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.

Age-related changes in the parameters of cellular immunity, the activity of intracellular lymphocyte dehydrogenases and functional activity of neutrophils in children with Gaucher disease

“…В нашем исследовании оценка содержания регуляторных Т-лимфоцитов у детей с БГ выявила снижение доли только во 2-й и 4-й возрастных группах, в остальных группах содержание клеток соответствовало референсным значениям. Похожий результат был описан A.M. Zahran о снижении данной популяции при анализе ограниченной выборки у 20 пациентов с БГ [12].…”

“…в сторону провоспалительных цитокинов и развитие хронического воспаления с вовлечением всех иммунных клеток, что может приводить к изменению состава как основных, так и малых популяций лимфоцитов [12]. Так, на выборке из 20 пациентов с БГ показано увеличение доли цитотоксических Т-клеток и снижение NK-клеток по сравнению со здоровыми людьми, данный факт авторы связывают с участием данных популяций в патогенезе и прогрессировании БГ [13].…”

“…Помимо этого, показано, что, несмотря на ФЗТ, Т-хелперы и B-регуляторные клетки у пациентов с БГ значительно снижены по сравнению с контрольной группой [14]. Показано также значительное снижение доли регуляторных Т-лимфоцитов и их функциональной активности у детей с БГ [12].…”

C-X-C Motif Chemokine Ligand 9 and Its CXCR3 Receptor Are the Salt and Pepper for T Cells Trafficking in a Mouse Model of Gaucher Disease

“…CD8 + T cells are important for inducing autoimmune and the anti-cancer and anti-viral responses [ 37 , 38 , 39 , 40 ]. T cell defects, T cell lymphomas, and increased incidence of CD3 + , CD4 + , CD8 + , CD3 + HLA-DR + , CD4 + HLA-DR + , and CD8 + HLA-DR + subset of activated T cells have been observed in lung and peripheral blood of patients with GD [ 41 , 42 , 43 , 44 , 45 , 46 ]. Significantly elevated levels of CD4 + T cells and modest changes in CD8 + T cells were present in liver, lung, spleen, and thymus of Gba1 9V/− mice [ 5 , 6 , 47 ].…”