title: A cytometric study of the red blood cells in Gaucher disease reveals their abnormal shape that may be involved in increased erythrophagocytosis.
abstract: BACKGROUND
  Gaucher disease is a sphingolipidosis caused by a deficiency of the enzyme glucocerebrosidase. Macrophages transform into pathogenic Gaucher cells following the phagocytosis of red blood cells (RBCs) and subsequent accumulation of glucosylceramide. Enhanced erythrophagocytosis is one feature of the disease indicating abnormal macrophage-RBC interactions. We hypothesized that the erythrophagocytosis observed in Gaucher disease may be at least partly due to abnormalities in the RBCs themselves.
  
  
  METHODS
  To investigate this hypothesis, we used flow cytometry FSC/SSC to study RBCs sampled from seven patients with Gaucher disease in terms of their shape and the expression of markers of senescence and phagocytosis. Cells from two of the seven patients were evaluated before and 9 months after the start of enzyme-replacement therapy.
  
  
  RESULTS
  Untreated patients were found to have abnormal flow-cytometry profiles suggesting an alteration of Gaucher RBC morphology. Scanning electron microscopy confirmed this finding by revealing many abnormally shaped RBCs. Whereas there was no evidence of desialylation of membrane glycoconjugates or phosphatidylserine exposure, RBC viability (calcein-AM test) and CD47 expression were reduced. These anomalies found in RBCs sampled from two patients before treatment, were no longer present after a 9 month-long enzyme-replacement therapy.
  
  
  CONCLUSIONS
  We report on previously overlooked alterations of Gaucher RBCs that may facilitate erythrophagocytosis in untreated patients. Their potential role in the anemia, the excess of aggregation and rheological anomalies associated with Gaucher disease must now be addressed. RBC anomalies may take part in the abnormal crosstalk between RBCs and macrophages leading to the accumulation of Gaucher cells.
authors.affiliation: National Institute for Biological Science Research and Development, Bucharest, Romania.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bratosin
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Tissier
authors.forename: Hélène
authors.initials: H
authors.lastname: Lapillonne
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Thierry Billette
authors.initials: TB
authors.lastname: de Villemeur
authors.forename: Coralia
authors.initials: C
authors.lastname: Cotoraci
authors.forename: Jean
authors.initials: J
authors.lastname: Montreuil
authors.forename: Cyril
authors.initials: C
authors.lastname: Mignot
mesh_terms: D000293:Adolescent; D001212:Asialoglycoproteins / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D051928:CD47 Antigen / Q000097:blood*; D002470:Cell Survival; D002648:Child; D002675:Child, Preschool; D057899:Cytophagocytosis; D056947:Enzyme Replacement Therapy; D004913:Erythrocytes, Abnormal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005776:Gaucher Disease / Q000097:blood* / Q000188:drug therapy; D005962:Glucosylceramidase / Q000627:therapeutic use; D006801:Humans; D008297:Male; D010718:Phosphatidylserines / Q000097:blood*
chemical_list: D001212:Asialoglycoproteins; D015415:Biomarkers; D051928:CD47 Antigen; D010718:Phosphatidylserines; D005962:Glucosylceramidase; C090568:imiglucerase