A New Treatment Strategy For Children With Congenital Ichthyosis Based on Immunopathogenesis

Abstract

Congenital ichthyosis (CI) is a clinico-genetic heterogeneous disease and belongs to the group of severe genodermatoses. Characteristic clinical symptoms of the disease are erythroderma and peeling, itching, hyperkeratosis, gross structural and functional disorders of the epidermal barrier, functions of other organs and systems. Patients have an extremely low quality of life due to changes in appearance, discomfort and persistent symptoms of the disease. There are no effective methods of treating ichthyosis now. Scientists all over the world are developing new methods of treatment. Our research group set a task to find new methods of treating children with CI. We carried out scientific work to study immunopathogenetic mechanisms in patients with CI. The aim of the study was to examine the cell-mediated immunity state in patients with CI via assessment of the pattern of lymphocyte subpopulations in peripheral blood. Methods:The research was conducted to study the content of the main and small lymphocyte subpopulations in 86 patients with established diagnosis of CI aged from 1 month to 18 years. The diagnosis was made according to the clinical data and the results of molecular genetic testing. Comparative analysis of blood immunological indicators in children with CI and in patients with other immunemediated chronic dermatoses: atopic dermatitis (AD; n = 68) and psoriasis vulgaris (Ps; n = 55). The level of T lymphocytes,T helpers (Th), cytotoxic T lymphocytes (Tc), B lymphocytes, NK cells, Treg-cells (Treg), activated T helpers (Thact), Th17 lymphocytes in peripheral blood was evaluated via flow cytometry using monoclonal antibodies. Statistical analysis was performed via Statistica 10.0. Differences between the groups were assessed via Mann-Whitney non-parametric test, differences were considered significant atp < 0.05. Results: A significant increase in the content of activated T-helpers in peripheral blood was revealed in patients with CI and Ps compared with those of children with AD (p < 0.001). And also in children with CI, there was an increased content of B-lymphocytes, Treg- and T17- lymphocytes. The obtained results opened up the possibility for us to use drugs for immunobiological targeted therapy of Ps in a new treatment strategy for children with CI. We performed targeted immunosuppressive therapy in children from the CI group who had increased activation and proliferation of CD4+ lymphocytes. In a short time after initiation of therapy, there was a significant decrease in erythroderma and itching, and an improvement in the quality of life of patients and their families. Conclusion: Immunological dysregulation in children with CI is presented in the form of pathological activation of Th-lymphocytes, as a result of terminal differentiation of naive CD4+ cells towards switching to Thact, Treg, Th17- lymphocytes. A comparative analysis of immunological parameters in children with CI, Ps and AD demonstrated comparable results of Thact immunophenotypes in patients in CI and Ps groups. A new strategy in therapy in children with CI based on immunopathogenesis has demonstrated its therapeutic effectiveness in real clinical practice