mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-IFO-3254mimmun-3254Research ArticleОБЗОРЫREVIEWSИммунологические особенности фенотипов и эндотипов сепсисаImmunological features of sepsis phenotypes and endotypeshttps://orcid.org/0000-0001-9647-1322ПотаповаМ. Б.PotapovaM. B.

Потапова Мария Борисовна – к.м.н., научный сотрудник лаборатории молекулярной иммунологии.

105064, Москва, Малый Казенный пер., 5a. Teл.: 8 (929) 927-52-35

Maria B. Potapova - PhD (Medicine), Researcher, Laboratory of Molecular Immunology.

5a Maly Kazenny Lane Moscow 105064 Phone: +7 (929) 927-52-35

ptpv.msh@gmail.comhttps://orcid.org/0000-0001-5808-2246ЗверевВ. В.ZverevV. V.

Зверев В.В. – д.б.н., профессор, академик РАН, научный руководитель, ФГБНУ «НИИВС имени И.И. Мечникова»; заведующий кафедрой микробиологии, вирусологии и иммунологии ФГАОУ ВО «Первый МГМУ имени И.М. Сеченова» Министерства здравоохранения РФ (Сеченовский Университет).

Москва

PhD, MD (Biology), Professor, Full Member, Russian Academy of Sciences, Research Supervisor, I. Mechnikov RIVS; Head, Department of Microbiology, Virology and Immunology, I. Sechenov First MSMU (Sechenov University).

Moscow

vitalyzverev@outlook.comhttps://orcid.org/0000-0002-4288-3791БабаевМ. А.BabaevM. A.

д.м.н., главный научный сотрудник отделения реанимации и интенсивной терапи II.

Москва

PhD, MD (Medicine), Chief Researcher, Intensive Care Unit II.

Moscow

nrcs@med.ruhttps://orcid.org/0000-0002-5620-1843БогдановаЕ. А.BogdanovaE. A.

к.м.н., доцент кафедры микробиологии, вирусологии и иммунологии.

Москва

PhD (Medicine), Associate Professor, Department of Microbiology, Virology and Immunology, I. Sechenov First Moscow State Medical University (Sechenov University).

Moscow

bogdanova_e_a_1@staff.sechenov.ruhttps://orcid.org/0000-0003-1773-1291ГриньО. О.GrinO. O.

к.м.н., младший научный сотрудник отделения реанимации и интенсивной терапии II.

Москва

PhD (Medicine), Junior Researcher, Intensive Care Unit II.

Moscow

grin_oksana@mail.ruhttps://orcid.org/0000-0002-6630-4838СеменоваИ. Б.SemenovaI. B.

д.м.н., ведущий научный сотрудник лаборатории терапевтических вакцин.

Москва

PhD, MD (Medicine), Leading Researcher, Laboratory of Therapeutic Vaccines.

Moscow

ibsemenova@yandex.ruhttps://orcid.org/0000-0003-4334-1473МеремьянинаЕ. А.MeremianinaE. A.

к.м.н., научный сотрудник лаборатории молекулярной иммунологии.

Москва

PhD (Medicine), Researcher, Laboratory of Molecular Immunology.

Moscow

ekaterina@meremianina.ruhttps://orcid.org/0000-0003-1757-8389СвитичО. А.SvitichO. A.

д.м.н., профессор, академик РАН, директор, заведующая лабораторией молекулярной иммунологии ФГБНУ «НИИВС имени И.И. Мечникова»; профессор кафедры микробиологии, вирусологии и иммунологии ФГАОУ ВО «Первый МГМУ имени И.М. Сеченова» Министерства здравоохранения РФ (Сеченовский Университет).

Москва

MD, PhD (Medicine), Professor, Full Member, Russian Academy of Sciences, Director, Head of the Laboratory of Molecular Immunology, I. Mechnikov RIVS; Professor, Department of Microbiology, Virology and Immunology, I. Sechenov First MSMU (Sechenov University).

Moscow

svitichoa@yandex.ruФГБНУ «Научно-исследовательский институт вакцин и сывороток имени И.И. Мечникова»РоссияI. Mechnikov Research Institute for Vaccines and SeraRussian FederationФГБНУ «Научно-исследовательский институт вакцин и сывороток имени И.И. Мечникова»; ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения РФ (Сеченовский Университет)РоссияI. Mechnikov Research Institute for Vaccines and Sera; I. Sechenov First Moscow State Medical University (Sechenov University)Russian FederationФГБНУ «Российский научный центр хирургии имени академика Б.В. Петровского»РоссияB. Petrovsky Russian Research Center for SurgeryRussian FederationФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения РФ (Сеченовский Университет)РоссияI. Sechenov First Moscow State Medical University (Sechenov University)Russian Federation202614022026281920Copyright © Потапова М.Б., Зверев В.В., Бабаев М.А., Богданова Е.А., Гринь О.О., Семенова И.Б., Меремьянина Е.А., Свитич О.А., 20262026Потапова М.Б., Зверев В.В., Бабаев М.А., Богданова Е.А., Гринь О.О., Семенова И.Б., Меремьянина Е.А., Свитич О.А.Potapova M.B., Zverev V.V., Babaev M.A., Bogdanova E.A., Grin O.O., Semenova I.B., Meremianina E.A., Svitich 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.mimmun.ru/mimmun/article/view/3254

Сепсис представляет собой гетерогенное и жизнеугрожающее состояние, обусловленное дисрегуляцией иммунного ответа на инфекцию. Наиболее тяжелой формой является септический шок, характеризующийся снижением артериального давления, ухудшением перфузии тканей и гипоксией. Несмотря на развитие антибактериальной и интенсивной терапии, заболеваемость и смертность при сепсисе остаются высокими, что подчеркивает актуальность углубленного изучения его патогенеза. В последние годы акцент в научных исследованиях сместился с клинической симптоматики к анализу его иммунных и молекулярных механизмов, что позволило выделить различные фенотипы и эндотипы заболевания. Фенотипы сепсиса определяются на основании клинических проявлений и биомаркеров. В основе же эндотипов лежат молекулярные механизмы, включая экспрессию генов иммунного ответа. В данной статье рассмотрены ключевые аспекты врожденного и адаптивного иммунного ответа при сепсисе, включая активацию провоспалительных цитокинов, развитие коагулопатий, нарушение целостности эндотелия и регуляции микрососудистого кровотока. Кроме того, подчеркивается значение таких механизмов, как гипервоспаление, одновременное развитие иммуносупрессии и функционального истощения иммунокомпетентных клеток. В связи с этим, иммунологические биомаркеры рассматриваются как перспективный инструмент для стратификации пациентов, прогнозирования клинических исходов и проведения персонализированной терапии. Также рассмотрены современные подходы в иммунодиагностике, включая количественную оценку уровней цитокинов и определение маркеров дисфункции врожденного иммунитета. Таким образом, современное понимание сепсиса как иммунологически гетерогенного синдрома существенно расширяет представление о его патогенезе. Наряду с классической концепцией «воспаления, сменяющегося иммуносупрессией», все большее значение приобретает идея одновременного сосуществования этих состояний, что требует пересмотра подходов к диагностике и терапии. Кроме того, стратификация пациентов на основе клинических фенотипов и молекулярных эндотипов позволяет более точно прогнозировать течение заболевания и ответ на лечение. В настоящее время иммунодиагностика приобретает ключевую роль в персонализированном подходе к лечению пациентов с сепсисом.

Sepsis is a heterogeneous and life-threatening condition caused by a dysregulated immune response to infection. The most severe form of sepsis is septic shock, characterized by arterial hypotension, impaired tissue perfusion, and hypoxia. Despite new findings in antimicrobial and intensive care therapy, the incidence and mortality rates of sepsis remain high, which underscores the relevance of further studies on its pathogenesis. In recent years, the research has shifted from clinical signs to analysis of immunological and molecular mechanisms, which allowed to identify specific phenotypes and endotypes of the disease. Sepsis phenotypes are based on clinical manifestations and biomarkers, whereas its endotypes are defined by molecular mechanisms, including immune gene expression patterns. This article reviews key aspects of the innate and adaptive immune responses in sepsis, including activation of proinflammatory cytokines, development of coagulopathies, deterioration of endothelial integrity and microvascular regulation. Moreover, the potential mechanisms, e.g., hyperinflammation, simultaneous development of immunosuppression, and functional exhaustion of immunocompetent cells are highlighted. Thus, immunological biomarkers are considered a promising tool for patient‘s stratification, prognosis prediction and personalized therapy. Current immunodiagnostic methods are also discussed in this article, including quantitative analysis of cytokine levels and assessment of innate immune dysfunction markers. Hence, current understanding of sepsis as an immunologically heterogeneous syndrome enables researchers to expand existing concepts of its pathogenesis. In contrast to classical concept based on a shift from inflammation to immune suppression, the novel results suggest a simultaneous presence of both processes in the same patient, making it necessary to reconsider the existing diagnostic and therapeutic approaches.

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