[Immunogenetics of type 1 diabetes mellitus--from fundamental ideas to medical practice].

The review of studies of Russian researchers on theoretical and practical aspects of genetic predisposition to type 1 diabetes associated with immunity: HLA and not HLA genes. Most important for practical public health outcomes are evidence that HLA-genetic predisposition to type 1 diabetes is associated with the DRB1-genotype, consisting entirely of variants DRB1-genes associated with the development of T1D. It was also established that CTLA4 gene has an independent predictive value for T1D.

[Immune response genes products in human physiology].

Current data on physiological role of human immune response genes' proteomic products (antigens) are discussed. The antigens are specified by a very high level of diversity that mediates a wide specter ofphysiological functions. They actually provide integrity and biological stability of human as species. These data reveal new ideas on many pathological processes as well as drafts new approaches for prophylaxis and treatment.

[Regulatory role of the immune system in the organism].

The paper presents modern idea of regulatory role of the human immune system in performing a number of physiological functions including intercellular interactions, reproductive process, and forming of protection against external and internal aggression. Significance of the immune system is considered and substantiated, that of genes of the human immune response in particular in provision of human survival as a biological species.

[The physiological role of the HLA system and the population aspects].

Identification of HLA genes and further identification of their biological role were among major achievements of medical-biological science in XX century. Several Nobel Prizes awarded in that field of science proved their importance. The end of XX Century and beginning of the XXI century were marked by introduction of molecular genetic methods in research. The contributed to development and revision of current ideas of physiological role of HLA supporting genetic homeostasis and human survival as species. Moreover they prompted to review the existing concepts of inter- and intra-populational polymorphism among HLA-frequencies.

[The use of achievements in human molecular immunogenetics in the management of type 1 diabetes mellitus].

New original data are presented on the use of achievements in human molecular immunogenetics in the management of type 1 diabetes mellitus. They include materials allowing for the prediction of the development of the disease at the population, family, and individual levels along with novel approaches to its radical treatment by the reconstitution of the lost glucose tolerance. The reported data may find wide application in current clinical practice. They open up new prospects for the enhancement of efficacy of prognosis, diagnosis, and treatment of type 1 diabetes mellitus and other autoimmune diseases.

[siRNA-mediated inhibition of respiratory syncytial virus replication].

The effect of siRNA against respiratory syncytial virus (RSV) was investigated in the cultured cells. MA104 cells were inoculated by RSV and transfected by different variants of siRNA against RSV phosphoprotein (P) mRNA or non-specific siRNA as a control. The inhibition of RSV was assessed by microscopically studying the cells, titrating the virus, and estimating viral RNA quantity in the culture supernatants by real-time polymerase chain reaction (PCR). The most potent variants of siRNA caused an up to 8-day delay of microscopically detectable syncytium generation to 8 days, an up to 280-fold decrease in viral titers, and an up to 40-fold reduction in viral RNA quantity in the supernatants, as compared to the controls (p < 0.001). RSV mRNA is a suitable target for siRNA-mediated RSV replication inhibition, promising an advance in the treatment of RSV infection.

[New ideas of the physiological role of the genes' HLA in reproductive process].

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.

[Immunogenetic HLA markers of chronic viral hepatitis].

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.

[Physiology of immune response genes]. / Fiziologiia genov immunnogo otveta.

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.

[Frequency of genes speA, speB, and speC in Streptococcus pyogenes strains and the identification of the infective agent by polymerase chain reaction]. / Chastota vstrechaemosti genov speABC v shtammakh Streptococcus pyogenes i identifikatsia vosbuditelia s pomoshch'iu PTSR.

In cultures of S. pyogenes isolated from patients and carriers in different territories of the Russian Federation the genes of erythorogenic toxins A, B and C (speA, speB and specC) were detected. The possibility of the identification of S. pyogenes by means of PCR on the basis of primers to erythrogenic toxin B was determined. Gene speB was detected in all S. pyogenes cultures under study and proved to be species specific. Genes speA and speC were detected, respectively, in 29.4% and 9.35% of the S. pyogenes cultures under study. A test system for the identification of S. pyogenes on the basis of primers to gene speB was developed. The prospects for the detection of genes speA and speC for intraspecific typing of this infective agent were evaluated.

[Interethnic differences in the genetic control of the human immune status]. / Interétnicheskie razlichiia v geneticheskom kontrole immunnogo statusa cheloveka.

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.

[Immunogenetic achievements for medicine]. / Dostizheniia immunogenetiki - meditsine.

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.

[Genetic predisposition factors for multiple sclerosis (based on the data from genotyping patients of the Russian ethnic group)]. / Faktory geneticheskoi predraspolozhennosti k rasseiannomu sklerozu (po dannym genotipirovaniia bol'nykh russkoi étnicheskoi gruppy).

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.

[Dynamics of disorders of cellular and humoral immunity parameters in patients with insulin-dependent diabetes mellitus]. / Dinamika narushenii pokazatelei kletochnogo i gumoral'nogo immuniteta u bol'nykh insulinzavisimym sakharnym diabetom.

Analysis of immunocompetent cell subsets in peripheral blood of patients with insulin dependent diabetes mellitus (IDDM) and the determination of sICA-autoantibodies in their sera were performed by flow rate cytometry and compared to healthy donors and patients with noninsulin-dependent diabetes mellitus (NIDDM). It was shown that newly diagnosed IDDM was characterized by predominant disturbances of humoral immunity, and disease progression was mainly accompanied by cellular immunity disturbances. Exogenous insulin was one of the causes of such disturbances. A tendency to normalization of cellular rather than humoral immunity was observed after the onset of human monocompetent therapy of IDDM patients. It is likely that the appearance in the peripheral blood of activated T-lymphocytes accompanied by sICA-autoantibodies and increased mature B-lymphocytes and NK-cells counts corresponds to increased ADCC against pancreatic beta cells in IDDM development.

[Immunologic indices in a varying course of lepromatous leprosy]. / Immunologicheskie pokazateli pri razlichnom techenii lepromatoznoi lepry.

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.

[HLA-associated susceptibility to ischemic heart disease]. / Assotsiirovannaia s HLA predraspolozhennost' k ishemicheskoi bolezni serdtsa.

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.