1. Enzyme replacement therapy improves erythropoiesis and iron dysregulation in Gaucher disease.
- Author
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Motta I, Delbini P, Scaramellini N, Ghiandai V, Duca L, Nava I, Nascimbeni F, Lugari S, Consonni D, Trombetta E, Di Stefano V, Migone De Amicis M, Cassinerio E, Carubbi F, and Cappellini MD
- Subjects
- Humans, Male, Female, Adult, Adolescent, Child, Middle Aged, Child, Preschool, Young Adult, Follow-Up Studies, Glucosylceramidase therapeutic use, Anemia drug therapy, Anemia etiology, Ferritins blood, Hyperferritinemia etiology, Hyperferritinemia drug therapy, Gaucher Disease drug therapy, Gaucher Disease blood, Enzyme Replacement Therapy, Erythropoiesis drug effects, Iron metabolism
- Abstract
Anemia and hyperferritinemia are frequent findings at diagnosis of Gaucher disease (GD). Macrophage-independent dyserythropoiesis and abnormal iron metabolism have been shown. We evaluated hematological and iron status at diagnosis (T0) and the effect of enzyme replacement therapy (ERT) on erythropoiesis and iron utilization over 5-year follow-up in type 1 GD patients and in an ex vivo model of erythropoiesis from CD34 + peripheral blood cells. At T0, 41% of patients had anemia and 51% hyperferritinemia. Hemoglobin increased from 12.6 (T0) to 13.9 g/dL (T6), GFD15, a marker of ineffective erythropoiesis, decreased from 5401 to 710 pg/ml, and serum ferritin decreased from 614 to 140 mcg/L (p < 0.001). In parallel, transferrin saturation (TSAT) increased. Hepcidin, although in the normal range, decreased from T0 to T6. Ex vivo studies showed that ERT restores the erythroid cells derived from CD34 + impaired ability to differentiate. During ERT, an increase in TFRC expression, consistent with the ability of erythroid precursors to uptake iron, and a reduction in HAMP and concomitant increase in SLC40A1 were observed. This is the largest study with a longitudinal follow-up evaluating erythropoiesis and iron metabolism, combining clinical and ex vivo data in GD. Iron dysregulation likely contributes to anemia, and ERT, by improving iron distribution, improves erythropoiesis., Competing Interests: Declarations. Ethics approval: The study was approved by the ethical review committee of the center “Comitato Etico Milano Area 2” (Protocol number 1678/2016) and was carried out in compliance with the principles established in the Helsinki Declaration. Competing interests: Irene Motta has been or is a current consultant for Sanofi, Bristol Myers Squibb, and Amicus Therapeutics and has received honoraria for lectures, financial support, and grants from Sanofi.Fabio Nascimbeni has been or is a current consultant for Sanofi.Francesca Carubbi received financial support and grants from Sanofi, Amgen.Maria Domenica Cappellini has been or is a current consultant for Sanofi, Novartis, Celgene Corp (Bristol Myers Squibb), Vifor Pharma and Ionis Pharmaceuticals, and received research funding from Sanofi, Novartis, Celgene Corp (Bristol Myers Squibb), La Jolla Pharmaceutical Company, Roche, Protagonist Therapeutics, and CRISPR Therapeutics., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2024
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