IMMUNOGENETIC CHARACTERISTICS OF THE HLA SYSTEM IN PATIENTS WITH EARLY AND LATE CHD AND PERMANENT MYOCARDIAL INFARCTION

Lomakovsky A.N., Minchenko J.N., Gavrilenko T.I., Pidgaina O.A.

Summary. Introduction. The hereditary component of this pathology includes gene polymorphism for different genetic systems, which are involved both in the development of ischemic heart disease and the development of its complications. The aim of the study was to determine the possibility of using immunogenetic parameters as prognostic markers of early development and complications of coronary artery disease by comparing the phenotypic and genotypic characteristics of the HLA system with the appearance of the first clinical manifestations of coronary artery disease at different ages of patients and with the development of myocardial infarction. Object and research methods. 58 patients with stable coronary artery disease were examined. The control group was matched by 50 healthy individuals. The material for the immunological study was peripheral venous blood. The typing of HLA antigens was performed by the complement-dependent cytotoxicity test in the microlimphocytotoxic test. Typing was carried out on 19 HLA-sera of locus A and 36 — locus B. Genotyping of allelic variants of HLA class I (loci A, B, C), II class (loci DRB1, DQA1, DQB1) was carried out by a molecular genetic method. Levels of tumor necrosis factor α, interleukin-6 and 8, interferon γ in blood serum and culture of mononuclear cells (monocytes and lymphocytes), levels of highly sensitive C-reactive protein and antibodies to oxidized low density lipoproteins in serum were determined by solid-phase enzyme-linked immunosorbent assay. The proliferative nonspecific activity of lymphocytes to the mitogen phytohemagglutenin and the specific sensitization of lymphocytes to antigens of the vascular wall was assessed in the blast transformation reaction. Research results. Immunogenetic characteristics of the phenotype and genotype of the HLA system affect the development of ischemic heart disease. The HLA-specificity of the genetic control of the immune response is associated with the propensity and tolerance for the early onset of clinical manifestations of coronary artery disease and the development of myocardial infarction. A positive and negative relationship of some HLA antigens and HLA genes with the production of inflammatory mediators, sensitization of lymphocytes to the tissues of the vascular wall, and the level of antibodies to oxidized LDL has been shown. Conclusions. The presence of certain class I HLA antigens and class II HLA genes may indicate a genetic predisposition and genetic resistance to ischemic heart disease. The early onset of clinical manifestations of coronary artery disease (up to 45 years of age), as well as myocardial infarction, are associated with HLA-specificities of the genetic control of the immune response. A positive and negative relationship of some HLA antigens and HLA genes with the production of inflammatory mediators, proliferative activity of T-lymphocytes, sensitization of lymphocytes to the tissues of the vascular wall and the level of antibodies to oxidized LDL was revealed.

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