Biomedical subjects
Publications and source records attributed to L P Alekseev.
The data presented in this paper shows the role of HLA genes and their products HLA-antigens in reproduction. The study is concentrated on new ideas of the role and mechanisms underlyin the functions of both classical and newly determined HLA genes and their products: New data and hypotheses on HLA-molecules' role in "physiological" pregnancy are discussed.
AIM: To study possible immunogenetic HLA markers of chronic viral hepatitides. MATERIAL AND METHODS: Using the reaction of complement-dependent cytotoxicity by Terasaki, we analysed distribution of leukocytic HLA antigens (loci A, B and C) in 179 patients with chronic viral hepatitides B, C and D in Russians and Kazakhs living in the Astrakhan Region. RESULTS: In the Russian population we discovered a significant positive association of CVHB with HLA-B18, HLA-B35, HLA-B40, HLA-Cw3 antigens, and negative one--with HLA-A2. In Kazakhs with CVHB there was a positive association with HLA-A3, HLA-B18 and negative one--with HLA-A11. Alleles HLA-A10, HLA-B35, HLA-B40 and HLA-Cw3 mark CVHC in Russians. HLA-Cw4 specificity acts as protector in development of chronic HCV-infection. A correlation was found between carriage of some specificities and haplotypes of HLA and activity of chronic HBV and HCV infection. A high risk of chronic delta infection in Russians is associated with HLA-B8 and HLA-B35, in Kazakhs--with HLA-B35 and HLA-D40. There are significant associations between CVHB, CVHC, chronic delta infection and some HLA haplotypes. CONCLUSION: A universal role of HLA-B35 specificity in development of CVH irrespective of hepatotropic virus and patients' nationality is shown.
In addition to performing its major physiological function--a control of the immune response, the major gene complex: HLA system, also maintains a human genetic diversity. The latter provides optimal conditions for survival of human being as species. We submit modern data on genome and proteome mechanisms which are principal for maintenance of these functions.
Most parameters of the immune status were found to depend on the HLA-antigens determined in the phenotypes of the human subjects under study. The findings suggest a HLA-transmitted genetic regulation of immune response. Various HLA-markers related to certain parameters of the immune status, were determined. These markers seem to be unique and different for each examined population.
The paper presents the results of recent studies of human major histocompatibility complex. They are due to the progress made at the serological and molecular genetic levels of research and are applied in practical medicine, including in endocrinological and transplantological care. The main prospects of using these achievements in immunogenetics in the treatment of cancer and infectious diseases, including AIDS are defined.
Patients' genotyping of Russian ethnic group with multiple sclerosis (MS) was performed for the first time in two loci of the main complex of histocompatibility: in DR HLA class II (gene DRB1) and in the locus of tumor necrosis factors (TNF). There was no difference in the incidence of alleles groups which correlated with some specificity of DR. Meanwhile TNF-a1 and TNF-a9 alleles were encountered significantly more frequently in patients and TNF-a7 in control group. When all the patients and controls examined were divided into groups in dependence on combination of DR and TNF it was found that relations observed between MS and TNF-a7 and TNF-a9 alleles were displayed much more in individuals which carried alleles of gene DRB1, corresponding to DR15 specificity. These are alleles which are known as the main risk factor of MS in Caucasians. The patients with "protective" TNF-a7 allele were characterized by more favorable course of the disease. Thus highly significant genetic markers were revealed for the first time in region of TNF genes which were associated with increased or decreased risk of MS development at least in Russian ethnic group. There was also possibility of their interaction with group of DR15 alleles of DRB1 gene. One of the markers revealed (TNF-a7) occurred to be bound both with decreased risk of MS and with favorable clinical course, which was observed for genetic markers of MS for the first time. Manifestation of one or another property of TNF-a7 marker depends on the presence of alleles of DRB1 gene which corresponds to DR15 specificity.
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Comparison of two parameters of the peripheral blood mononuclear proliferative response to mitogens (stimulation index, absolute incorporation of radioactive label into proliferating cultures) has shown a discrepancy between the results obtained with the use of these parameters.
HLA-antigens grade I and II were studied by tissue typing in 60 Russians and 40 Georgians suffering from dilated cardiomyopathy (DCMP), and 40 Georgians with virus myocarditis. 267 test-donors Russians and 579 Georgians served as control. Markers of DCMP predisposition were found different for Russians and Georgians: DR4 (relative risk 2.96) and A11 (RR = 3.07), R12 (RR = 5.5), respectively. Georgians have a marker of resistance to DCMP--B35 (RR = 0.15). Antigen B12 marks a severe DCMP course in Georgians. Markers of virus myocarditis predisposition were distinct from those of DCMP: A1 (RR = 3.78) and B27 (RR = 3.62). This shows different etiology of the two diseases. The conclusion is made on nonidentical genetic markers of predisposition and resistance to the same disease in various populations.
Tissue typing was used to study characteristic features of class I and II HLA-antigens distribution in two populations of young IHD patients: Russians (n-32) and Georgians (n-72). Healthy donors (267 Russians and 579 Georgians) served as controls. Genetic markers of IHD predisposition are revealed: for Russians relative risk for B12, DR1 equaled 2.95 and 3.65, respectively, and for Georgians 6.60, 3.02 and 2.33 for B21, Bw22 and DR2, respectively. The differences in markers of IHD predisposition in two populations belonging to the same race suggest than IHD predisposition gene in each population may be bound to various HLA antigen(s). This necessitates study of the markers not only in each race, but in each population as well.
The study of the proliferative and regulatory functions of lymphocytes in patients with lepra of the lepromatous type has shown that at the active stage of the disease both the response of lymphocytes to mitogens and their suppressor functions are decreased. During the regression of the disease these characteristics are restored to the normal level only in patients with the relapse-free course of the disease, while patients with relapses in their medical history retain the low level of such characteristics. It is expedient to use these cell-mediated immunity characteristics as signs permitting the formation of risk groups of patients who may expect the relapse of the disease.
The peculiarities of human leukocyte antigen (HLA) distribution (classes I and II) in young Georgians (72 patients) and Russians (81 patients) with ischaemic heart disease (IHD) were examined by standard tissue-typing methods. The distributions of HLAs in 267 healthy Russian, and 579 healthy Georgian blood donors were taken as controls. The antigens identified as genetic markers of IHD predisposition among Russians were B12 (relative risk, Rr = 2.91), DR1 (Rr = 3.41), and DR4 (Rr = 3.14), for Georgians B21 (Rr = 6.61) was identified. The difference in predisposition markers between these two populations, both belonging to the same race, indicates that IHD predisposition can be linked with different HLAs in different populations.
Tissue typing applied to the Russian population was used to study distribution of HLA antigens, classes I and II, in patients with essential hypertension (EH), coronary heart disease (CHD), hypertrophic cardiomyopathy (HCMP), dilated cardiomyopathy (DCMP) and virus myocarditis (VM). As control use was made of the data on HLA antigen distribution in 267 healthy persons (donors) of the Russian nationality. The genetic markers of the predisposition to the indicated diseases were revealed: in EH, DR 1 (RR-3.56), DR 4 (RR-2.17); in CHD, B 12 (RR-2.91), DR 1 (RR-3.41), DR 4 (RR-3.14); in HCMP, DR 1 (RR-2.25), DR 4 (RR-3.29); in DCMP, DR 4 (RR-3.90); in VM, DR 3 (RR-5.26), DR 4 (RR-3.51). DR 4 turned out to be the common marker of the predisposition to cardiac diseases. Besides, DR 1 was discovered to be the marker of the predisposition to EH and DR 3 to VM. The data obtained may be of importance for the clinical practice in forming risk groups.
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Using a modified model, 16 patients with systemic lupus erythematosus were examined for the activity of nonspecific Con A-induced suppressors with the aid of different test systems. The suppressors of both patients and donors were employed. The proliferation of the test culture lymphocytes appeared to be activated. The immunogenetic abnormalities indicated seem likely to be related to extreme activity of the countersuppressor cells blocking the function of the suppressors, correlating with the clinical picture of the disease.
As many as 34 patients with essential hypertension (EH) and 66 with hypertrophic cardiomyopathy (HCMP) were examined. Concentric hypertrophy of the myocardium was identified in 14 patients with EH and 35 patients with HCMP. Asymmetric hypertrophy of the myocardium was diagnosed in 20 EH patients and 31 HCMP patients. Distribution of class I and II HLA antigens was examined in all the patients. The high rate of DR1 antigen demonstration was established in patients with associated EH and asymmetric hypertrophy of the myocardium. The patients with associated HCMP and hypertrophy of the myocardium showed the high rate of B40 and DR4 antigen demonstration, those with associated HCMP and asymmetric hypertrophy of the myocardium the high rate of DR1 and DR4 antigen demonstration. The data obtained may be of importance for the formation of the groups at risk for the development of the diseases in question and for their differential diagnosis in doubtful cases.
14 Uzbek cousin-marriage families have been immunologically examined. 13 persons have been identified, who are probably homozygous in HLA-D region (the results of the reaction in mixed lymphocyte culture). The members of cousin-marriage families, as compared to healthy Russian donors, had lower proliferative response to phytohemagglutinin and concanavalin A and decreased indexes of concanavalin A-induced suppression and natural killer activity against K562 targets (in children). At the same time natural killer activity in adults, T- and B-lymphocyte content and IgM, IgG and IgA levels are similar to the respective indexes in Russian donors.