Down-regulation of Regulatory T-cells in Children With Gaucher Disease Under Enzyme Replacement Therapy.

ABSTRACT

Gaucher disease (GD) is one of the most important lysosomal storage disorders. T-lymphocytes perform and regulate many of the immune processes and play a major role in immune homeostasis. Studies have shown that GD causes impairment in T-lymphocyte functions, although the role and status of T-lymphocytes in GD are still under investigation. It is still not fully known how GD leads to the altered biochemical and immunological cellular functions observed in the disease. Our study aimed to evaluate the variations of regulatory T-lymphocytes (Tregs) in 20 Egyptian children with GD under enzyme replacement therapy, managed in Assiut University Hospitals. Tregs were detected using 3-color flow cytometric immunophenotyping, in which subpopulations of T-lymphocytes and the expression of CD4+ on their surfaces were gated. The expression of CD25+ was assessed on CD4+ cells with different gates to define CD4+CD25, CD4+CD25+high, and CD4+CD25+ low cells. Then, CD4+CD25+highFoxp3+cells and MFI of Foxp3+ expression on CD4+CD25+ high were determined. We found the levels of CD4+CD25+/CD4+, CD4+CD25+high/CD4+, CD4+CD25+highFoxp3+ Tregs, and median fluorescence intensity of Foxp3+ expression on CD4+CD25+high were significantly lower in children with GD compared to healthy controls. In conclusion, our data showed significantly decreased regulatory T-lymphocytes in children with GD. The reduced effect of Tregs may have a role in the pathogenesis of immune dysregulation in children with GD. The relationship of these cells to immune disorders in GD children remains to be determined. Therefore, we recommend further studies to elucidate the role and function of Tregs in GD and its potential role in the disease phenotype, as well as how it is affected by electrical resistivity tomography.