ERFE regulation in sickle cell disease: complex but promising

Girelli, Domenico; Busti, Fabiana

doi:10.1111/bjh.16527

Cited by 2 publications

(4 citation statements)

References 19 publications

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“…ERFE concentrations were found to be significantly higher in β-thalassemia major patients compared to XLSA patients. This can be attributed to increased severity of ineffective erythropoiesis in β-thalassemia major patients, that results in lower Hb levels and a more frequent need of blood transfusions [7,23]. Therefore, quantification of ERFE might serve as a marker for severity of ineffective erythropoiesis and may eventually be a used in diagnostics of iron loading anemias and to predict the risk of body iron overload in these diseases.…”

Section: Plos Onementioning

confidence: 99%

“…Currently, only one validated in-house monoclonal ERFE enzyme-linked immunosorbent assay (ELISA) has been published [22], and several commercial kits are on the market. However, none is yet routinely available [23] and solely used for research. Our experience in developing assays for the iron-related measurements [24][25][26][27][28][29] has taught us the importance of validation and standardization before using an assay in clinical practice [30][31][32].…”

Section: Introductionmentioning

confidence: 99%

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Differentiating iron-loading anemias using a newly developed and analytically validated ELISA for human serum erythroferrone

et al. 2021

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Erythroferrone (ERFE), the erythroid regulator of iron metabolism, inhibits hepcidin to increase iron availability for erythropoiesis. ERFE plays a pathological role during ineffective erythropoiesis as occurs in X-linked sideroblastic anemia (XLSA) and β-thalassemia. Its measurement might serve as an indicator of severity for these diseases. However, for reliable quantification of ERFE analytical characterization is indispensable to determine the assay’s limitations and define proper methodology. We developed a sandwich ELISA for human serum ERFE using polyclonal antibodies and report its extensive analytical validation. This new assay showed, for the first time, the differentiation of XLSA and β-thalassemia major patients from healthy controls (p = 0.03) and from each other (p<0.01), showing the assay provides biological plausible results. Despite poor dilution linearity, parallelism and recovery in patient serum matrix, which indicated presence of a matrix effect and/or different immunoreactivity of the antibodies to the recombinant standard and the endogenous analyte, our assay correlated well with two other existing ERFE ELISAs (both R2 = 0.83). Nevertheless, employment of one optimal dilution of all serum samples is warranted to obtain reliable results. When adequately performed, the assay can be used to further unravel the human erythropoiesis-hepcidin-iron axis in various disorders and assess the added diagnostic value of ERFE.

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Section: Plos Onementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differentiating iron-loading anemias using a newly developed and analytically validated ELISA for human serum erythroferrone

et al. 2021

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“…Elevated urinary iron is common in SCD patients, especially during hemolytic crises, where iron levels are similar to those obtained via transfusions ( Porter and Garbowski, 2013 , Patel et al, 2023 ). Non-transfused patients often have abnormally low hepcidin levels, leading to increased iron absorption which can be exacerbated by suppressed ferroportin activity ( Girelli and Busti, 2020 , Mangaonkar et al, 2020 ). The intricate iron homeostasis in SCD is further complicated by the presence of substantial iron deposits in tissues that do not contribute to erythropoiesis and may not be reflected in serum ferritin levels ( Koduri, 2003 , Castro and Kato, 2015 ).…”

Section: Iron In Scdmentioning

confidence: 99%

“…Chronic overproduction of ERFE in mouse models caused systemic iron overload, increased plasma iron concentrations and hepatic tissue iron stores ( Coffey et al, 2022 ). Recent findings indicate ERFE's levels in SCD patients corresponds to the bone marrow's response to anemia, and might serve as a therapeutic target, particularly for those with iron overload ( Girelli and Busti, 2020 , Mangaonkar et al, 2020 ).…”

Section: Iron In Scdmentioning

confidence: 99%