mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-FOI-3159mimmun-3159Research ArticleОБЗОРЫREVIEWSОсобенности иммунного ответа на ксеногенные ткани клапанов и заплат сердца: обзор литературыFeatures of immune response to xenogeneic tissues of cardiac valves and patches: Review of literaturehttps://orcid.org/0000-0002-8785-7896ШабалдинА. В.ShabaldinA. V.

д.м.н., доцент, ведущий научный сотрудник лаборатории пороков сердца отдела хирургии сердца и сосудов 

PhD, MD (Medicine), Associate Professor, Leading Researcher, Laboratory of Heart Defects, Department of Heart and Vascular Surgery

weit2007@yandex.ruБлиноваА. В.BlinovaA. V.

клинический ординатор 

Clinical Resident

blinav@kemcardio.ruhttps://orcid.org/0000-0001-8475-4667ЕвтушенкоА. В.EvtushenkoA. V.

д.м.н., заведующий лабораторией пороков сердца отдела хирургии сердца и сосудов

PhD, MD (Medicine), Head, Laboratory of Heart Defects, Department of Heart and Vascular Surgery

ave@kemcardio.ruФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний»РоссияResearch Institute for Complex Issues of Cardiovascular DiseasesRussian Federation20252012202527611811194Copyright © Шабалдин А.В., Блинова А.В., Евтушенко А.В., 20252025Шабалдин А.В., Блинова А.В., Евтушенко А.В.Shabaldin A.V., Blinova A.V., Evtushenko A.V.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/3159

Глобальное исследование показывает, что клапанная болезнь сердца до настоящего времени занимает одно из ведущих мест в структуре смертности от сердечно-сосудистых заболеваний, являясь одной из значимых причин развития сердечной недостаточности, в том числе среди трудоспособного населения. Ксеногенные ткани широко используются в кардиохирургии для изготовления биологических протезов клапанов сердца, а также для сосудистых и внутрисердечных заплат. Современные методики химической обработки ксеногенной ткани, направленные на устранение ее иммуногенности, полностью не удаляют ксеноантигены с ткани. Считается, что остаточные углеводные антигены животных являются триггером иммунного ответа на ксеноткани. В то же время дискуссия о роли иммунного ответа на ксеногенные антигены в индукции воспаления, дисфункции и кальцификации клапанных структур сердца продолжается. Целью настоящего обзора явилось обобщение данных научных исследований, посвященных иммунному реагированию на ксеногенные ткани, и поиску путей преодоления иммунного конфликта. Модификация перикарда крупных животных различными методами не удаляет углеводные эпитопы внеклеточного матрикса и мембран клеток, которые распознаются предсуществующими антителами класса М и G. Высокодинамичное функционирование ксеногенных биологических протезов увеличивает их антигенность за счет уменьшения первичной сшивки внеклеточного матрикса и активации альтернативного пути комплемента с адсорбцией на ксеногенной ткани компонента комплемента iC3b, как опсонина для микро- и макрофагов. Воспалительные эндотипы индивидуумов определяются генетически детерминированным повышенным синтезом тех или иных про- и противоспалительных цитокинов. В частности, для ревматической болезни сердца, как основы формирования патологии нативного митрального клапана сердца, характерно повышение TNFα, IFNγ и IL-6. Все эти цитокины могут быть целями для биологической терапии, направленной на ограничение конституционального воспалительного эндотипа. OMICS-технологии, примененные для различных вариантов деградации биологических ксеногенных протезов клапанов сердца с учетом их имплантации и широким клиническим обследованием пациентов, могут открыть новые варианты иммуновоспалительных эндотипов, приводящих к дисфункции биопротезов, с одной стороны, и выявления таргетных молекул, через которые можно ингибировать антиксеногенный иммунный ответ.

Global studies show that valvular heart disease still takes one of the leading places in the structure of mortality from cardiovascular diseases, being among the major causes of heart failure, including those among the employed population. Xenogeneic tissues are widely used in cardiac surgery, both in biological prosthetic heart valves, and as vascular and intracardiac patches. Modern chemical methods of xenogenic tissue treatment aimed at elimination of its immunogenicity but they do not, however, completely remove xenoantigens from the tissues. The residual carbohydrate antigens are thought to be a trigger of immune response against the animal xenotissues. At the same time, the role of immune response to xenogeneic antigens for induction of inflammation, valve dysfunction, and calcification are under discussion. The aim of this review was to summarize the research data on immune response to xenogeneic tissue implanted into the heart, and to find tools of preventing this immune conflict. Modification of pericardium of large animals by various methods does not entirely remove carbohydrate epitopes from extracellular matrix and cell membranes, which are recognized by pre-existing antibodies of M and G classes. The highly dynamic functioning of xenogeneic biological prostheses increases their antigenicity by reducing the primary cross-linking of extracellular matrix and activating the alternative complement pathway associated with adsorption iC3b complement component on xenogeneic tissue, serving as an opsonin for micro- and macrophages. The inflammatory endotypes of individual patients may be genetically determined by increased synthesis of certain cytokines. In particular, rheumatic heart disease, as a basis for the disorders of mitral heart valves, is characterized by an increase in TNFα, IFNγ and IL-6. Any of these cytokines may be targets for biological therapies aimed at limiting the constitutional inflammatory endotype. The OMICs technologies applied to various studies of biological degradation of xenogeneic heart valve prostheses, their implantation, and wide clinical examination of patients, may help us to find novel variants of immune-inflammatory endotypes leading to dysfunction of bioprostheses, and to identify target molecules for potential inhibition of antixenogeneic immune response.

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