Evaluation of the main regulators of systemic iron homeostasis in pyruvate kinase deficiency
Abstract Iron homeostasis and dyserythropoiesis are poorly investigated in pyruvate kinase deficiency (PKD), the most common glycolytic defect of erythrocytes. Herein, we studied the main regulators of iron balance and erythropoiesis, as soluble transferrin receptor (sTfR), hepcidin, erythroferrone...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-31571-2 |
| _version_ | 1797864782434402304 |
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| author | Anna Zaninoni Roberta Marra Elisa Fermo Dario Consonni Immacolata Andolfo Anna Paola Marcello Barbara Eleni Rosato Cristina Vercellati Wilma Barcellini Achille Iolascon Paola Bianchi Roberta Russo |
| author_facet | Anna Zaninoni Roberta Marra Elisa Fermo Dario Consonni Immacolata Andolfo Anna Paola Marcello Barbara Eleni Rosato Cristina Vercellati Wilma Barcellini Achille Iolascon Paola Bianchi Roberta Russo |
| author_sort | Anna Zaninoni |
| collection | DOAJ |
| description | Abstract Iron homeostasis and dyserythropoiesis are poorly investigated in pyruvate kinase deficiency (PKD), the most common glycolytic defect of erythrocytes. Herein, we studied the main regulators of iron balance and erythropoiesis, as soluble transferrin receptor (sTfR), hepcidin, erythroferrone (ERFE), and erythropoietin (EPO), in a cohort of 41 PKD patients, compared with 42 affected by congenital dyserythropoietic anemia type II (CDAII) and 50 with hereditary spherocytosis (HS). PKD patients showed intermediate values of hepcidin and ERFE between CDAII and HS, and clear negative correlations between log-transformed hepcidin and log-EPO (Person’s r correlation coefficient = − 0.34), log-hepcidin and log-ERFE (r = − 0.47), and log-hepcidin and sTfR (r = − 0.44). sTfR was significantly higher in PKD; EPO levels were similar in PKD and CDAII, both higher than in HS. Finally, genotype–phenotype correlation in PKD showed that more severe patients, carrying non-missense/non-missense genotypes, had lower hepcidin and increased ERFE, EPO, and sTFR compared with the others (missense/missense and missense/non-missense), suggesting a higher rate of ineffective erythropoiesis. We herein investigated the main regulators of systemic iron homeostasis in the largest cohort of PKD patients described so far, opening new perspectives on the molecular basis and therapeutic approaches of this disease. |
| first_indexed | 2024-04-09T22:57:50Z |
| format | Article |
| id | doaj.art-e45c108bc3d24e5782f00ae3ca79ea19 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T22:57:50Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e45c108bc3d24e5782f00ae3ca79ea192023-03-22T11:10:38ZengNature PortfolioScientific Reports2045-23222023-03-011311710.1038/s41598-023-31571-2Evaluation of the main regulators of systemic iron homeostasis in pyruvate kinase deficiencyAnna Zaninoni0Roberta Marra1Elisa Fermo2Dario Consonni3Immacolata Andolfo4Anna Paola Marcello5Barbara Eleni Rosato6Cristina Vercellati7Wilma Barcellini8Achille Iolascon9Paola Bianchi10Roberta Russo11Hematology Unit, Pathophysiology of Anemias Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoDepartment of Molecular Medicine and Medical Biotechnology, University Federico IIHematology Unit, Pathophysiology of Anemias Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoEpidemiology Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoDepartment of Molecular Medicine and Medical Biotechnology, University Federico IIHematology Unit, Pathophysiology of Anemias Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoDepartment of Molecular Medicine and Medical Biotechnology, University Federico IIHematology Unit, Pathophysiology of Anemias Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoHematology Unit, Pathophysiology of Anemias Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoDepartment of Molecular Medicine and Medical Biotechnology, University Federico IIHematology Unit, Pathophysiology of Anemias Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoDepartment of Molecular Medicine and Medical Biotechnology, University Federico IIAbstract Iron homeostasis and dyserythropoiesis are poorly investigated in pyruvate kinase deficiency (PKD), the most common glycolytic defect of erythrocytes. Herein, we studied the main regulators of iron balance and erythropoiesis, as soluble transferrin receptor (sTfR), hepcidin, erythroferrone (ERFE), and erythropoietin (EPO), in a cohort of 41 PKD patients, compared with 42 affected by congenital dyserythropoietic anemia type II (CDAII) and 50 with hereditary spherocytosis (HS). PKD patients showed intermediate values of hepcidin and ERFE between CDAII and HS, and clear negative correlations between log-transformed hepcidin and log-EPO (Person’s r correlation coefficient = − 0.34), log-hepcidin and log-ERFE (r = − 0.47), and log-hepcidin and sTfR (r = − 0.44). sTfR was significantly higher in PKD; EPO levels were similar in PKD and CDAII, both higher than in HS. Finally, genotype–phenotype correlation in PKD showed that more severe patients, carrying non-missense/non-missense genotypes, had lower hepcidin and increased ERFE, EPO, and sTFR compared with the others (missense/missense and missense/non-missense), suggesting a higher rate of ineffective erythropoiesis. We herein investigated the main regulators of systemic iron homeostasis in the largest cohort of PKD patients described so far, opening new perspectives on the molecular basis and therapeutic approaches of this disease.https://doi.org/10.1038/s41598-023-31571-2 |
| spellingShingle | Anna Zaninoni Roberta Marra Elisa Fermo Dario Consonni Immacolata Andolfo Anna Paola Marcello Barbara Eleni Rosato Cristina Vercellati Wilma Barcellini Achille Iolascon Paola Bianchi Roberta Russo Evaluation of the main regulators of systemic iron homeostasis in pyruvate kinase deficiency Scientific Reports |
| title | Evaluation of the main regulators of systemic iron homeostasis in pyruvate kinase deficiency |
| title_full | Evaluation of the main regulators of systemic iron homeostasis in pyruvate kinase deficiency |
| title_fullStr | Evaluation of the main regulators of systemic iron homeostasis in pyruvate kinase deficiency |
| title_full_unstemmed | Evaluation of the main regulators of systemic iron homeostasis in pyruvate kinase deficiency |
| title_short | Evaluation of the main regulators of systemic iron homeostasis in pyruvate kinase deficiency |
| title_sort | evaluation of the main regulators of systemic iron homeostasis in pyruvate kinase deficiency |
| url | https://doi.org/10.1038/s41598-023-31571-2 |
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