ABSTRACT
Fabry disease is an X-linked lysosomal storage disorder of glycosphingolipid catabolism due to the deficient activity of the enzyme alpha-galactosidase A. The non-degraded substrate, mainly globotriaosylceramide (Galα1-4Galß1-4Glcß1-1Cer; Gb(3)) accumulates progressively in the lysosome of various cells. The aim of this work was to analyse changes in leukocyte subpopulations and surface markers and to determine whether Gb(3) is increased in leukocytes of patients with untreated and treated Fabry disease. Blood samples obtained from 22 male Fabry patients (11 untreated and 11 on enzyme replacement therapy) and 22 normal controls were subjected to flow cytometric analysis of Gb(3) intracellular content, leukocyte subpopulations and cell markers. Based on the fluorescence intensity of bound monoclonal antibody, and relative to normal control leukocytes, Gb(3) 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 samples from Fabry patients compared with normal controls. CD1d expression was significantly lower and MHC class II surface expression was significantly higher in monocytes from Fabry patients than in normal controls. As previously observed for other adhesion molecules, the expression of CD31 (PECAM) was higher in leukocytes from Fabry patients. In conclusion, the differences recorded in this study reveal a leukocyte perturbation associated with the disease state in Fabry patients, whereas some abnormalities are less marked in treated patients.
