Features of immune response to xenogeneic tissues of cardiac valves and patches: Review of literature

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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