vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v22i5.2645vsp-3303Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯORIGINAL ARTICLESОсобенности клеточного иммунитета у детей с врожденным ихтиозом и их роль в стратегии патогенетической терапии заболеванияFeatures of Cell-Mediated Immunity in Children with Congenital Ichthyosis and Their Role in the Pathogenetic Managementhttps://orcid.org/0000-0002-7335-6329АветисянК. О.AvetisyanKarine O.

Аветисян Карине Ониковна - младший научный сотрудник, врач аллерголог-иммунолог.

119296, Москва, Ломоносовский пр-т, д. 2, стр. 1, тел.: +7 (495) 967-14-20

Moscow

avetisyan.karine@mail.ruhttps://orcid.org/0000-0003-2252-8570МурашкинН. Н.MurashkinNikolay N.

Москва

Moscow

https://orcid.org/0000-0002-3056-403XМакароваС. Г.MakarovaSvetlana G.

Москва

Moscow

https://orcid.org/0000-0003-0896-6996ПетричукС. С.PetrichukSvetlana S.

Москва

Moscow

https://orcid.org/0000-0001-7771-3314КупцоваД. Г.KuptsovaDaria G.

Москва

Moscow

НМИЦ здоровья детейРоссияNational Medical Research Center of Children’s HealthRussian FederationНМИЦ здоровья детей; Первый МГМУ им. И.М. Сеченова (Сеченовский Университет); ЦГМАРоссияNational Medical Research Center of Children’s Health; Sechenov First Moscow State Medical University; Central State Medical Academy of Department of Presidential AffairsRussian FederationНМИЦ здоровья детей; РНИМУ им. Н.И. ПироговаРоссияNational Medical Research Center of Children’s Health; Pirogov Russian National Research Medical UniversityRussian Federation202305112023225415424Copyright © Аветисян К.О., Мурашкин Н.Н., Макарова С.Г., Петричук С.С., Купцова Д.Г., 20232023Аветисян К.О., Мурашкин Н.Н., Макарова С.Г., Петричук С.С., Купцова Д.Г.Avetisyan K.O., Murashkin N.N., Makarova S.G., Petrichuk S.S., Kuptsova D.G.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/3303Обоснование

Обоснование. Врожденные ихтиозы (ВИ) представляют собой гетерогенную клинико-этиологическую группу генодерматозов. Характерными клиническими симптомами заболевания, вне зависимости от форм, являются генерализованные эритродермия и шелушение, зуд, гиперкератоз, грубые структурные и функциональные нарушения эпидермального барьера, функций других органов и систем. Больные имеют чрезвычайно низкое качество жизни вследствие изменения внешнего вида, дискомфорта и постоянных симптомов заболевания. До настоящего времени не существует эффективных методов лечения ихтиоза, и научный поиск новых методов терапии является актуальной проблемой педиатрии и дерматологии детского возраста.

Цель исследования — изучение состояния клеточного иммунитета у больных с ВИ с помощью оценки субпопуляционного состава лимфоцитов в периферической крови. Было проведено исследование по изучению содержания основных и малых субпопуляций лимфоцитов у 86 пациентов с установленным диагнозом ВИ в возрасте от 1 мес до 18 лет. Диагноз был выставлен на основании клинических данных и результатов молекулярно-генетической диагностики. Проведен сравнительный анализ иммунологических показателей крови детей с ВИ и показателей пациентов с другими иммуноопосредованными хроническими дерматозами: атопическим дерматитом (АтД; n = 68) и вульгарным псориазом (n = 55).

Методы

Методы. Содержание Т-лимфоцитов, Т-хелперов (Th), цитотоксических Т-лимфоцитов (Tc), В-лимфоцитов, NK-клеток, регуляторных Т-клеток (Treg), активированных Т-хелперов (Thact), Th17-лимфоцитов в периферической крови изучено методом проточной цитометрии с использованием моноклональных антител. Статистический анализ проведен с использованием программы Statistica 10.0. Различия между группами оценены непараметрическим критерием Манна – Уитни, значимыми считали различия при p < 0,05.

Результаты

Результаты. Выявлено значимое повышенное содержание активированных T-хелперов в периферической крови у пациентов с ВИ и псориазом по сравнению с показателями детей с АтД (p < 0,001), а также повышенное содержание B-лимфоцитов и Treg в группе детей с ВИ (р < 0,05).

Заключение

Заключение. У детей с ВИ выявлены особенности клеточного иммунитета в виде патологической активации Th-лимфоцитов, нарушения терминальной дифференцировки наивных CD4+-клеток в сторону переключения на Thact, Treg, Th17-лимфоциты и их пролиферации. Сравнительный анализ вышеописанных иммунологических показателей у детей с ВИ, псориазом и АтД продемонстрировал сопоставимые результаты повышенного содержания Thact-лимфоцитов у больных в группах ВИ и псориаза. Полученные результаты открывают возможности применения иммунобиологических препаратов таргетной терапии псориаза в новой стратегии терапии детей с ВИ.

Background

Background. Congenital ichthyoses (CIs) are a heterogeneous clinical-etiological group of genodermatoses. Typical clinical symptoms of this disease, regardless of the form, are generalized erythroderma, peeling, itching, hyperkeratosis, severe structural and functional disorders of the epidermal barrier, other organs and systems. Patients have an extremely low quality of life due to changes in appearance, discomfort, constant disease symptoms. Thus far, there are no effective treatment methods for ichthyosis. That is why scientific search for new therapies is the topical issue in pediatrics and pediatric dermatology.

Objective

Objective. The aim of the study is to examine the cell-mediated immunity state in patients with CI via assessment of the pattern of lymphocyte subpopulations in peripheral blood. 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 (n = 55).

Methods

Methods. 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 at p < 0.05.

Results

Results. A significant increase of activated T-helpers level in peripheral blood was revealed in patients with CI and psoriasis compared to children with AD (p < 0.001), as well as an increased levels of B-lymphocytes and Treg in children with CI (p < 0.05).

Conclusion

Conclusion. Children with CI have shown some features of cell-mediated immunity such as: pathological activation of Th lymphocytes, impaired terminal differentiation of naive CD4+ cells to Thact, Treg, Th17 lymphocytes and their proliferation. Comparative analysis of mentioned immunological indicators in children with CI, psoriasis and AD has shown comparable results of increased Thact lymphocytes levels in patients in CI and psoriasis groups. This results open up potential of using immunobiological drugs of psoriasis target therapy within the new management strategy for children with CI.

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The authors declare that there are no conflicts of interest present.