Imbalance of erythropoiesis and iron metabolism in patients with thalassemia

Huang, Yumei; Yu, Lei; Liu, Rongrong; Liu, Jiaodi; Yang, Gaohui; Zhang, Xiang; Liang, Yao; Lai, Yongrong

doi:10.7150/ijms.27829

“…iFGF23 found to be higher in Th patients -although not statistically significant (p = 0.14), implying a decreased iFGF23 cleavage. Studies have shown that EPO levels are increased in Th patients compared to controls, with this increase being more pronounced in transfusion dependent thalassemic patients [34].…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 23 (FGF23) and Klotho Protein in Beta-Thalassemia

Stefanopoulos

¹

,

Nasiri-Ansari

²

,

Dontas

³

et al. 2020

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Derangements in phosphate and calcium homeostasis are common in patients with beta-thalassemia. Fibroblast growth factor 23 (FGF23) is among the main hormones regulating phosphate levels, while several studies underline an interplay between iron (Fe) and FGF23. Herein, we investigated, for the first time, the serum intact molecule (iFGF23) and the carboxyl-terminal fragment (C-FGF23) and Klotho levels simultaneously in patients with beta-thalassemia major receiving iron chelation regimens in comparison to healthy control subjects. We also correlated them with the body iron burden. The observational case-control study included 81 subjects (40 thalassemic patients and 41 healthy controls). Serum iFGF23, C-FGF23 and Κlotho were measured by ELISA. Parathormone, 25-hydroxycholecalciferol, calcium, and phosphorus were measured in blood and/or urine. The degree of hemosiderosis was evaluated by assessing the serum ferritin levels and performing T2* MRI measurements. Serum C-FGF23 levels were significantly lower in patients compared to control subjects (p=0.04), while iFGF23 and Klotho levels did not differ. Serum C-FGF23 levels were negatively correlated with ferritin (r=–0,421, p=0.018), whereas there were no significant correlations of each of the three factors with the iron chelation therapy. Decreased serum C-FGF23 levels were found in βTh patients which may be attributed to inhibition of proteolytic cleavage of iFGF23. Further studies in a greater number of patients will shed more light on the disturbances of the iFGF23, Klotho and C-FGF23 in thalassemia and their possible role in bone disease of such patients.

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“…Iron homeostasis and erythropoietic activities appear to differ between thalassemia types and ethnic groups [23]. The globin chain imbalance effect resulted in chronic hemolytic and then ineffective erythropoiesis (IE), which correlated with the compensatory mechanism for anemia and hypoxia [1,6].…”

Section: Discussionmentioning

confidence: 99%

“…Several previous studies have reported serum hepcidin levels, iron status, and GDF15 levels in multitransfused βthalassemia patients. However, information on these protein expression levels and iron status in newly diagnosed patients with β-thalassemia major is very limited [9,[22][23][24][25]. This study was conducted to analyze the iron status, serum hepcidin, and GDF15 levels in newly diagnosed patients with β-thalassemia major and the correlation between variables.…”

Section: Introductionmentioning

confidence: 99%

Iron Status in Newly Diagnosed β-Thalassemia Major: High Rate of Iron Status due to Erythropoiesis Drive

Susanah

¹

,

Rakhmilla

²

,

Ghozali

³

et al. 2021

BioMed Research International

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Background. Iron overload in severe β-thalassemia is a serious complication that occurs during the course of the disease. Information about the iron status during initial illness with β-thalassemia major seemed to be limited. This study is aimed at analyzing iron status, serum hepcidin, and growth differentiation factor 15 (GDF15) levels in newly diagnosed β-thalassemia major. Methods. A case-control study was performed at Dr. Hasan Sadikin General Hospital, which included 41 children with newly diagnosed β-thalassemia major. Age- and sex-matched controls were enrolled. The subjects had no blood transfusion, had normal liver function, and had no sign of inflammation. The groups were compared in terms of the levels of hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), serum hepcidin, and GDF15 as iron homeostasis parameters. Results. Of the 41 newly diagnosed β-thalassemia major patients, those who were less than 24 months old had significantly lower median Hb levels than controls (5.0 vs. 11.7 g/dL, P < 0.001 ). The median SF and TS levels were significantly higher than those in controls (315.0 vs. 29.0 ng/mL, P < 0.001 ; 70.6 vs. 16.5%, P < 0.001 ), and median hepcidin was at the normal limit, but the value was higher in patients (251.0 vs. 123.1 ng/mL, P < 0.001 ). The median GDF15 level was significantly higher in patients (2,095.3 vs. 342.4 pg/mL, P < 0.001 ). There was a positive correlation between SF-TS, SF-hepcidin, TS-hepcidin, SF-GDF15, TS-GDF15, and hepcidin-GDF15 ( P < 0.001 ). Conclusion. In newly diagnosed β-thalassemia major, an increase in iron status occurred. This may be caused by increased iron absorption due to massive erythropoietic activity, characterized by an increase in GDF15 levels, which does not cause hepcidin suppression. The iron homeostasis response seems to be physiologically indicated by a tendency to increase hepcidin levels.

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“…Homozygous patients are categorized as non-transfusion-dependent thalassemia patients (NTDT, previously beta-thalassemia intermedia) or transfusion dependent thalassemia patients (TDT, previously beta-thalassemia major). It is well-known that NTDT patients are prone to developing severe IO, which has been attributed to ineffective erythropoiesis, and can be seen in the absence of high ferritin levels (ferritin <800ng/mL) [ 38 , 39 , 40 ]. The mechanism connecting erythropoiesis and the dysregulated iron metabolism in NTDT has long been unknown, with the discovery of ERFE being a breakthrough in the understanding of this mechanism [ 26 ].…”

Section: Regulation Of Iron Overload In Rhamentioning

confidence: 99%

“…Based on this, ERFE is currently being investigated as a potential pharmacological target in NTDT [ 28 , 43 ]. Moreover, the increased erythropoietic drive may lead reticulocytosis and increased sTfR levels [ 40 , 44 ]. Due to ongoing hemolysis and insufficient compensation of anemia, EPO levels remain high, further stimulating erythroid output and high ERFE expression.…”

Section: Regulation Of Iron Overload In Rhamentioning

confidence: 99%

The Interplay between Drivers of Erythropoiesis and Iron Homeostasis in Rare Hereditary Anemias: Tipping the Balance

Grootendorst

¹

,

Wilde

²

,

Dooijeweert

³

et al. 2021

IJMS

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Rare hereditary anemias (RHA) represent a group of disorders characterized by either impaired production of erythrocytes or decreased survival (i.e., hemolysis). In RHA, the regulation of iron metabolism and erythropoiesis is often disturbed, leading to iron overload or worsening of chronic anemia due to unavailability of iron for erythropoiesis. Whereas iron overload generally is a well-recognized complication in patients requiring regular blood transfusions, it is also a significant problem in a large proportion of patients with RHA that are not transfusion dependent. This indicates that RHA share disease-specific defects in erythroid development that are linked to intrinsic defects in iron metabolism. In this review, we discuss the key regulators involved in the interplay between iron and erythropoiesis and their importance in the spectrum of RHA.

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Imbalance of erythropoiesis and iron metabolism in patients with thalassemia

Cited by 23 publications

References 41 publications

Fibroblast Growth Factor 23 (FGF23) and Klotho Protein in Beta-Thalassemia

Fibroblast Growth Factor 23 (FGF23) and Klotho Protein in Beta-Thalassemia

Iron Status in Newly Diagnosed β-Thalassemia Major: High Rate of Iron Status due to Erythropoiesis Drive

The Interplay between Drivers of Erythropoiesis and Iron Homeostasis in Rare Hereditary Anemias: Tipping the Balance

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