body iron
Recently Published Documents


TOTAL DOCUMENTS

458
(FIVE YEARS 42)

H-INDEX

56
(FIVE YEARS 5)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 761-761
Author(s):  
Maciej W. Garbowski ◽  
Manuel Ugidos ◽  
Alberto Risueño ◽  
Rajasekhar N.V.S. Suragani ◽  
Jeevan K. Shetty ◽  
...  

Abstract Introduction: Luspatercept inhibits select ligands of the TGF-β superfamily implicated in thalassemic erythropoiesis and promotes late-stage erythroid maturation (Suragani RN, et al. Nat Med 2014;20:408-414). This leads to greater red blood cell (RBC) output from thalassemic marrow and reduces transfusion dependence in TDT (Cappellini MD, et al. N Engl J Med 2020;382:1219-1231). The underlying mechanisms for this clinical outcome are not well understood in a syndrome involving significant iron overload and cyclical stimulation of erythropoiesis between transfusions. Here we report novel physiological and clinical insights from a BELIEVE trial (NCT02604433) biomarker analysis, which demonstrate that hepcidin and erythropoietic changes in TDT lead to iron redistribution from macrophages to hepatocytes on luspatercept. Methods: 336 TDT patients ≥ 18 years of age who took part in the BELIEVE study, a multicenter, randomized, double-blind, placebo-controlled phase 3 trial (Cappellini et al. 2020), were randomized 2:1 to receive luspatercept or placebo subcutaneously every 21 days for 48 weeks. This ethically approved study was conducted in accordance with the Declaration of Helsinki. Patients provided written informed consent. Transfusion iron loading rate (ILR) was calculated assuming 1 unit = 200 mg Fe. Liver iron content (LIC) was measured by R2 MRI and R2* MRI, and total body iron stores by Angelucci formula. Serum was assayed for ferritin (SF) nephelometrically (Covance lab), and hepcidin, erythroferrone (ERFE), growth differentiation factor (GDF)15, and transferrin receptor (sTfR1) by ELISA at Intertek (San Diego, CA). Median and interquartile ranges are shown; P value < 0.05 was deemed significant. Results: Within 48 weeks on luspatercept, transfusion iron loading fell by 1.6 g (8 RBC units, ILR difference −0.08 mg Fe/kg/d ± 0.07, range −0.4 to 0.2). Regardless of thalassemic genotype, SF fell by 269.3 ± 963.7 and earliest at 12 weeks by 103.6 ± 690.3 µg/L (both P < 0.0001), with no change on placebo, indicating reduced macrophage iron. However, despite unchanged chelation exposure, no reduction in LIC (5.7 to 6.7 mg/g dw) or calculated body iron stores (3.6 to 4.2 g, not significant) occurred on luspatercept, even though saved iron loading from transfusion was 44% (1.6 g/3.6 g) of baseline body iron stores. On luspatercept, but not placebo, hepcidin fell by 53%, while erythropoietin (EPO), ERFE, GDF15, sTfR1, and reticulocytes rose by 93%, 51%, 59%, 66%, and 112%, respectively (all P < 0.0001). 71% (120/169) patients with and 47% without (17/36) ILR reduction had negative SF trends (P < 0.0001). In patients with SF reduction on luspatercept, bilirubin and LDH rose 50% and 67% (P < 0.0001) indicating increased RBC hemolysis from residual (effective and ineffective) erythropoiesis. ILR change correlated with changes in EPO, hepcidin, sTfR1, and bilirubin, but not with changes in ERFE, GDF15, reticulocytes, or LDH (Figure A). Hepcidin reduction was related to LIC increase post splenectomy (Figure B), suggesting a role for the spleen in preventing hemolytic iron redistribution to the liver. Decrease in SF thus associates with erythroid iron incorporation (sTfR1), hence RBC production that reduces transfusion needs (falling ILR) but enhances hemolytic rerouting of iron to the liver. In a mixed-effect linear regression analysis, transfusion, LIC, baseline SF, time, and treatment predicted SF changes in a benchmark model. We found high baseline LIC lessens the SF outcome, and hepcidin, EPO, and bilirubin jointly explained 66% of the treatment effect of luspatercept on SF. Conclusions: Luspatercept-increased ERFE, likely as a result of increased production or higher frequency of late-stage erythroblasts, partially reduces hepcidin production. Lower hepcidin mobilizes iron stores to facilitate bulk hemoglobinization, erythropoietic response, and transfusion burden reduction. Luspatercept leads to SF reduction that marks hepcidin-dependent iron egress from macrophage compartment to plasma. This relocated iron, variably utilized by thalassemic erythron, refluxes back to plasma for hepatocyte and extrahepatic iron uptake, or as heme iron shunts into the liver through hemolytic pathways from intramarrow ineffective erythropoiesis or peripheral breakdown of newly made thalassemic RBC. Macrophage to hepatocyte iron redistribution in TDT appears to be a mechanism of luspatercept. Figure 1 Figure 1. Disclosures Garbowski: Imara: Consultancy; Vifor: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy. Ugidos: Bristol Myers Squibb: Current Employment. Risueño: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Suragani: Acceleron Pharma: Current Employment, Current equity holder in publicly-traded company. Shetty: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Vodala: BMS: Current Employment, Other: stock options. Thakurta: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Schwickart: BMS (Celgene): Current equity holder in publicly-traded company, Ended employment in the past 24 months, Other, Patents & Royalties; Exelixis: Current Employment, Current equity holder in publicly-traded company. Porter: Celgene (BMS): Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Vifor: Honoraria, Membership on an entity's Board of Directors or advisory committees; Silence Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Honoraria; Protagonism: Honoraria; La Jolla Pharmaceuticals: Honoraria; bluebird bio, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2010-2010
Author(s):  
Diego Hernando ◽  
Ruiyang Zhao ◽  
Qing Yuan ◽  
Mounes Aliyari Ghasabeh ◽  
Stefan Ruschke ◽  
...  

Abstract Introduction: Excessive accumulation of iron is caused by a variety of conditions, including hereditary hemochromatosis and transfusional hemosiderosis. If untreated, iron overload can lead to damage in those organs where iron accumulates. Therefore, accurate and reproducible evaluation of body iron stores is needed to guide diagnosis, grading, and treatment monitoring of iron overload. While serum ferritin is the simplest means to assess body iron, it is also an acute phase reactant and therefore is not a reliable biomarker of body iron. Liver iron concentration (LIC) is directly and linearly related to total body iron stores. As such, LIC is widely recognized as a useful surrogate biomarker for the evaluation of iron overload. Liver biopsy is limited by its invasive nature and is contraindicated in many patients (eg. thrombocytopenia) due to bleeding risk. Magnetic resonance imaging (MRI) is a standard of care tool to measure LIC. Arguably the most practical method is R2* MRI due to its speed and ease of use, but the cross-vendor reproducibility of R2*-based LIC estimation remains unknown. Therefore, we evaluated the reproducibility and calibration of R2*-based LIC measurement via a single-breath-hold, confounder-corrected R2*-MRI at both 1.5T and 3T, through a multi-center, multi-vendor study. Methods: Four centers (University of Wisconsin-Madison, University of Texas-Southwestern, Johns Hopkins University, and Stanford University) using MRI scanners of different vendors (GE, Philips, and Siemens) participated in this HIPAA-compliant IRB-approved prospective cross-sectional study. This study recruited subjects with known or suspected iron overload from a variety of etiologies, including hereditary hemochromatosis, transfusional hemosiderosis (due to non-malignant or malignant conditions), and chronic liver disease. Subjects with were recruited for same day multiecho gradient-echo MRI for R2* mapping at both 1.5T and 3T (UW, UTSW, Stanford: 3.0T; JHU: 2.89T). R2* maps were reconstructed from the raw multiecho images and analyzed at a single center. Spin-echo MRI were also performed at 1.5T according to a standardized protocol (FerriScan, Resonance Health, Australia) and processed by a commercial algorithm to obtain FDA-approved reference standard LIC estimates. R2*-vs.-LIC calibrations were generated across centers and field strengths using linear regression and compared using F-tests. A predicted 2.89T calibration was interpolated from the 1.5T and 3.0T calibrations, and compared to the measured (JHU) calibration. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy of R2* MRI for detection of clinically relevant LIC thresholds. Results: A total of 200 subjects were recruited and successfully scanned for this study. We confirmed a linear relationship between R2* and LIC. All calibrations within the same field strength (see Figure 1) were highly reproducible showing no statistically significant center-specific differences (F > 3.0461). Pooled calibrations for 1.5T, 2.89T, and 3.0T were generated. At either field strength and for each of the LIC thresholds under consideration (1.8, 3.2, 7.0, 15.0 mg/g), estimated areas under the ROC curve (AUCs) of 0.98 or higher were observed. Discussion and Conclusions: In conclusion, confounder-corrected R2* MRI enables accurate and reproducible quantification of liver iron overload, over clinically relevant ranges of LIC. The data generated in this study provide the necessary calibrations for broad dissemination of R2*-based LIC quantification. Figure 1 Figure 1. Disclosures Hernando: Calimetrix: Current holder of individual stocks in a privately-held company. Pedrosa: Merck: Honoraria; Bayer Healthcare: Honoraria; Health Tech International: Current holder of stock options in a privately-held company. Vasanawala: HeartVista: Current holder of individual stocks in a privately-held company; InkSpace: Current holder of individual stocks in a privately-held company; Arterys: Current holder of individual stocks in a privately-held company. Reeder: Bayer: Research Funding; Pfizer: Research Funding; Calimetrix, LLC: Current holder of individual stocks in a privately-held company; Reveal Pharmaceuticals: Current holder of individual stocks in a privately-held company; Elucent Medical: Current holder of individual stocks in a privately-held company; Cellectar Biosciences: Current holder of individual stocks in a privately-held company; HeartVista: Current holder of individual stocks in a privately-held company.


2021 ◽  
Author(s):  
Jithu Varghese James ◽  
Joe Varghese ◽  
Nikhitha Mariya John ◽  
Jean Christophe Deschemin ◽  
Sophie Vaulont ◽  
...  

Increased body iron stores and inflammation in adipose tissue have been implicated in the pathogenesis of insulin resistance (IR) and type 2 diabetes mellitus. However, the underlying basis of these associations are unclear. In order to assess this, we studied how IR and associated inflammation in adipose tissue developed in the presence of increased body iron stores. Male hepcidin knock-out (Hamp1-/-) mice, which have increased body iron stores, and wild-type (WT) mice were fed a high-fat diet (HFD) for 12 and 24 weeks. Development of IR and metabolic parameters linked to this, insulin signaling in tissue, and inflammation and iron-related parameters in visceral adipose tissue were studied in these animals. HFD-feeding resulted in impaired glucose tolerance in both genotypes of mice. In response to the HFD for 24 weeks, Hamp1-/- mice gained less body weight and developed less IR than corresponding WT mice. This was associated with less lipid accumulation in the liver and decreased inflammation and lipolysis in the adipose tissue in the knock-out mice, than in the WT animals. Fewer macrophages infiltrated the adipose tissue in the knockout mice than in wild-type mice, with these macrophages exhibiting a predominantly anti-inflammatory (M2-like) phenotype. These observations suggest a novel role of hepcidin (central regulator of systemic iron homeostasis) in the development of inflammation in adipose tissue and insulin resistance, in response to a high-fat diet.


2021 ◽  
pp. 1-21
Author(s):  
Samar Hameed ◽  
Ihab A. Naser ◽  
Mohamed A. Ghussein ◽  
Mohammed S. Ellulu

Abstract Objective: This study aims to investigate the association between iron body status and postpartum depression (PPD) among mothers during the postpartum period. Design: This is a Case-Control study. Setting: Governmental primary health care centers in the Gaza Strip, Palestine. Participants: This study involved 300 mothers a month after delivery, with one 150 mothers that were recruited in the Cases group who were diagnosed with PPD based on Edinburgh Postnatal Depression Scale (EPDS) ≥10. The Control group included 150 mothers did not have PPD (EPDS <10). Body iron status represented by the index of sTfR/log Ferritin. Results: Among PPD mothers, 43.3% had low ferritin level vs. 15.3% for controls (P<0.001) and cases vs. controls difference in mean hemoglobin level was -0.61 (95% C.I -0.86, -0.35). The results of the Multiple Logistic Regression reported that there is a statistically significant association between PPD and the body iron status existed, as mothers who suffered from iron deficiency (ID) were three times more likely to have PPD (ORadj 3.25; p = 0.015). Furthermore, the results of the final regression model showed that the other factors that can lead to PPD are; absence of psychological guidance services (ORadj 8.54; p = 0.001), suffering from undesired feeling in the last pregnancy (ORadj 1.77; p = 0.034), in addition to having one of the mental health disorders in the last pregnancy (p = 0.001). Conclusion: Body iron status might be a risk factor for postpartum depression and other possibilities of. reverse causality may worsen the condition.


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1686
Author(s):  
Xiaoyu Wang ◽  
Mingzhen Zhang ◽  
Regina R. Woloshun ◽  
Yang Yu ◽  
Jennifer K. Lee ◽  
...  

Intestinal iron transport requires an iron importer (Dmt1) and an iron exporter (Fpn1). The hormone hepcidin regulates iron absorption by modulating Fpn1 protein levels on the basolateral surface of duodenal enterocytes. In the genetic, iron-loading disorder hereditary hemochromatosis (HH), hepcidin production is low and Fpn1 protein expression is elevated. High Fpn1-mediated iron export depletes intracellular iron, causing a paradoxical increase in Dmt1-mediated iron import. Increased activity of both transporters causes excessive iron absorption, thus initiating body iron loading. Logically then, silencing of intestinal Dmt1 or Fpn1 could be an effective therapeutic intervention in HH. It was previously established that Dmt1 knock down prevented iron-loading in weanling Hamp (encoding hepcidin) KO mice (modeling type 2B HH). Here, we tested the hypothesis that Dmt1 silencing combined with dietary iron restriction (which may be recommended for HH patients) will mitigate iron loading once already established. Accordingly, adult Hamp KO mice were switched to a low-iron (LFe) diet and (non-toxic) folic acid-coupled, ginger nanoparticle-derived lipid vectors (FA-GDLVs) were used to deliver negative-control (NC) or Dmt1 siRNA by oral, intragastric gavage daily for 21 days. The LFe diet reduced body iron burden, and experimental interventions potentiated iron losses. For example, Dmt1 siRNA treatment suppressed duodenal Dmt1 mRNA expression (by ~50%) and reduced serum and liver non-heme iron levels (by ~60% and >85%, respectively). Interestingly, some iron-related parameters were repressed similarly by FA-GDLVs carrying either siRNA, including 59Fe (as FeCl3) absorption (~20% lower), pancreatic non-heme iron (reduced by ~65%), and serum ferritin (decreased 40–50%). Ginger may thus contain bioactive lipids that also influence iron homeostasis. In conclusion, the combinatorial approach of FA-GDLV and Dmt1 siRNA treatment, with dietary iron restriction, mitigated pre-existing iron overload in a murine model of HH.


2021 ◽  
Vol 12 (5) ◽  
pp. 69-74
Author(s):  
Ananya Saha ◽  
Pradip Mukhopadhyay ◽  
Indrajit Nath ◽  
Arun Kumar ◽  
Utpal Kumar Biswas

Background: Diabetes is one of the most common disease which is observed in every household of Indian population. The longevity of the diabetic patients is dependent upon the frequency of complication and comorbidity that they encounter. Serum iron and ferritin, both being the aggravators to the oxidative stress accelerating the development of complications, gives us the reason to venture into the territory exploring the possibility of monitoring the body iron stores and taking prevent measures to control such complication. The current study was designed with an aim to knot the relationship between body iron stores and glycemic control in patients of type-II diabetes mellitus. Aims and Objectives: To measure the levels of serum ferritin, serum Iron, transferrin saturation and HbA1C and finding out the relationship between body iron stores and glycemic control in patients of Type-II Diabetes Mellitus. Materials and Methods: A total of 50 diagnosed cases of type II DM and 50 healthy controls between the age group of 35-65 years were taken following inclusion and exclusion criteria. Body iron stores were assessed by measuring serum ferritin, Serum iron and Transferrin saturation and Glycemic control was assessed by measuring levels of HbA1C. Results: A significant increase in serum ferritin, serum iron and Transferrin saturation (P<0.001) was noted in diabetic patients as compared to controls. There was a positive correlation between serum iron and transferring saturation in the diabetic patients. Conclusion: The co-morbidities and complications in the Diabetic population can be prevented by monitoring Body iron stores as they can significantly contribute to the oxidative stress leading to the complication and decreased life expectancy. Early detection in the abnormality in the body iron store can help us in employing proper measures for a better management of Type-II diabetic patients and thereby improving their survival.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250246
Author(s):  
Reginald Adjetey Annan ◽  
Linda Afriyie Gyimah ◽  
Charles Apprey ◽  
Anthony Kwaku Edusei ◽  
Odeafo Asamoah-Boakye ◽  
...  

Background Iron Deficiency Anaemia (IDA) is reportedly high in pregnant adults and the causes well studied. However, among pregnant teenagers, the levels and associated factors of IDA are not fully understood. Methods In a prospective cohort study among Ghanaian pregnant teenagers, aged 13–19 years, IDA prevalence and associated factors were investigated. Sociodemographic data, household hunger scale (HHS), lived poverty index (LPI), FAO’s women’s dietary diversity score (WDDS) and interventions received during antenatal care (ANC) were obtained from 416 pregnant teenagers in Ashanti Region, Ghana. Micronutrient intakes using a repeated 24-hour dietary recall, and mid-upper arm circumference (MUAC) were determined and blood samples analysed for haemoglobin (Hb), serum levels of ferritin, prealbumin, vitamin A, total antioxidant capacity (TAC), C-reactive protein (CRP), and zinc protoporphyrin (ZPP). Results Anaemia (Hb cutoff <11.0 g/dL) was 57.1%; deficient systemic supply of iron stores (31.4%), depleted body stores of iron (4.4%), inadequate dietary iron intake (94.5%), and inadequate multiple micronutrient intakes (49.5%), were all notable among study participants. Between-subject effects using Generalized Linear Modelling indicated malaria tablet given at ANC (p = 0.035), MUAC (p = 0.043), ZPP (p<0.001), ZPP/Hb ratio (p<0.001) and depleted body iron stores (DBIS) (p<0.001) to significantly affect Hb levels. Pregnant teenagers with a high ZPP/Hb ratio (OR = 9.7, p<0.001, 95%CI = 6.0–15.8) had increased odds of being anaemic compared to those with normal ZPP/Hb ratio. Participants who were wasted (OR = 1.2, p = 0.543, 95%CI = 0.6–2.3), and those with depleted iron stores (OR = 3.0, p = 0.167, 95%CI = 0.6–14.6) had increased odds of being anaemic. Participants who experienced hunger were close to 3 times more likely (OR = 2.9, p = 0.040, 95%CI = 1.1–7.8) for depleted iron stores, compared to those who did not experience hunger. Also, participants with inadequate multiple micronutrients intakes (OR = 2.6, p = 0.102, 95%CI = 0.8–8.4), and those with low serum levels of ferritin (OR = 3.3, p = 0.291, 95%CI = 0.4–29.2) had increased odds of depleted body iron stores. Conclusions IDA is common among pregnant teenagers and the related factors include malaria tablets given at ANC, maternal hunger, maternal MUAC, a deficient systemic supply of iron, depleted body iron stores, ZPP, and ZPP/Hb ratio. Appropriate interventions are urgently needed to address the causes of IDA among pregnant teenagers.


2021 ◽  
Vol 58 (1) ◽  
pp. 48-54
Author(s):  
Fernanda F CORRÊA ◽  
Vera L SDEPANIAN

ABSTRACT BACKGROUND: The treatment of patients with inflammatory bowel disease (IBD) consists of the induction and maintenance remission of the disease. Iron status indicators would be useful for the diagnosis of iron deficiency anemia, whereas the inflammation indicators would be for the diagnosis of chronic disease anemia. OBJECTIVE: To assess body iron status indicators and inflammation indicators during the treatment of IBD, consisted of conventional or infliximab therapy in children and adolescents. METHODS: A case-control study of a sample of 116 individuals, of which 81 patients with IBD, 18 of them receiving conventional therapy, 20 infliximab therapy, and 43 who were in remission of the disease, and 35 healthy (control group) children and adolescents. Iron status and inflammation indicators were investigated at baseline, and 2 and 6 months of both therapies - conventional and infliximab. RESULTS: The mean age was 12.1±4.3 years. At baseline, both groups - conventional therapy and infliximab - presented significant differences in most markers studied compared to the control group. After 2 months of conventional therapy, hemoglobin and serum iron levels were lower than those of the control group; and red cells distribution width (RDW), total iron-binding capacity, transferrin receptor/ferritin ratio, and interleukin-6 were higher than the control group. After 2 months of infliximab treatment, hemoglobin and serum iron levels were lower than those of the control group; and RDW, soluble transferrin receptor, soluble transferrin receptor/ferritin ratio, and interleukin-6 were higher than the control group. After 6 months of conventional therapy, hemoglobin and serum iron levels were lower than those of the control group, and RDW and interleukin-6 were higher than those of the control group. After 6 months of infliximab treatment, the hemoglobin and serum iron levels were lower than the control group, and RDW, soluble transferrin receptor, soluble transferrin receptor/ferritin ratio, erythrocyte sedimentation rate, and platelets were higher than the control group. Regarding patients under treatment for at least one year (remission group), all markers studied, except transferrin, were similar to the control group. CONCLUSION: In conclusion, there were some contradictions among the different body iron status indicators and inflammation indicators at two and 6 months of treatment with conventional and infliximab therapy, however after one year of treatment, as shown by the remission group, all indicators studied, except transferrin, were similar to healthy children and adolescents.


Sign in / Sign up

Export Citation Format

Share Document