rmtОбщая реаниматологияGeneral Reanimatology1813-97792411-7110FSBI "SRIGR" RAMS10.15360/1813-9779-2024-6-2470rmt-2470Research ArticleОБЗОРЫ И КРАТКИЕ СООБЩЕНИЯREVIEWS & SHORT COMMUNICATIONSГенетический, метаболомный, протеомный полиморфизм и клинические фенотипы сепсисаGenetic, Metabolic, and Proteomic Polymorphisms and Clinical Phenotypes of SepsisКовзельВ. А.KovzelV. A.

119991; ул. Ленинские горы, д. 1; 123182; ул. Пехотная, д. 3; Москва

Victor A. Kovzel

11999; 1 Leninskiye gory Str.; 123182; 3 Pekhotnaya Str.; Moscow

agutnik@mail.ruДавыдоваЛ. А.DavydovaL. A.

119991; ул. Ленинские горы, д. 1; 125367; Иваньковское шоссе, д. 3; Москва

Lyubov A. Davydova

11999; 1 Leninskiye gory Str.; 125367; 3 Ivankovskoe highway; Moscow

agutnik@mail.ruЛапинаТ. А.LapinaT. A.

119991; ул. Ленинские горы, д. 1; Москва

Tatyana A. Lapina

11999; 1 Leninskiye gory Str.; Moscow

agutnik@mail.ruСемушкинаА. А.SemushkinaA. A.

127994; Рахмановский пер, д. 3; ГСП-4, г. Москва

Anastasia A. Semushkina

127994; 3 Rakhmanovsky per.; GSP-4; Moscow

agutnik@mail.ruГутниковА. И.GutnikovA. I.

Алексей Иванович Гутников

119991; ул. Ленинские горы, д. 1; 125367; Иваньковское шоссе, д. 3; Москва

Alexey I. Gutnikov

11999; 1 Leninskiye gory Str.; 125367; 3 Ivankovskoe highway; Moscow

agutnik@mail.ruМосковский государственный университет им. М. В. Ломоносова; Городская клиническая больница №52 Департамента здравоохранения г. МосквыРоссияM. V. Lomonosov Moscow State University; City Clinical Hospital № 52, Moscow City Health DepartmentRussian FederationМосковский государственный университет им. М. В. Ломоносова; Национальный медицинский исследовательский центр «Лечебно-реабилитационный центр» Минздрава РоссииРоссияM. V. Lomonosov Moscow State University; National Medical Research Center, Center for Treatment and RehabilitationRussian FederationМосковский государственный университет им. М. В. ЛомоносоваРоссияM. V. Lomonosov Moscow State UniversityRussian FederationРоссийский университет медицины Минздрава РоссииРоссияRussian University of Medicine, Russian Ministry of HealthRussian Federation2024191120242063653Copyright © Ковзель В.А., Давыдова Л.А., Лапина Т.А., Семушкина А.А., Гутников А.И., 20242024Ковзель В.А., Давыдова Л.А., Лапина Т.А., Семушкина А.А., Гутников А.И.Kovzel V.A., Davydova L.A., Lapina T.A., Semushkina A.A., Gutnikov A.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.reanimatology.com/rmt/article/view/2470

   Гетерогенность групп пациентов с сепсисом является нерешенной проблемой, не позволяющей выработать оптимальную стратегию терапии и предложить инструменты прогноза течения заболевания. Классификация гетерогенной популяции пациентов с сепсисом по молекулярным эндотипам, а также мультиомиксное профилирование пациентов с сепсисом определяет возможность вплотную подойти к вопросам персонализированного лечения. Изучение геномики иммунного ответа, метаболомного и протеомного профиля пациентов с сепсисом позволяет провести клиническое фенотипирование гетерогенной популяции, а также выработать прецизионный подход при диагностике, прогнозировании и терапии пациентов с сепсисом и септическим шоком.

   Цель обзора

   Цель обзора: показать комбинации подтипов сепсиса на основании анализа геномного, метаболического и протеомного профиля пациентов и представить новейшие подходы к преодолению гетерогенности групп пациентов с сепсисом: мультиомиксное эндотипирование и клиническое фенотипирование, позволяющие улучшить возможности таргетной терапии и оптимизировать диагностические и терапевтические подходы.

   Поиск информации проводили с использованием баз данных PubMed, по ключевым словам: «sepsis omics», «sepsis endotypes», «sepsis heterogeneity» без языковых ограничений. Из более чем 300 источников для анализа отобрали 120, которые в наибольшей степени соответствовали цели обзора. Из них более 50 % были опубликованы в течение последних пяти лет. Критерием исключения источников служило их несоответствие задачам обзора и малая информативность. В обзоре представили различные категории иммунного ответа, значимость фактора гетерогенности популяции пациентов на терапевтические воздействия, современные взгляды на фенотипирование пациентов с сепсисом. Несмотря на ограничения, связанные с организацией централизованного сбора клинической информации, кластерного анализа большого массива данных, роль геномики, метаболомики и протеомики иммунного ответа при сепсисе в прогнозе и лечении заболевания постепенно становится доминирующей. Установление связей между всеми этими элементами и попытка клинического фенотипирования сепсиса, в том числе с анализом подтипов, по-видимому, в ближайшее время будет определяющим фактором в поиске персонализированных подходов к лечению.

  Заключение

  Заключение. В настоящее время общепризнанной целью лечения пациентов с сепсисом является его раннее выявление и начало терапии для предотвращения развития необратимого септического шока и синдрома полиорганной недостаточности. Персонализированная оценка генетического, метаболомного и протеомного профиля пациента представляется интересным и перспективным направлением поиска новых стратегий лечения при сепсисе.

   The heterogeneity of sepsis patient populations remains an unresolved issue, hindering the development of effective therapeutic strategies and disease prognostic tools. Classification of diverse sepsis patients by molecular endotypes, together with multi-omics profiling, enables a more personalized treatment approach. Studying the immune response, genomic, metabolomic and proteomic profiles of sepsis patients will enable clinical phenotyping of this diverse population and the development of a precision approach to the diagnosis, prognosis and treatment of sepsis and septic shock.

   The aim of the review was to discuss sepsis subtypes as identified by profiling of patient genomic, metabolic, and proteomic data and present the latest approaches addressing the heterogeneity of sepsis patient populations, such as multi-omics endotyping and clinical phenotyping, which may aid in targeted therapy and optimization of diagnosis and therapy.

   The keywords «sepsis omics», «sepsis endotypes», and «sepsis heterogeneity» were used to search PubMed databases without language restrictions. From over 300 sources, 120 were selected for analysis as being most relevant to the aim of the review. More than half of these were published within the last five years. Criteria for excluding sources were their inconsistency with the aims of the review and their low informativeness. This review discusses the different types of immune responses, the impact of patient population heterogeneity on therapeutic interventions, and current perspectives on phenotyping sepsis patients. Despite the limitations of centralized collection of clinical information, cluster analysis of large data sets and the role of immune response genomics, metabolomics, and proteomics are beginning to dominate the prognosis and treatment of sepsis. Establishing links between all these elements and attempting clinical phenotyping of sepsis, including subtype analysis, appear to be critical in the search for personalized treatment approaches in the near future.

   Conclusion. Currently, the widely accepted goal in sepsis management is early detection and initiation of therapy to prevent the development of irreversible septic shock and multiorgan failure syndrome. Personalized genetic, metabolomic and proteomic profiling of the patient seems to be an intriguing and promising avenue in the search for new treatment strategies in sepsis.

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