Leukocyte perturbation associated with Fabry disease

ROZENFELD PA; AGRIELLO E; DE FRANCESCO, PN; MARTINEZ P; FOSSATI CA

JOURNAL OF INHERITED METABOLIC DISEASE

Springer

Lugar: Heidelberg; Año: 2009 p. 1 - 11

0141-8955

Fabry disease is an X-linked lysosomal storage disorder of glycosphingolipids catabolism, due to the deficient activity of the enzyme alpha-galactosidase A. The non-degraded substrate, mainly globotriaosylceramide (Gala1-4Galb1-4Glcb1-1Cer; Gb3) accumulates progressively in the lysosome of different cells. The aim of this work is to analyze changes in leukocyte subpopulations and surface markers and to determine whether Gb3 is increased in leukocytes of patients with untreated and treated Fabry disease. Blood samples obtained from 22 Fabry male patients (11 untreated and 11 on enzyme replacement therapy) and 22 normal controls were subjected to flow cytometic analysis of Gb3 intracellular content, leukocyte subpopulations and cell markers. Based on the fluorescence intensity of bound monoclonal antibody, and relative to normal control leukocytes, GB3 appeared significantly increased in lymphocytes (but not in monocytes or granulocytes) from patients with Fabry disease. A significantly higher percentage of lymphocytes and CD19+ cells and a reduced proportion of monocytes, CD8+ cells, and myeloid dendritic cells were detected in Fabry patients´ samples as compared to normal controls. CD1d expression was significantly lower and MHC class II surface expression was significantly higher in monocytes from Fabry patients as compared to normal controls. As previously observed for other adhesion molecules, the expression of CD31 (PECAM) was higher in leucocytes from Fabry patients. In conclusion, the differences recorded in this study reveal a leukocyte perturbation associated to the disease state in Fabry patients, whereas some abnormalities are less marked in treated patients.