascular smooth muscle cells, which cause vascular oxidative stress and vessel stiffness. High circulating iron levels promote circulating LDL oxidation, vascular endothelium activation and permeabilization, nitric oxide consumption and inflammation (increased MCP1 and VEGF). In hemochromatotic ApoE-null mice atherosclerotic plaques show reduced collagen deposition and elevated macrophage numbers as well as lipid content and calcification, suggesting enhanced plaque vulnerability and accelerated disease progression. Consistently, these mice develop compensatory left ventricular hypertrophy, associated with increased left ventricle diastolic volume and area. To reduce iron levels we maintained hemochromatotic ApoE-null mice either on a low iron diet (iron content: <10 ppm) or on iron chelation therapy (Deferiprone 8 ml/kg daily). Both, prolonged maintenance on a low iron diet or iron chelator treatment rescued the severe atherosclerotic phenotype in 6 and 10 month-old mice. Importantly, these treatments significantly lowered serum iron levels and transferrin saturation as well as arterial iron deposition. As a consequence, endothelial activation and pro-inflammatory molecule production are strongly reduced, limiting atherosclerosis progression in these mice. Taken together our data suggest that high circulating iron levels strongly enhance the severity of atherosclerosis, thus indicating that systemic iron overload is a risk factor for cardiovascular disease. Furthermore our results demonstrate the beneficial effects of dietary iron limitation and iron chelation in counteracting iron-induced atherosclerosis progression. These observations have potential implications for pathological conditions associated with elevated systemic iron levels and highlight the importance of maintaining low systemic iron levels in these patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Inhibiting the Immunophilin FKBP12: A Potential Therapeutic Approach to Iron Overload/Low Hepcidin Disorders

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2333-2333
Author(s):  
Mariateresa Pettinato ◽  
Mariam Aghajan ◽  
Alessandro Dulja ◽  
Antonella Nai ◽  
Violante Olivari ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Iron ◽  
Target Genes ◽  
Hereditary Hemochromatosis ◽  
Drug Repurposing ◽  
Type I ◽  
Smad Pathway ◽  
Hepcidin Expression

Abstract Introduction Hepcidin negatively regulates body iron by binding and degrading the iron exporter ferroportin. Its expression is mainly controlled by the liver BMP-SMAD pathway whose activation requires BMP ligands (BMP2 and BMP6), constitutively active BMP type II receptors and the type I receptors ALK2 and ALK3. The co-receptor hemojuvelin (HJV) further potentiates the signaling. Mutations in key genes of the pathway impair hepcidin synthesis in Hereditary Hemochromatosis (HH), one of the most severe form being due to HJV mutations. As current therapies are symptomatic and do not correct hepcidin deficiency, alternative targeted therapies to increase hepcidin production are needed. We have demonstrated that the immunophilin FKBP12 binds ALK2 in hepatoma cells to prevent uncontrolled activation of the BMP pathway in the absence of ligands. We also demonstrated that FKBP12 sequestration by immunosuppressive drugs, such as FK506 (tacrolimus, TAC) or rapamycin, upregulate hepcidin in vitro. The role of FKBP12 is maintained in vivo since acute TAC treatment of wild type (WT) mice increases hepcidin expression (Colucci et al., Blood 2017). The aim of this study is to investigate whether pharmacologic inactivation of FKBP12, by TAC or antisense oligonucleotides (ASO), upregulates hepcidin for therapeutic purposes. Methods Primary hepatocytes isolated from WT, Hjv and Tfr2 KO mice (sv129/j background) were treated with increasing concentrations of TAC. Hepcidin and Id1 expression was investigated by qRT-PCR. Nine-weeks-old Hjv KO male mice were treated for 28 days with TAC (0.37 mg/h) delivered through surgically implanted mini-osmotic pumps. Six-weeks-old WT mice, were treated twice a week for 6 weeks with 50 mg/kg of Fkbp12 or control ASO. Mice were sacrificed and analyzed for iron, CBC, erythropoiesis and liver expression of hepcidin and BMP-SMAD target genes. Results TAC treatment of primary HCs from Hjv KO (Colucci et al., Blood 2018) and Tfr2 KO mice upregulates hepcidin as in WT mice, suggesting that HJV and TFR2 are dispensable for FKBP12-dependent hepcidin regulation and providing the proof of principle for FKBP12 targeting in HH. First, we explored a drug repurposing approach in the severe Hjv KO mice by chronic subcutaneous delivery of suboptimal, non-immunosuppressive TAC doses. Treatment of Hjv KO mice with TAC upregulates hepcidin via BMP-SMAD pathway activation, as assessed by Id1 and Smad7 upregulation. Since TAC also inhibits calcineurin upon FKBP12 sequestration and to avoid potential off-targets effect, FKBP12 was inactivated by ASO. Fkbp12 ASO treatment of WT mice decreases Fkbp12 expression by about 70-80% in liver, spleen and kidney, but not in the bone marrow. Fkbp12 ASO-treated mice exhibit microcytic anemia, decreased serum iron and upregulation of liver BMP-SMAD target genes. However, hepcidin remains inappropriately high considering the low serum iron. Fkbp12 ASO-treated mice show increased spleen immature erythroid precursors and increased expression of erythroferrone (Erfe). This is due to the unexpected effect of FKBP12 on spleen erythropoiesis and likely explains the lack of hepcidin upregulation. Conclusions Chronic TAC treatment in Hjv KO mice, which causes FKBP12 sequestration, improves hepcidin expression via BMP-SMAD pathway and favors spleen iron retention, suggesting that this "drug repurposing approach" may be beneficial for all iron overload disorders exhibiting low hepcidin. ASO-Fkbp12 in WT mice efficiently downregulates hepatic Fkbp12, upregulates the BMP-SMAD pathway but leaves hepcidin unchanged compared to control mice. We hypothesize that this result reflects the concomitant hepcidin inhibition due to decreased serum iron and increased Erfe expression. The latter is a consequence of spleen Fkbp12 reduction in ASO-treated mice, suggesting that a hepatocyte targeting Fkbp12 ASO is required for therapeutic purposes. Since Fkbp12 binds and inhibits ALK2 (Colucci et al., Blood 2017), our in vitro and in vivo data suggest that HJV and TFR2 functionally interact with ALK3 but not with ALK2. Disclosures Aghajan: Ionis Pharmaceuticals, Inc: Employment. Guo:Ionis Pharmaceuticals, Inc: Employment. Camaschella:vifor Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Hepcidin Peptidomimetics - Oral Efficacy in Pre-Clinical Disease Model of Iron Overload

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-48
Author(s):  
Roopa Taranath ◽  
Gregory Bourne ◽  
Jie Zhang ◽  
Brian Frederick ◽  
Tran T Tran ◽  
...  
Keyword(s):  
Mouse Model ◽  
Iron Overload ◽  
Polycythemia Vera ◽  
Serum Iron ◽  
Iron Homeostasis ◽  
Hereditary Hemochromatosis ◽  
Iron Concentration ◽  
Transferrin Saturation ◽  
Private Company ◽  
Liver Iron

Hepcidin peptidomimetics that are orally stable and systemically active will mark a paradigm change in management of blood disorders that exhibit aberrant iron homeostasis (e.g. hereditary hemochromatosis) and in conditions that can be influenced by modulating stressed iron homeostasis (e.g. polycythemia vera). Hepcidin modulates the iron exporter membrane protein ferroportin and is the master regulator of iron homeostasis in the body. Orally bioavailable "Minihepcidins" have been previously shown to be efficacious in lowering serum iron in mice when dosed peroral (PO) (Preza GC et. al., Journal of Clinical Investigation 2011). Here we describe hepcidin mimetic peptides that are metabolically stable in the gastrointestinal tract, systemically absorbed when delivered orally, and pharmacodynamically active in reducing serum iron parameters in pre-clinical models. Further, we also demonstrate improvement in disease parameters in a mouse model for hereditary hemochromatosis. The oral peptides, PN20076 and PN20089, have EC50 of 16.5 nM and 1.39 nM respectively in cell based ferroportin internalization assay (Table 1). In comparison EC50 was 67.8 nM for Hepcidin and 6.12 nM for PTG-300. (PTG-300 is an injectable hepcidin mimetic currently in Phase 2 clinical studies for polycythemia vera and hereditary hemochromatosis.) Oral stability of the peptides was evaluated in a panel of assays, including in vitro matrices simulating the gastric and intestinal conditions, and ex vivo matrices of serum/plasma from different species. Table 1 shows data for peptides PN20018, PN20076 and PN20089. PN20076 demonstrated extended stability in gastric and intestinal conditions, and degradation half-life of &gt;24 hr in mouse plasma and 14.8 hr in rat serum. Based on their stability and potency data from the above battery of screening assays, the peptides were selected for in vivo evaluation in healthy mice to characterize their pharmacodynamic (PD) and pharmacokinetic (PK) properties. PN20076 and PN20089 showed equivalent PD response of reduction in serum iron concentration in wild type mice. After two successive PO doses of PN20076 or PN20089 approximately 24 hr apart, serum iron concentration was reduced from ~30 µM to ~10 µM (group averages), i.e. ~66% reduction, at 4.5 hr post-second dose for both peptides (Fig. 1). At 4.5 hr post-dose, the serum concentration of PN20076 was ~262 nM. PN20076 was further evaluated for its effect in lowering iron overload in a mouse model for hemochromatosis (HFE2-/- with homozygous deletion of hemojuvelin, a positive regulator of hepcidin expression). This mouse model is marked by hyper-absorption of dietary iron, higher transferrin saturation and deposition of excessive iron in liver, all manifestations of aberrant iron homeostasis caused by the genetic disruptions of the hepcidin-iron pathway. Liver iron accumulation was significantly prevented in groups treated with PN20076 once daily (QD) by PO administration for over two weeks, as compared to vehicle treated controls (Fig. 2). The reduction in non-heme iron concentration in liver homogenates (measured using a colorimetric iron assay) was statistically significant in the female group treated with PN20076. We have described orally stable and systemically active hepcidin mimetic peptides and demonstrated oral activity in preventing liver iron overload in hemochromatosis mice. The effective reduction of iron absorption from the diet and the steady state lowering of transferrin-saturation can potentially prevent tissue iron toxicity in hereditary hemochromatosis. Similarly, the sustained reduction of systemic iron levels with an oral hepcidin mimetic to control stressed iron homeostasis should reduce excessive erythrocytosis, a hallmark of polycythemia vera and other congenital and acquired erythropoietic disorders. Disclosures Bourne: Protagonist Therapeutics: Current Employment, Other: shareholder. Zhang:Protagonist Therapeutics: Current Employment, Other: shareholder. Frederick:Protagonist Therapeutics: Current Employment, Other: shareholder. Tran:Protagonist Therapeutics: Current Employment, Other: shareholder. Vengalam:Protagonist Therapeutics: Current Employment, Current equity holder in private company. McMahon:Protagonist Therapeutics: Current Employment, Other: shareholder. Huie:Protagonist Therapeutics: Current Employment, Other: shareholder. Ledet:Protagonist Therapeutics: Current Employment, Other: shareholder. Zhao:Protagonist Therapeutics: Current Employment, Other: shareholder. Tovera:Protagonist Therapeutics: Current Employment, Current equity holder in private company. Lee:Protagonist Therapeutics: Current Employment, Current equity holder in private company. Yang:Protagonist Therapeutics: Current Employment, Other: shareholder. Dion:Protagonist Therapeutics: Current Employment, Current equity holder in private company. Yuan:Protagonist Therapeutics: Current Employment, Other: shareholder. Zemede:Protagonist Therapeutics: Current Employment, Current equity holder in private company. Nguyen:Protagonist Therapeutics: Current Employment, Current equity holder in private company. Masjedizadeh:Protagonist Therapeutics: Current Employment, Current equity holder in private company. Cheng:Protagonist Therapeutics: Current Employment, Current equity holder in private company. Mattheakis:Protagonist Therapeutics: Current Employment, Current equity holder in private company. Liu:Protagonist Therapeutics: Current Employment, Current equity holder in private company. Smythe:Protagonist Therapeutics: Current Employment, Other: shareholder.

scholarly journals Soluble transferrin receptor levels among pregnant women in Port Harcourt, Nigeria

2019 ◽  
Vol 7 (10) ◽  
pp. 3622
Author(s):  
Nyebuchi C. Azubuike ◽  
Kemzi N. Elechi-Amadi ◽  
Ojoye N. Briggs ◽  
Zacchaeus A. Jeremiah
Keyword(s):  
Pregnant Women ◽  
Transferrin Receptor ◽  
Predictive Value ◽  
Serum Iron ◽  
Soluble Transferrin Receptor ◽  
Control Subjects ◽  
Iron Parameters ◽  
The Mean ◽  
Anaemia In Pregnancy ◽  
In Pregnancy

Background: Anaemia in pregnancy is one of the medical problems that affect pregnant women in developing countries. It contributes considerably to the morbidity and mortality in pregnancy especially in areas where malaria is endemic. The concentration of soluble transferrin receptor is a reflection of body iron status. It is therefore, a valuable tool for assessing bone marrow erythropoetic activity and can also be a marker of iron deficiency.Methods: This study evaluated the levels of soluble transferrin receptor in pregnant subjects. A total of 275 pregnant subjects of age 20 to 45 years and 88 age-matched apparently healthy control subjects were involved in this study. Individuals who had severe anaemia, HIV infection, sickle cell disease or Hookworm infestation were excluded from this study. Five millilitres (5ml) of blood were collected from each consenting subject for the analysis of soluble transferrin receptor, haematological parameters and iron parameters using appropriate methods.Results: The mean value of parameters for the study subjects were sTfR( 21.16±9.11 nmol/L), Hb(9.05±1.22 g/dl), TIBC(332.61±80.87 µg/dl), Serum Iron(97.91±39.44 µg/dl), LIBC(239.36±80.52 µg/dl), TS(30.24±11.00 %) while for control subjects were sTfR(18.21±3.77 nmol/L), Hb(12.19±0.66 g/dl), TIBC(261.94±52.49µg/dl), Serum Iron(107.10±34.77 µg/dl), LIBC(155.52±61.25 µg/dl), TS(42.81±18.03 %). The mean sTfR levels in pregnant women was significantly lower (p<0.001) than in control subjects. The pregnant women also had significantly lower values of Hb (p<0.001), serum iron (p=0.038) and TS( p<0.001) values, and significantly higher values of TIBC(p<0.0001) and LIBC(p<0.0001). There were also increases in soluble transferrin receptor levels from first to third trimesters. The sensitivity of sTfR as against Serum iron parameters from this study was 76% while the specificity was 50%. The positive predictive value was 60% while the negative predictive value was 50%.Conclusions: sTfR may be a useful supplementary diagnostic tool in the management of anaemia in pregnancy.

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