Leukocyte perturbation associated with Fabry disease

Area of Science:

• Biochemistry
• Immunology
• Genetics

Background:

• Fabry disease is an X-linked lysosomal storage disorder caused by deficient alpha-galactosidase A activity.
• This deficiency leads to the accumulation of globotriaosylceramide (Gb(3)) in various cells.
• Leukocyte alterations in Fabry disease are not fully understood.

Purpose of the Study:

• To analyze changes in leukocyte subpopulations and surface markers in Fabry disease patients.
• To determine if globotriaosylceramide (Gb(3)) is elevated in leukocytes of untreated and treated Fabry patients.
• To investigate the impact of enzyme replacement therapy on leukocyte profiles.

Main Methods:

• Flow cytometry was used to analyze Gb(3) intracellular content, leukocyte subpopulations, and cell markers.
• Blood samples from 22 male Fabry patients (11 untreated, 11 treated) and 22 controls were analyzed.
• Specific markers included CD19, CD8, myeloid dendritic cells, CD1d, MHC class II, and CD31 (PECAM).

Main Results:

• Globotriaosylceramide (Gb(3)) was significantly increased in lymphocytes, but not monocytes or granulocytes, of Fabry patients.
• Fabry patients showed a higher percentage of lymphocytes and CD19(+) cells, with reduced monocytes, CD8(+) cells, and myeloid dendritic cells.
• Monocytes displayed lower CD1d expression and higher MHC class II expression; CD31 (PECAM) was elevated on leukocytes.

Conclusions:

• Fabry disease is associated with significant leukocyte perturbations, including Gb(3) accumulation in lymphocytes.
• Specific changes in lymphocyte and monocyte populations and marker expression are characteristic of the disease.
• Enzyme replacement therapy may mitigate some of these leukocyte abnormalities.