title: Unexpected macrophage-independent dyserythropoiesis in Gaucher disease.
abstract: Gaucher disease is a rare inherited disease caused by a deficiency in glucocerebrosidase leading to lipid accumulation in cells of mononuclear-macrophage lineage known as Gaucher cells. Visceral enlargement, bone involvement, mild anemia and thrombocytopenia are the major manifestations of Gaucher disease. We have previously demonstrated that the red blood cells from patients exhibit abnormal properties, which indicates a new role in Gaucher disease pathophysiology. To investigate whether erythroid progenitors are affected, we examined the in vitro erythropoiesis from the peripheral CD34+cells of patients and controls. CD34- cells were differentiated into macrophages and co-cultivated with erythroblasts. We showed an accelerated differentiation of erythroid progenitors without maturation arrest from patients compared to controls. This abnormal differentiation persisted in the patients when the same experiments were performed without macrophages, which strongly suggested that dyserythropoiesis in Gaucher disease is secondary to an inherent defect in the erythroid progenitors. The accelerated differentiation was associated with reduced cell proliferation. As a result, less mature erythroid cells were generated in vitro in the Gaucher disease cultures compared to the control. We then compared the biological characteristics of untreated patients according to their anemic status. Compared to the non-anemic group, the anemic patients exhibit higher plasma levels of growth differentiation factor-15, a marker of ineffective erythropoiesis, but they had no indicators of hemolysis and similar reticulocyte counts. Taken together, these results demonstrated an unsuspected dyserythropoiesis that was independent of the macrophages and could participate, at least in part, to the basis of anemia in Gaucher disease.
authors.affiliation: Université Sorbonne Paris Cité, Université Paris Diderot, Inserm, INTS, Unité Biologie Intégrée du Globule Rouge, Laboratoire d'Excellence GR-Ex, Paris.
authors.forename: Nelly
authors.initials: N
authors.lastname: Reihani
authors.affiliation: Sorbonne Paris-Cité, Université Paris Descartes, Service de Médecine Interne, Assistance publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Inserm UMR 1163, CNRS ERL 8254, Hôpital Necker, Institut Imagine, Laboratoire d'excellence GR-Ex, Paris.
authors.forename: Jean-Benoit
authors.initials: JB
authors.lastname: Arlet
authors.affiliation: Sorbonne Paris-Cité, Université Paris Descartes, Inserm UMR 1163, CNRS ERL 8254, Institut Imagine, Hôpital Necker, Laboratoire d'excellence GR-Ex, Paris.
authors.forename: Michael
authors.initials: M
authors.lastname: Dussiot
authors.affiliation: Sorbonne Université, Université Pierre et Marie Curie, Service de Neuropédiatrie Hôpital Trousseau, Assistance publique-Hôpitaux de Paris, Hôpital et GRC ConCer-LD, Paris.
authors.forename: Thierry Billette
authors.initials: TB
authors.lastname: de Villemeur
authors.affiliation: Hôpitaux universitaires Paris Nord Val de Seine, Assistance publique-Hôpitaux de Paris, Hôpital Beaujon, Service de Médecine Interne, Centre de Référence des Maladies Lysosomales, Clichy, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Belmatoug
authors.affiliation: Université Catholique de Lille, Hôpital Saint Vincent de Paul, Service d'Hématologie, Lille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Rose
authors.affiliation: Université Sorbonne Paris Cité, Université Paris Diderot, Inserm, INTS, Unité Biologie Intégrée du Globule Rouge, Laboratoire d'Excellence GR-Ex, Paris.
authors.forename: Yves
authors.initials: Y
authors.lastname: Colin-Aronovicz
authors.affiliation: Sorbonne Paris-Cité, Université Paris Descartes, Assistance publique-Hôpitaux de Paris, Hôpital Necker, Service d'Hématologie, Inserm UMR 1163, CNRS ERL 8254, Institut Imagine, Laboratoire d'excellence GR-Ex, Paris, Inserm UMR 1163, CNRS, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Université Sorbonne Paris Cité, Université Paris Diderot, Inserm, INTS, Unité Biologie Intégrée du Globule Rouge, Laboratoire d'Excellence GR-Ex, Paris.
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Van Kim
authors.affiliation: Université Sorbonne Paris Cité, Université Paris Diderot, Inserm, INTS, Unité Biologie Intégrée du Globule Rouge, Laboratoire d'Excellence GR-Ex, Paris melanie.franco@inserm.fr.
authors.forename: Melanie
authors.initials: M
authors.lastname: Franco
mesh_terms: D000740:Anemia / Q000209:etiology; D015415:Biomarkers; D002454:Cell Differentiation; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D003114:Colony-Forming Units Assay; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism; D004909:Erythrocyte Indices; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis; D005260:Female; D005776:Gaucher Disease / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D016130:Immunophenotyping; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010641:Phenotype
chemical_list: D015415:Biomarkers