medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-498medsovet-8101Research ArticleАЛЛЕРГОЛОГИЯ И ИММУНОЛОГИЯALLERGOLOGY AND IMMUNOLOGYКлинико-иммунологические проявления полиморфизмов генов цитокинов при контролируемой и неконтролируемой бронхиальной астме у детейClinical and immunological manifestations of gene polymorphisms cytokines in controlled and uncontrolled bronchial asthmahttps://orcid.org/0000-0002-1089-8884СупрунЕ. Н.SuprunE. N.

Супрун Евгений Николаевич, к.м.н., врач аллерголог-иммунолог; старший научный сотрудник группы медико-экологических проблем здоровья матери и ребенка лаборатории комплексных методов исследования бронхолегочной и перинатальной патологии; доцент кафедры госпитальной и факультетской педиатрии с курсом пропедевтики детских болезней

680022, Хабаровск, ул. Воронежская, д. 49, корп. 1

680000, Хабаровск, ул. Муравьева- Амурского, д. 35

Evgeniy N. Suprun, Cand. Sci. (Med.), Allergist-Immunologist; Senior Researcher of Groups of Health and Environmental Problems of Mother and Child Health of Laboratory of Integral Methods of Bronchopulmonary and Perinatal Pathology Research; Associate Professor of the Department of Hospital and Faculty Pediatrics with a Course of Propaedeutics of Children’s Diseases

49, Bldg. 1, Voronezhskaya St., Khabarovsk, 680022

35, Muravyov- Amursky St., Khabarovsk, 680000

 

evg-suprurn@yandex.ruhttps://orcid.org/0000-0001-6724-3654СупрунС. В.SuprunS. V.

Супрун Стефания Викторовна, д.м.н., главный научный сотрудник группы медико-экологических проблем здоровья матери и ребенка лаборатории комплексных методов исследования бронхолегочной и перинатальной патологии

680022, Хабаровск, ул. Воронежская, д. 49, корп. 1

Stefaniya V. Suprun, Dr. Sci. (Med.), Main Staff Scientist of Groups of Health and Environmental Problems of Mother and Child Health of Laboratory of Integral Methods of Bronchopulmonary and Perinatal Pathology Research

49, Bldg. 1, Voronezhskaya St., Khabarovsk, 680022

   

stefanya-suprun@yandex.ruhttps://orcid.org/0000-0002-0255-3202НаговицинаЕ. Б.NagovitsinaE. B. 

Наговицына Елена Борисовна, к.м.н., старший научный сотрудник группы молекулярно-генетической диагностики лаборатории комплексных методов исследования бронхолегочной и перинатальной патологии

680022, Хабаровск, ул. Воронежская, д. 49, корп. 1

Elena B. Nagovitsina, Cand. Sci. (Med.), Senior Researcher, Molecular Genetic Diagnosis Group of Laboratory of Integral Methods of Bronchopulmonary and Perinatal Pathology Research

49, Bldg. 1, Voronezhskaya St., Khabarovsk, 680022

   

nebo59@yandex.ruhttps://orcid.org/0000-0002-0099-7459ГалянтО. И.GalyantO. I.

Галянт Оксана Игоревна, к.м.н., старший научный сотрудник группы клинической иммунологии и эндокринологии лаборатории комплексных методов исследования бронхолегочной и перинатальной патологии

680022, Хабаровск, ул. Воронежская, д. 49, корп. 1

Oxana I. Galyant, Cand. Sci. (Med.), Senior Researcher of the Group of Clinical Immunology and Endocrinology of Laboratory of Integral Methods of Bronchopulmonary and Perinatal Pathology Research

49, Bldg. 1, Voronezhskaya St., Khabarovsk, 680022

   

galyant80@mail.ruhttps://orcid.org/0000-0002-8855-7422ЛебедькоО. А.Lebed’koO. A.

Лебедько Ольга Антоновна, д.м.н., заведующая лабораторией комплексных методов исследования бронхолегочной и перинатальной патологии, директор

680022, Хабаровск, ул. Воронежская, д. 49, корп. 1

Olga A. Lebed’ko, Dr. Sci. (Med.), Senior Researcher Laboratory of Integral Methods of Bronchopulmonary and Perinatal Pathology Research, Director

49, Bldg. 1, Voronezhskaya St., Khabarovsk, 680022

   

leoaf@mail.ruХабаровский филиал Дальневосточного научного центра физиологии и патологии дыхания – Научно-исследовательский институт охраны материнства и детства; Дальневосточный государственный медицинский университетРоссияKhabarovsk Branch of Far Eastern Scientific Center of Physiology and Pathology of Respiration Research Institute of Maternity and Childhood Protection; Far-Eastern State Medical UniversityRussian FederationХабаровский филиал Дальневосточного научного центра физиологии и патологии дыхания – Научно-исследовательский институт охраны материнства и детстваРоссияKhabarovsk Branch of Far Eastern Scientific Center of Physiology and Pathology of Respiration Research Institute of Maternity and Childhood ProtectionRussian Federation20242702202401228–239Copyright © Супрун Е.Н., Супрун С.В., Наговицина Е.Б., Галянт О.И., Лебедько О.А., 20242024Супрун Е.Н., Супрун С.В., Наговицина Е.Б., Галянт О.И., Лебедько О.А.Suprun E.N., Suprun S.V., Nagovitsina E.B., Galyant O.I., Lebed’ko O.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/8101Введение

Введение. Бронхиальная астма (БА) – многофакторное заболевание, но в основе его патогенеза у детей лежит атопическое воспаление, на борьбу с которым и направлены современные средства терапии, меньшее внимание уделяется факторам неспецифического воспаления, которые тоже могут влиять на контролируемость патологического процесса. Регуляцию любого воспаления осуществляют в первую очередь цитокины, поэтому именно изучению полиморфизмов генов цитокинов неспецифического воспаления посвящена данная работа.

Цель

Цель. Выявить ассоциацию полиморфизмов генов цитокинов с клинико-иммунологическими особенностями неконтролируемого течения бронхиальной астмы.

Материалы и методы

Материалы и методы. Обследовано 167 детей с бронхиальной астмой, которые разделены на группы с полным контролем заболевания и без него согласно стандарту клинических рекомендаций по бронхиальной астме. Дополнительно определялись мононуклеотидные замены в генах цитокинов: IL4-C589T (rs2243250), IL6-C174G (rs1800795), IL10-G1082A (rs1800896), IlL10-C592A (rs1800872), IL10-C819T (rs1800871), IL12B-A1188C (rs3212227), TNFα- G308A (rs1800629), уровень цитокинов в сыворотке крови: IL4, 5, 6, 7, 8, 9, 10, 18 и TNFα; стандартные показатели иммунограммы: субпопуляции лимфоцитов, нейтрофильного фагоцитоза и уровень Ig A, M, G, E.

Результаты и обсуждение

Результаты и обсуждение. Определено, что каждая из клинически значимых мононуклеотидных замен формирует уникальный цитокиновый и иммунный профиль, фенотипически реализующийся в клинических проявлениях заболевания. Доказано, что мононуклеотидные замены IL10-C592A, TNFα- G308A способствуют лучшему контролю с тенденцией к более легкому течению бронхиальной астмы; дети с полиморфизмом IL6-C174G переносят заболевание тяжелее с тенденцией к снижению контроля. Кроме того, мононуклеотидные замены в генах сигнальных молекул иммунной системы модифицируют атопическое воспаление, ослабляя (IL10-C592A, TNFα- G308A) или усиливая (IL6-C174G) его, что приводит к изменению (уменьшению либо увеличению) дозы топических глюкокортикостероидов соответственно.

Выводы

Выводы. Таким образом, определение полиморфизмов IL6-C174G (rs1800795), IL10-C592A (rs1800872), TNFα- G308A (rs1800629) у детей с бронхиальной астмой помогает выявлять группу риска по тяжелому и неконтролируемому течению заболевания, а также персонифицировать терапию.

Introduction

Introduction. Bronchial asthma (BA) is a multifactorial disease, but its pathogenesis in children is based on atopic inflammation, which is what modern therapies are aimed at combating; less attention is paid to factors of nonspecific inflammation, but they also affect the controllability of the pathological process. The regulation of any inflammation is carried out primarily by cytokines, therefore this work is devoted to the study of polymorphisms of genes for cytokines of nonspecific inflammation.

Aim

Aim. To explore the association between cytokine gene polymorphisms and clinical immunological features of uncontrolled asthma.

Materials and methods

Materials and methods. We examined 167 children with asthma, who were divided into groups with and without complete disease control, according to the standard of clinical guidelines for asthma. Additionally, mononucleotide substitutions in the cytokine genes were determined: IL4-C589T (rs2243250), IL6-C174G (rs1800795), IL10-G1082A (rs1800896), IlL10-C592A (rs1800872), IL10- C819T (rs1800871), IL12B-A118 8C (rs3212227) , TNFα- G308A (rs1800629), serum cytokine levels: IL4, 5, 6, 7, 8, 9, 10, 18 and TNFα; standard immunogram indicators: subpopulations of lymphocytes, neutrophil phagocytosis and levels of Ig A, M, G, E.

Results and discussion

Results and discussion. It was determined that each of the clinically significant mononucleotide substitutions forms a unique cytokine and immune profile that is phenotypically realized in the clinical manifestations of the disease. It has been proven that mononucleotide substitutions IL10-C592A, TNFα- G308A contribute to better control with a tendency to milder asthma; children with the IL6-C174G polymorphism experience more severe disease with a tendency toward decreased control. In addition, mononucleotide substitutions in the genes of signaling molecules of the immune system modify atopic inflammation, weakening (IL10-C592A, TNFα- G308A) or enhancing (IL6-C174G) it, which leads to a change (decrease or increase) in the dose of TGCS, respectively.

Conclusion

Conclusion. Thus, determination of IL6-C174G (rs1800795), IL10-C592A (rs1800872), TNFα- G308A (rs1800629) polymorphisms in children with ВА helps to identify a risk group for severe and uncontrolled disease, as well as to personalize therapy. 

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