FEATURES OF LYMPHOCYTE SUBPOPULATIONS IN PATIENTS WITH DIFFERENT FORMS OF HYPER IGE SYNDROME

Abstract

Introduction. Patients with hyper IgE syndrome are characterized by eosinophilia, low levels of inflammatory markers, severe destructive pneumonia, chronic mucosal candidiasis, severe atopic dermatitis, skeletal lesions: osteopenia and pathological fractures, scoliosis, late change of primary teeth. The pathogenesis of this syndrome is based on defects in signal transduction from cytokine receptors, caused by mutations in the STAT3 gene (autosomal dominant form), ZNF341, DOCK8, PGM3 and CARD11 (autosomal recessive form) and in genes encoding cytokine receptor subunits (IL6ST, etc.). The aim of the study was to analyze lymphocyte subpopulations in patients with different forms of hyper IgE syndrome. Materials and methods. The study included 9 patients with hyper IgE syndrome. Lymphocyte subpopulations were assessed by flow cytometry, total IgE - immunoturbidimetry, DNA sequencing - NGS. Results. Mutations in different exons of the STAT3 gene and in the IL6ST gene were detected in patients. No statistically significant differences were found between the subpopulations of CD3 T lymphocytes: CD4 T helpers naive and memory, CD8 T cytotoxic naive and memory, early thymic emigrants, T regulatory cells, T helpers types 1 and 2 compared to the control group (p> 0.05). However, the subpopulation of T helpers 17 was significantly reduced, both in relative (p<0.001) and absolute number (p=0.003) only in patients with mutations in the STAT3 gene. In patients with hyper IgE syndrome, both the relative (p<0.001) and absolute numbers of unswitched (p=0.001) and switched memory B cells (p=0.007) were reduced. A decrease in the relative number of plasmablasts (p=0.022) and activated B lymphocytes (p=0.001) was also observed. Conclusions. The number of T-helpers 17 depended on the type of hyper IgE syndrome. Memory B cells were reduced in all mutation types. The method of assessing T helper 17 demonstrated its diagnostic efficiency. We observed differences in the clinical picture and severity of the disease depending on the STAT3 protein domain mutation. However, further studies with a larger number of patients are needed.