Features of lymphocyte subpopulations in patients with different forms of hyper-IgE syndrome

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, delayed 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 our study was to analyze lymphocyte subpopulations in patients with different forms of hyper-IgE syndrome. The study included 9 patients with hyper-IgE syndrome. Lymphocyte subpopulations were assessed by flow cytometry; total IgE, by immunoturbidimetry; DNA sequencing, by means of NGS methodology. Mutations in different exons of the STAT3 gene and in the IL6ST gene were detected in patients. No statistically significant differences were found between patients and control group of CD3 T cell subpopulations, i.e., CD4 T helpers (naive and memory cells), CD8 T cytotoxic (naive and memory cells), early thymic emigrants, Treg cells, T helpers (type 1 and 2) (p 0.05). However, the subpopulation of T helpers 17 was significantly reduced, both in relative (p 0.001) and absolute numbers (p = 0.003) only in patients with mutations in the STAT3 gene. In patients with hyper-IgE syndrome, we have found a reduction of both relative (p 0.001) and absolute numbers of unswitched (p = 0.001) and switched memory B cells (p = 0.007). A decreased relative number of plasmablasts (p = 0.022) and activated B lymphocytes (p = 0.001) was also observed. 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. The differences were observed in clinical pattern and severity of the disease depending on the STAT3 protein domain mutation. However, further studies with a larger number of patients are required.