Activity of the nuclear transcription factor NF-κB in lymphocyte populations in children with Gaucher disease

The study is devoted to the role of the transcription factor NF-κB in pathogenesis of chronic inflammation in Gaucher disease (GD) in children. Gaucher disease is an orphan autosomal recessive lysosomal disorder characterized by mutations in the β-glucocerebrosidase gene, leading to a decrease in the activity of this enzyme and, as a consequence, to the accumulation of the substrate – glucoceramide. Macrophages transformed to Gaucher cells, due to the accumulation of glucoceramide, secrete proinflammatory cytokines (IL-1β, IL-6, TNFα), triggering chronic inflammation in internal organs via activation of NF-κB nuclear transcription factor along the canonical pathway. The aim of the work was to assess the proportion of cells with the activity of the nuclear transcription factor NF-κB in lymphocyte populations in children with GD. The ratio of cells with NF-κB translocation in peripheral blood lymphocyte populations was assessed in 70 GD patients (type 1, 58 cases; type 3, 12 patients) receiving enzyme replacement therapy, and in 30 conditionally healthy children. The results of the studies revealed a significantly increased proportion of cells with NF-κB translocation in T lymphocytes, T helpers, cytotoxic T cells, NK cells, B lymphocytes, as well as in T helpers type 17, activated T helpers and in regulatory T cells in GD patients compared with control group (p 0.001). In children with GD, the highest number of cells with NF-κB translocation was found in B lymphocytes and NK cell populations. In the course of the study of patients with different types of GD, it was found that in children with type 1 GD, a significant increase in the level of NF-κB translocation was observed in all studied lymphocyte populations. In patients with type 3 GD, a significant increase in NF-κB translocation in T lymphocytes, T helpers, cytotoxic T lymphocytes, NK cells, Th17 cells, activated T helpers and regulatory T cells was also noted, relative to the comparison group. However, in the populations of B lymphocytes and double negative T lymphocytes in patients with type 3 GD, no statistically significant differences were found against the comparison group. The results of the study confirm the key role of NF-κB in maintaining chronic inflammation in Gaucher disease. Modern flow cytometry approach with visualization allows to determine NF-κB activity in different populations of peripheral blood lymphocytes, including Th17 and Treg, with high accuracy. It is advisable to conduct additional studies concerning the effect of initiated enzyme replacement therapy on NF-κB activity in lymphocyte populations of children with Gaucher disease.