medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2025-034medsovet-9188Research ArticleХРОНИЧЕСКИЕ ЗАБОЛЕВАНИЯ ЛЕГКИХCHRONIC PULMONARY DISEASESПрогностические молекулярные маркеры эффективности биологической терапии тяжелой бронхиальной астмыPrognostic molecular markers of the biological therapy effectiveness for severe bronchial asthmahttps://orcid.org/0000-0003-4678-3904ТитоваО. Н.TitovaO. N.

Титова Ольга Николаевна, д.м.н., профессор, директор

197022, Санкт-Петербург, ул. Льва Толстого, д. 6–8

Olga N. Titova, Dr. Sci. (Med.), Professor, Director

6–8, Lev Tolstoy St., St Petersburg, 197022

titovaon@spb-gmu.ruhttps://orcid.org/0000-0002-1166-9717КузубоваН. А.KuzubovaN. A.

Kузубова Наталия Анатольевна, д.м.н., заместитель директора по научной работе

197022, Санкт-Петербург, ул. Льва Толстого, д. 6–8

Nataliya A. Kuzubova, Dr. Sci. (Med.), Deputy Director of Science

 

kuzubova@mail.ruhttps://orcid.org/0000-0001-6887-0166ЛебедеваЕ. С.LebedevaE. S.

Лебедева Елена Сергеевна, к.б.н., ведущий научный сотрудник

197022, Санкт-Петербург, ул. Льва Толстого, д. 6–8

Elena S. Lebedeva, Cand. Sci. (Biol.), Leading Researcher

 

osmelena@mail.ruНаучно-исследовательский институт пульмонологии Первого Санкт-Петербургского государственного медицинского университета имени академика И.П. ПавловаРоссияResearch Institute for Pulmonology of the Pavlov First Saint Petersburg State Medical UniversityRussian Federation202522062025091116Copyright © Титова О.Н., Кузубова Н.А., Лебедева Е.С., 20252025Титова О.Н., Кузубова Н.А., Лебедева Е.С.Titova O.N., Kuzubova N.A., Lebedeva E.S.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/9188

В патофизиологии большинства случаев тяжелой, трудно контролируемой бронхиальной астмы центральная роль принадлежит эозинофильному Т2-воспалению. В последние годы исследования были сосредоточены на разработке таргетной антиэозинофильной биологической терапии. На сегодняшний день доступны несколько моноклональных антител, которые блокируют сигнальные пути эозинофильного Т2-воспаления, связываясь со специфическими интерлейкинами или их рецепторами. Для выбора оптимальной лечебной стратегии, обеспечивающей достижение эффективного контроля заболевания и полноценного качества жизни, необходимо, помимо точного фенои эндотипирования астмы, определение биомаркеров-предикторов эффективности биологической терапии и исхода заболевания. Нужны новые биомаркеры для выявления тех пациентов, которые с наибольшей вероятностью будут реагировать на биологические препараты. В обзоре представлен анализ научных публикаций последних лет, посвященных поиску прогностических молекулярных биомаркеров, позволяющих оценить активационный статус эозинофилов и определить выбор конкретного биологического препарата, основываясь на прогнозе возможного исхода заболевания. Систематический поиск проведен в электронных базах данных PubMed, Меdline, Web of Science. Рассматривается возможная прогностическая роль гранулярных цитотоксических молекул (нейротоксина эозинофильного происхождения, эозинофильной пероксидазы, эозинофильного катионного белка), выделяющихся при дегрануляции активированных эозинофилов как индикаторов активационного статуса и предикторов эффективности биологической терапии. Анализ научных исследований показывает, что достаточно высокой прогностической ценностью обладает сывороточный уровень нейротоксина эозинофильного происхождения, доступное измерение которого в периферической крови позволяет идентифицировать субпопуляцию пациентов с высоким активационным статусом эозинофилов и более тяжелой формой бронхиальной астмы и может рассматриваться в качестве биомаркера для определения оптимальной персонализированной биологической терапии. Однако на сегодняшний день, в отсутствие доказательных исследований полезности того или иного молекулярного предиктора клинического ответа на биологическую терапию, первоначальный выбор биологических препаратов определяется опытом и мнением лечащих врачей и экспертов.

Eosinophilic T2 inflammation plays a central role in the pathophysiology of most cases of severe, difficult-to-control asthma. Several monoclonal antibodies are now available that block the signaling pathways of eosinophilic T2 inflammation by binding to specific interleukins or their receptors. In order to select the optimal treatment strategy that ensures effective disease control and adequate quality of life, in addition to accurate asthma pheno-/endotyping, it is necessary to determine biomarkers that predict the effectiveness of biological therapy and disease outcome. New biomarkers are needed to identify those patients who are most likely to respond to biological drugs. The review presents an analysis of scientific publications of recent years devoted to the search for prognostic molecular biomarkers that allow assessing the activation status of eosinophils and determining the choice of a specific biological drug based on the prognosis of the possible outcome of the disease. A systematic search was performed in the electronic databases PubMed, Medline, Web of Science. The possible prognostic role of granular cytotoxic molecules (eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophilic cationic protein) released during degranulation of activated eosinophils as indicators of activation status and predictors of the effectiveness of biological therapy is considered. Analysis of scientific studies shows that the serum level of eosinophil-derived neurotoxin has a quite high prognostic value, the accessible measurement of which in peripheral blood allows identifying a subpopulation of patients with a high activation status of eosinophils and a more severe form of bronchial asthma, and can be considered as a biomarker for determining optimal personalized biological therapy. However, in the absence of evidence-based studies on the usefulness of any given molecular predictor of clinical response to biological therapy, the initial choice of biological agents is determined by the experience and opinions of treating physicians and experts.

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