Iron metabolism and the role of the iron-regulating hormone hepcidin in health and disease

Daher, Raed; Manceau, Hana; Karim, Zoubida

doi:10.1016/j.lpm.2017.10.006

Cited by 81 publications

(79 citation statements)

References 71 publications

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“…This phenomenon has been previously described by Daher et al, who reported that hepcidin levels were more affected by iron deficiency than by inflammatory activity of the disease. 10 The positive correlation of follow-up serum hepcidin levels with CRP and ferritin and negative correlation with sTfR/log(ferritin) in the CD group suggest that hepcidin may serve as a marker integrating both chronic inflammation and iron deficiency in patients with CD.…”

Section: Discussionmentioning

confidence: 92%

“…The fact that serum hepcidin levels in the UC group did not change significantly while the haemoglobin levels increased supports the hypothesis that iron deficiency predominates over the inflammatory activity in the pathogenesis of anaemia in these patients. This phenomenon has been previously described by Daher et al ., who reported that hepcidin levels were more affected by iron deficiency than by inflammatory activity of the disease . The positive correlation of follow‐up serum hepcidin levels with CRP and ferritin and negative correlation with sTfR/log(ferritin) in the CD group suggest that hepcidin may serve as a marker integrating both chronic inflammation and iron deficiency in patients with CD.…”

Section: Discussionmentioning

confidence: 98%

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Changes in serum hepcidin levels in children with inflammatory bowel disease during anti‐inflammatory treatment

Karásková

Volejnikova

Holub

et al. 2019

J Paediatrics Child Health

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Aim The aim of this study was to compare changes in serum hepcidin levels in paediatric patients with inflammatory bowel disease during therapy and correlate them with markers of iron metabolism, inflammation and type of treatment. Methods Children with newly diagnosed Crohn's disease (CD) and ulcerative colitis (UC) were included in this longitudinal study. Blood and stool samples were collected to assess levels of serum hepcidin and markers of iron metabolism parameters and inflammation. The parameters were examined before treatment (baseline levels) and compared with levels in the follow‐up period during maintenance therapy (mean follow‐up of 39 months after diagnosis). Results Patients with CD (n = 30) had higher serum hepcidin levels (expressed as a median and interquartile range) at diagnosis than subjects with UC (n = 13). These levels significantly decreased during the follow‐up (from 36.5 (11.5–79.6) to 2.1 (0.9–6.7) ng/mL). In contrast, no significant serum hepcidin level changes were observed in the UC patients (5.4 (3.4–16.6) vs. 4.8 (0.9–8.1) ng/mL). While hepcidin level changes correlated with disease activity and inflammatory parameters (erythrocyte sedimentation rate, C‐reactive protein), in CD patients, they correlated only with serum iron levels in patients with UC. Biological therapy was accompanied by a significant decrease in C‐reactive protein and interleukin‐6 compared to conventional anti‐inflammatory therapy in CD patients. Conclusions Children with CD had higher serum hepcidin levels on diagnosis compared to subjects with UC. During an anti‐inflammatory therapy, serum hepcidin decreased in the CD group but remained consistently low in children with UC.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 98%

Changes in serum hepcidin levels in children with inflammatory bowel disease during anti‐inflammatory treatment

Karásková

Volejnikova

Holub

et al. 2019

J Paediatrics Child Health

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“…Iron metabolism is a closed system, critically regulated by hepcidin without any excretory mechanisms for excess iron. As a result, iron levels in ESRD patients chronically treated with IV iron products may exceed their ongoing blood losses, exposing them to an increased risk of positive iron balance . These twin risks of iron deficiency and iron overload must be closely monitored .…”

Section: Introduction and General Remarksmentioning

confidence: 99%

“…As a result, iron levels in ESRD patients chronically treated with IV iron products may exceed their ongoing blood losses, exposing them to an increased risk of positive iron balance. 3,8,9 These twin risks of iron deficiency and iron overload must be closely monitored. 3 Iron overload was considered exceptional in the ESA era, but is now recognized as a potential clinical issue.…”

Section: Introduction and General Remarksmentioning

confidence: 99%

When should iron supplementation in dialysis patients be avoided, minimized or withdrawn?

Rostoker

2018

Seminars in Dialysis

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Parenteral iron is used to restore the body's iron pool before and during erythropoiesis-stimulating agent (ESA) therapy; together these agents form the backbone of anemia management in end-stage renal disease (ESRD) patients undergoing hemodialysis. ESRD patients receiving chronic intravenous iron products, which exceed their blood loss are exposed to an increased risk of positive iron balance. Measurement of the liver iron concentration (LIC) reflects total body iron stores in patients with secondary hemosiderosis and genetic hemochromatosis. Recent studies of LIC in hemodialysis patients, measured by quantitative MRI and magnetic susceptometry, have demonstrated a high risk of iron overload in dialysis patients treated with IV iron products at doses advocated by current anemia management guidelines for dialysis patients. Liver iron overload causes increased production of hepcidin and elevated plasma levels, which can activate macrophages of atherosclerotic plaques. This mechanism may explain the results of 3 long-term epidemiological studies which showed the association of excessive IV iron doses with increased risk of cardiovascular morbidity and mortality among hemodialysis patients. A more physiological approach of iron therapy in ESRD is needed. Peritoneal dialysis patients, hemodialysis patients infected with hepatitis C virus, and hemodialysis patients with ferritin above 1000 μg/L without a concomitant inflammatory state, all require specific and cautious iron management. Two recent studies have shown that most hemodialysis patients will benefit from lower maintenance IV iron dosages; their results are applicable to American hemodialysis patients. Novel pharmacometric and economic approaches to iron therapy and anemia management are emerging which are designed to lessen the potential side effects of excessive IV iron while maintaining hemoglobin stability without an increase in ESA dosing.

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“…Interestingly, there is another outer membrane protein termed FrpB3, which has not been investigated. Finally, it has been observed that the presence of H. pylori can cause anemia in its host, which indicates its enormous capacity of this bacterium to acquire iron from human sources [20,21].…”

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of a Family of Outer Membrane Proteins of Helicobacter pylori, which Scavenge Iron from Human Sources

González-López¹,

Sánchez-Cruz²,

Olivares-Trejo³

2019

J Bacteriol Parasitol

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Introduction:Helicobacter pylori is a gram-negative spiral bacterial, it has been associated with peptic ulcers, gastritis, duodenitis, and it is believed to be the causative agent of gastric cancer. The sources such as human lactoferrin, haem and haemoglobin can support the H. pylori growth. However, is still not fully understood how the process of iron acquisition occurs. An in silico analysis has shown that H. pylori genome has a family of three outer membrane proteins regulated by iron (FrpB). Two of them: FrpB1 and FrpB2 were purified as recombinant proteins and their haem-or haemoglobin-binding capability was demonstrated. Unfortunately, the last protein of the family (FrpB3) has not been investigated. Methods: In this work FrpB3 was purified by haem-affinity chromatography and its capacity of haem-binding was analyzed. This protein was identified by mass spectrometry and its expression was quantified by real time technique under different human iron sources. This expression was compared with FrpB1 and FrpB2. The FrpB3 structure was analyzed by 3D model to view the motifs necessary for Hb-binding, and also was compared with FrpB1 and FrpB2 structures. Results: The protein identified was FrpB3, its respective gene was overexpressed with haemoglobin. FrpB1 was overexpressed with haem, while FrpB2 was induced in presence of haem and also haemoglobin. Both 3D models showed that they are structurally conserved because they have the typical barrel structure, which is inserted in membrane, also, the motifs necessary for Hb-binding were identified in all the structures. Conclusion: H. pylori expresses FrpB1, FrpB2 and FrpB3 proteins to scavenge iron and they are regulated according to availability of iron source, maybe in order to withstand the extreme environment present in the stomach. Our overall results represent the effort to explain the importance of iron acquisition.All human pathogens bacteria require iron for their metabolism and survival [7]. They need iron to catalyze several metabolic processes such as respiratory chain [8] and infectious processes [9]. However, in the human, free iron source is insufficient for J o u rnal of B a c te rio logy & P a ra sitolo g y Citation: González-López MA, Sánchez-Cruz C, Olivares-Trejo JJ (2019) Identification and characterization of a family of outer membrane proteins of Helicobacter pylori, which scavenge iron from human sources. J Bacteriol Parasitol. 10:355. 45. Elloumi H, Sabbah M, Debbiche A, Ouakaa A, Bibani N, Trad D, et al. Systematic gastric biopsy in iron deficiency anaemia. Arab J Gastroenterol. 2017;18(4):224-227.González-López MA et al.

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Iron metabolism and the role of the iron-regulating hormone hepcidin in health and disease

Cited by 81 publications

References 71 publications

Changes in serum hepcidin levels in children with inflammatory bowel disease during anti‐inflammatory treatment

Changes in serum hepcidin levels in children with inflammatory bowel disease during anti‐inflammatory treatment

When should iron supplementation in dialysis patients be avoided, minimized or withdrawn?

Identification and Characterization of a Family of Outer Membrane Proteins of Helicobacter pylori, which Scavenge Iron from Human Sources

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