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BACKGROUND: Type 1 diabetes mellitus (DM1) is a chronic autoimmune disease characterized by damage to insulin–producing cells of the pancreas, which eventually leads to the need for insulin replacement therapy. The clinical picture of DM1 is heterogeneous: the onset of the disease at an early age is characterized by a more acute manifestation and rapid depletion of residual insulin secretion. Variations of HLA genes can probably determine the clinical features of the course of DM1. To date, age-related features of HLA genes have been established in various populations, at the same time, such data are not available in the Russian population.AIM: To study the effect of HLA genes on predisposition to DM1 in preschool age.MATERIALS AND METHODS: A single-center, one-stage study, including data from 885 children (1 year — 18 years old) with previously diagnosed DM1 who are on intensified insulin therapy. The study participants’re divided into two groups: a group with a manifestation of DM1

Relevance. It is known that the immune response to the administration of immunobiological drugs is variable and depends on the individual characteristics of the organism. Host immunogenetic factors have a significant impact on the effectiveness of vaccination. In this study, the frequencies of alleles of the HLA class I (HLA-A, B, C) and class II genes (HLA-DRB1, DPB1, DQB1) were studied in groups of participants with different levels of antibodies (anti-HBs) after vaccination against viral hepatitis B. Aims of the work was to determine the possible relationship between alleles of HLA genes and the intensity of post-vaccination immunity against hepatitis B. Materials and methods. The study included 271 apparently healthy adults who were divided into 3 groups depending on the specific concentration of post-vaccination antibodies (anti-HBs) using ELISA. All calculations were made relative to the groups anti-HBs >100 mIU/ml (n=82), 10-100 mIU/ml (n=98) (protective antibody level) and anti-HBs

Infection is inconceivable without T cells. T cells not only eliminate virus-infected cells and participate in the formation of immunological memory, but also indirectly modulate the humoral response through the selection and maintenance of specific B cells. The T-cell receptor (TCR) recognizes processed antigen presented on the surface of cells in the MHC of one of two classes. Thus, the formed TCR repertoire reflects the history of encountered antigens through the prism of the specific organism with a particular set of MHC. To investigate changes in the TCR repertoire in response to acute viral infection, we utilized a yellow fever vaccination model. The yellow fever vaccine has been a benchmark for both safety and efficacy for over half a century. The vaccine is based on a live attenuated virus, allowing the study of the immune response under conditions closely to the viral infection. The yellow fever-specific T-cell response to immunodominant peptides presented on HLA-A02 is well studied, but experiments with HLA-A02-negative donors are still lacking. The aim of this study was to examine the dynamics of changes in the T-cell repertoire structure that occur in response to yellow fever vaccination in a donor without the HLA-A02 allele. We found that the overall T-cell response dynamics were similar to that in HLA-A02-positive donors: vaccination led to rapid expansion of yellow fever-reactive clones by day 14. Despite the absence of a known immunodominant epitope for HLA I alleles in this donor, the immune response also shifted towards CD8⁺ T cells, with increasing of the CD8⁺ clones fraction by day 53. The amino acid sequences of CDR3 TCRb yellow fever specific clones formed a stable cluster by CD4⁺ T cells, further confirming the presence of novel immunogenic epitopes.

Next generation sequencing (NGS) allows high-resolution and allelic HLA-typing. The most common platform is MiSeq (Illumina, USA). Currently, the maintenance of this device is difficult, which has necessitated the search for analogues that are not inferior in capacity and quality of HLA-typing. The purpose of our study was a comparative analysis of the results of HLA-typing by NGS using the MiSeq (Illumina, USA) and FastaSeq 300 (Gene-Mind, China) platforms. The study included DNA samples of hematopoietic stem cell (HSC) donors: 12 samples were obtained and analyzed at the FSBI RosNIIGT FMBA of Russia and 24 samples at the National Medical Research Center for Hematology of the Ministry of Health of the Russian Federation. HLA typing of all samples was performed twice: using a MiSeq sequencer and a FastaSeq 300 sequencer. The results of HLA-typing of 12 samples from the FSBI RosNIIGT FMBA of Russia, obtained on two platforms, coincided. DRB1 allele of one sample was achieved as group P with MiSeq, but as group G with FastaSeq 300. The results of HLA-typing of 24 samples from the National Medical Research Center for Hematology of the Ministry of Health of the Russian Federation, obtained on two platforms, coincided. However, differences in the level of resolution of HLA-typing were observed for 10 samples. A higher level of resolution with using MiSeq was observed for genes: B – 2 cases; C, DRB3, DRB4 – 3 cases each. When using FastaSeq 300, a higher level of resolution was achieved a little more often and was established for the genes: DRB1 – 4, DQB1 – 7, DPA1 – 10 cases. Differences in the level of resolution of HLA-typing for some samples are not critical, since high-resolution typing results are currently used to select HSC donor-recipient pairs. Our study indicated the possibility of effectively using the FastaSeq 300 for HLA-typing.

T-cell immune response is extremely important in protecting human body from diverse viral infections. It is known that it can ensure viral clearance and complete recovery in patients with humoral immunodeficiency. COVID-19 patients were found to have T-cell response primarily directed against SARS-CoV-2 structural S, M, N, E proteins, with nucleocapsid protein being most conserved. To assess patients immunity against coronavirus infection and evaluate an effectiveness of vaccine candidates, it is necessary to develop an optimal diagnostic antigen to evaluate arising T-cell response against SARS-CoV-2 antigenic determinants. A diagnostic test to determine host specific susceptibility to SARS-CoV-2 infection should target conserved regions of global SARS-CoV-2 variants. The study was aimed to develop a structure of an antigen bearing conserved and immunogenic sequences derived from SARS-CoV-2 structural proteins and to obtain an Escherichia coli producer strain containing a recombinant protein to be subsequently used for assessing antiviral T-cell immunity. Developing of the antigen was performed in silico: TepiTool and NetMHCIIpan were used to predict and identify high affinity epitopes spanning SARS-CoV-2 E, M, N, S proteins and MHC II binding. Several variants of recombinant antigen proteins were constructed, from which one was selected based on its physicochemical properties: isoelectric point, hydrophobicity index and aliphatic index, as well as 3D representation built by using the I-TASSER. The sequence was synthesized and cloned into the pET24a(+) vector. The resulting plasmid pCorD_PS was transformed into E. coli DH5 followed by Rosetta (DE3). The strain-producer of the recombinant E. coli protein CorD_PS was assessed for the presence and stability of IPTG-induced antigen protein expression and elimination of recombinant coronavirus antigen-bearing plasmid. Based on the study data, an antigen was developed consisting of conserved regions from SARS-CoV-2 S, M, N, E proteins. A 53 kDa recombinant protein was predicted to be stable in aqueous solutions with isoelectric point of 9.56 potentially allowing to simplify protein purification from E. coli cells. Plasmid DNA pCorD_PS (6695 bp) encoding final recombinant coronavirus antigen cloned into pET24a(+) vector was obtained. A stable, productive E. coli CorD_PS strain was obtained. The obtained strain-producer resulting in recombinant E. coli CorD_PS antigen is stable allowing to move on to design antigen purification technique and further develop SARS-CoV-2-specific diagnostic test system.

Idiosyncratic drug-induced liver injury (iDILI) is a rare and poorly predictable adverse drug reaction that may lead to death or liver transplantation in severe cases.The aim of the study was to review contemporary concepts of the immune-mediated pathogenesis of iDILI and possible ways to predict and prevent the risk of developing this condition.The liver is characterised by high immune tolerance due to a complex of mechanisms involving various cells (antigen-presenting cells, T-cells), cytokines, and other molecules, which prevents severe immune responses to xenobiotics entering the body. Previous research has shown that iDILI results from a combination of multiple synergistic unfavourable factors that impair liver immune tolerance at different levels. These factors include the hepatotoxicity-associated chemical properties of medicines and the individual characteristics of the patient, including the genetically determined structure and function of the adaptive immune system components. Since iDILI has a multilevel and multifactor pathogenesis, it is difficult to determine a risk biomarker for a particular medicine. According to the literature review, the risk of hepatotoxicity of a drug candidate and/or a metabolite can be reduced at the preclinical level by assessing the ability to cause mitochondrial damage, form non-covalent bonds, produce reactive oxygen species, and release damage-associated molecular patterns (DAMPs). The association of iDILI with gene polymorphisms in patients receiving certain medicines has a high negative predictive value and can be used in clinical practice to rule out iDILI or identify hepatotoxic medicinal products in polypharmacy. The identification of the allele combinations associated with an increased risk of iDILI seems promising for enhancing the predictive value of genetic studies and may be used in personalised medicine.

The genetic variability of population may explain different individual immune responses to the SARS-CoV-2 virus. The use of genome- and peptidome-based technologies makes it possible to develop vaccines by optimizing the target antigens. The computer modeling methodology provides the scientific community with a more complete list of immunogenic peptides, including a number of new and cross-reactive candidates. Studies conducted independently of each other with different approaches provide a high degree of confidence in the reproducibility of results. Most of the effort in developing vaccines and drugs against SARS-CoV-2 is directed towards the thorn glycoprotein (protein S), a major inducer of neutralizing antibodies. Several vaccines have been shown to be effective in the preclinical studies and have been tested in the clinical trials to combat the COVID-19 infection. This review presents the profile of in silico predicted immunogenic peptides of the SARS-CoV-2 virus for the subsequent functional validation and vaccine development, and highlights the current advances in the development of subunit vaccines to combat COVID-19, taking into account the experience that has been previously achieved with SARS-CoV and MERS-CoV. The immunoinformatics techniques reduce the time and cost of developing vaccines that together can stop this new viral infection.

The main histocompatibility complex — HLA system (Human Leukocyte Antigens) is among the most important genetic factors determining response of humans to infectious agents. The key role that HLA molecules play in immune response is to present the pathogen-derived peptides. Enormous molecular variability of HLA alleles in human populations have attracted close attention and became the basis for numerous studies aimed at evaluating the role of HLA genotypes for individual features of immune response to COVID-19, the new infection caused by SARS-CoV-2 β-coronavirus. Many studies have focused on search of specific alleles associated with both susceptibility and resistance to this disease. Separate HLA patterns were reported already. These patterns may be either universal to several populations, or rather peculiar, since distribution of HLA genes is different for various populations, depending on the living conditions, including specific protection from environmental pathogens. Therefore, it is evident that individual effects of HLA genotype upon occurrence and course of SARS-CoV-2 infection should be performed in comparison with the HLA distribution among the residents of appropriate region. The objective of this study was to compare the distribution of HLA-A*, B*, DRB1* allele groups, and to analyze the frequencies of HLA-AB-DRB1 haplotypes in subjects with COVID-19 (n = 138), compared with the control group presented by residents of the North-Western Russia (n = 1456). The most significant differences between COVID-19 patients compared with a group from control population were revealed for the groups of HLA-A* alleles: the frequencies of HLA-A*02 and HLA-A*26 were significantly reduced (39.86% versus 51.72%, χ2 = 7,58, and 4.35% versus 9.07%, χ2 = 4.17, respectively). At the same time, the frequency of HLA-A*29 was increased more than 2-fold (5.80% versus 2.47%, χ2 = 4.03). This finding suggests that the allele groups A*02 and A*26 are associated with reduced likelihood of the disease, while A*29, is an apparent factor predisposing for susceptibility to the disease. It was found that occurrence of definite HLA haplotypes, including the A*02 allele group, is less common in persons who have undergone COVID-19, and are ranged at the 4th, 7th and 10th positions in frequency, while in the population control group such HLA haplotypes took the 3rd, 4th, 7th and 8th places. Further evaluation of the HLA gene polymorphism will allow to understand the predetermined immunogenetic basis for susceptibility, as well as clinical severity of COVID-19.

Next generation sequencing is used to determine full-length sequences of HLA genes at the 4-field (allelic) resolution. The study was aimed at determining frequency and diversity of HLA alleles in a cohort of blood donors from the Registry of the National Research Center for Hematology who design ated themselves as Russians (including some not routinely typed variations in HLA gene regions). The studied population consisted of 1510 donors. HLA typing was performed by next generation sequencing. Libraries were performed with AllType NGS Amplification Kits (One Lambda, USA) and sequenced using MiSeq (Illumina, USA). Data analysis used the TypeStream Visual Software V2.0.0.68 (One Lambda, USA) and IPD-IMGT/HLA database 3.40.0.1. Arlequin 3.5 software was used for estimation of allele and haplotype frequencies, deviation from Hardy-Weinberg equilibrium. 82 HLA-A, 156 HLA-В and 85 HLA-С alleles were identified with four-field resolution. 45 HLA-DRB1 and 18 HLA-DQB1 alleles were identified with 2-3-field resolution. Considerable HLA diversity was found among the donors self-designated as Russians: the population had large numbers of distinct alleles at each HLA gene, high percentage of alleles (25-32% of HLA class I) were revealed only once. Sufficient numbers of new alleles were registered which are absent in the IPD-IMGT/HLA database. Considerable allelic diversity in Russian population is due to low-incidence alleles. Despite this diversity, the majority of HLA alleles detected at each locus were common. Significant HLA diversity of the donors was connected with a large number of alleles with rare occurrence. The novel alleles identified in our study differed from the known alleles by single nucleotide substitutions. The most common alleles at the four-field level were as follows: A*02:01:01:01 (27.1%), C*07:02:01:03 (13.1%), A*03:01:01:01 (13.0%), B*07:02:01:01 (13.0%), A*01:01:01:01 (11.6%) and C*07:01:01:01/16 (10.4%). The HLA alleles, which are common for Russian populations, are not always common or well-documented alleles in present catalogues. The data obtained in this study may be used as a reference sample for estimation of HLA allele frequencies in Russian population, for proper frequency evaluation of specific alleles when searching donors for allogeneic hematopoietic stem cell transplantation, as well as for association studies between HLA alleles and different diseases, and for research in population genetics.

Purpose. To evaluate the potential option of selecting donor–recipient pairs by using the number of epitopemismatches.Materials and methods. An observational cohort study was carried out, which included 824 adult recipients of ABO compatible deceased donor kidneys. The end point was a transplant loss. If a recipient with a functioning graft died, the observation was censored. The number of epitope mismatches (EpMM) was calculated using open source information on the population frequency of haplotypes and the repertoire of epitopes with confirmed immunogenicity. All possible combinations of the donor and recipient genotypes were compiled, and the probability of each combination was calculated. After that, the number of donor epitopes absent in the recipient was calculated for each combination with a non-zero probability, whereupon the weighted mean EpMM was calculated, where the weight coefficient was the normalized probability of occurrence of each combination.Results. All of the donor – recipient pairs had HLA-mismatches (HLA MM): 1.9% of recipients had 1 HLA MM, 6.7% had 2 HLA MM, 29.9% had 3 HLA MM, 38.5% had 4 HLA MM, 18.1% had 5 HLA MM, and 4.9% had 6 HLA MM. The HLA MM impacted graft survival was determined: log-rank test p < 0.0001, Breslow test p < 0.0001. The median values and the interquartile ranges of EpMM were 6 [4; 7], 12 [7.74; 17.25], 18 [14; 22], 24 [20; 30], 30.5 [25; 37] and 36 [26.5; 44.5] for the cases of 1, 2, 3, 4, 5 and 6 HLA MMs, respectively. An increase in HLA MM resulted in a higher risk of developing donor-specific anti-HLA antibodies (DSA). Hazard ratio (HR) = 1.21 [95% confidence interval (CI): 0.7; 1.9], 1.71 [95% CI: 1.22; 2.36], 2.04 [95% CI: 1.42; 2.73], 2.25 [95% CI: 1.63; 2.96], 2.59 [95% CI: 2.03; 3.29] for 2, 3, 4, 5, and 6 HLA MM, respectively, versus HLA MM = 1. An increase in EpMM also resulted in a higher risk of developing DSA. HR = 1.66 [95% CI: 1.09; 2.47], 2.1 [95% CI: 1.46; 2.91], 2.41 [95% CI: 1.86; 3.03], 2.61 [95% CI: 2.12; 3.12], 2.77 [95% CI: 2.26; 3.33] for 10–19, 20–29, 30–39, 40–49 and > 50 EpMM, respectively, versus EpMM < 10. An increase in HLA MM was associated with an increased risk of transplant loss. HR = 1.24 [95% CI 0.7; 2.15], 1.48 [95% CI 0.86; 2.33], 1.88 [95% CI 1.32; 2.52], 2.41 [95% CI 2; 2.93], 2, 98 [95% CI 2.59; 3.46] at 2, 3, 4, 5, and 6 HLA MM, respectively, versus HLA MM = 1. An increase in EpMM also was associated with an increased risk of transplant loss. HR = 1.71 [95% CI 1.1; 2.49], 2.11 [95% CI 1.59; 2.68], 2.4 [95% CI 1.96; 2.86], 2.59 [95% CI 2.17; 3.04], 2.71 [95% CI 2.31; 3.15] at 10–19, 20–29, 30–39, 40–49 and > 50 EpMM, respectively, versus EpMM < 10. In order to demonstrate the effectiveness of EpMM accounting, we analyzed graft survival among the patients with 4 HLA MM. With the number of EpMM in the range from 10 to 24 and from 25 to 43 the difference in survival rates was statistically significant, but only at the late stages of the post-transplant period: log-rank test p = 0.0067, Breslow test p = 0.0982. The median survival for EpMM 10–24 was 10.33 [95% CI 9.05; 11.61] years, for EpMM 22–43 – 8.67 [95% CI 7.68; 9.66] years, HR 1537 [95% CI 1.114; 2.12]. At the same time, it was not the median of survival that increased, but the proportion of patients with a functioning graft: at 10-24 EpMM after 15 years, 18.28% [95% CI 8.2; 31.67] grafts functioned, while at 25–43 EpMM only 4.75% [95% CI 0.94; 13.64] functioned.Conclusion. In the routine practice of a transplantation center with a short waiting list of its own, it might be possible to improve the kidney transplant survival as a result of considering epitope mismatches, thus reducing the risk of developing donor-specific anti-HLA antibodies and ensuring a higher graft survival rate. This method can be used for additional ranking of transplantation candidates depending on the number of epitope mismatches within the fixed number of HLA-mismatches and thus select the optimal one. Besides, it is theoretically possible to use this method as an alternative to the traditional donor/recipient histocompatibility evaluation. Additional research is required.

Background. Plague is a dangerous natural-focal bacterial disease that can cause emergencies of interstate significance. In 2014–2016, three bubonic plague cases were registered among local residents in the Republic Altai. This circumstance was the reason for implementation of complex preventive measures. Comprehensive studies of the immune status of humans vaccinated (revaccinated) with live plague vaccine are presented in this paper. These people constantly reside and work at the territory of Gorno-Altai high-mountain natural plague focus. Methodology. The study of the clinical material (blood) from 60 volunteers included the determination of the functional activity of phagocytic cells, the production of IFN-γ, IL-4 and TNF-α cytokines, the titre of specific IgG anti-bodies to the capsular antigen of the plague microbe and the concentrations of the main classes of immunoglobulins in blood serum by enzyme immunoassay, as well as immunophenotyping of blood lymphocytes through flow cytometry and the de-termination of the alleles of HLA class II genes by a polymerase chain reaction. Results. The materials of these studies made it possible to determine a number of important parameters indicative of the cellular and humoral immunity activation in humans immunized against plague. Frequently occurring alleles of the HLA-DRB1, HLA-DQB1 and HLA-DQA1 genes were defined. Possible associations of these alleles with the levels of TNF-α and IL-4 production, as well as with the relative content of T-helpers and CD3-CD16+ cells were revealed. Conclusions. The obtained results indicate the immune reconstruction of the humans immunized against the plague. The immunological efficiency and safety of live plague vaccine were confirmed during the exacerbation of the epidemiological situation in active natural plague focus. Nevertheless, further immunological monitoring is necessary to fully characterize the immunological reactivity of the humans vaccinated (revaccinated) with live plague vaccine, and to improve the strategy for specific plague prevention in natural foci.

The study was conducted in 2016 in four stages on the basis of the department of assisted reproductive technologies of the Moscow Regional Perinatal Center of Balashikha with the purpose to determine the tactics allowing increase of the number of patients who managed to successfully overcome the embryonic threshold after the In Vitro Fertilization (IVF) and embryo transfer (ET). Patients were divided in groups with early embryonic losses and the control group. At the following stage of the study determination of the effect of each unfavourable factor on gestation in the first and in the second groups of patients was done. It turned out that such factors as the amount of obtaine oocytes in the course of transvaginal puncture less and equal to 7 (rk = 0,42, р = 0,005); chronic endometritis supported by histological findings (rk = 0,74, р = 0,005); disturbance of the receptor status of endometrium (rk = 0,71, р = 0,005); coincidence with the spouse by HLA system 3 and higher (rk = 0,26, р = 0,03); circulation of AB to β-HCG, weakly positive and positive result of the test by the ELISA method statistically significantly affect the early embryonic losses if the patient refused from the proposed correction before IVF (rk = 0,31, р = 0,005). And on embryonic – innate trombophilias (rk = 0,78, р = 0,00); acquired thrombophilias (rk = 032, р = 0,003); chronic endometritis confirmed by histological findings (rk = 0,64, р = 0,033); circulation failure in the small pelvis by results of the uterine vessel dopplerometry (rk = 0,66, р = 0,00). Comparison of effectiveness of IVF and ET programs in 2016 was conducted in patients who had and didn’t have the risk factors statistically significantly affecting the outcome. The first two groups of patients were subject to specialized therapy depending on the detected unfavourable factors affecting the outcome of the pregnancy after IVF provided that it was possible to correct this factor with subsequent evaluation of effectiveness of repeated attempts of IVF and ET in patients after correction of unfavourable factors as compared to the control group. The tactics of minute detection of patients with statistically significant risk factors of early embryonic and embryonic losses, as well as complex preparation of such patients by modern methods allows increasing the number of patients who managed to safely overcome the embryonic threshold after IVF and ET by 20% and finally to positively affect the take baby home indicator.

Tick-borne encephalitis is a natural focal disease that is widespread in Russia. The purpose of the study was to determine the clinical significance of HLA class II genes in tick-borne encephalitis. Molecular typing of the HLA genes DRB1, DQA1 and DQB1 was performed in 75 patients with tick-borne encephalitis who were hospitalized in the Kirov Infectious Diseases Hospital in 2020-2023, and was carried out using the polymerase chain reaction method with a set of domestic sequence-specific primers (NPF "DNA-Technology", Moscow). The febrile form of tick-borne encephalitis was noted in 41.3% of patients, focal – in 34.7%, meningeal – 16.0%, inapparent – ​​in 8%. For the HLA genes DRB1, the comparison group included 1528 practically healthy individuals of the same population population; for the HLA genes DQA1 and DQB1 – 133 people. The study identified a number of HLA class II genes, which are found significantly more often in patients with TBE compared to the control group (DRB1*1 (c2=12.2; pc

Autoimmune diseases belong to disorders with an unclear etiology. The spectrum of autoimmune diseases is wide, the most well known of them are type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Crohn’s disease, vitiligo, and others. The key role in the development of autoimmune reactions is played by disturbances of immunological homeostasis. Despite numerous researches, the exact mechanisms of autoimmunity still remain unclear. The analysis of data provided by the literature on the mechanisms of disorders of immunological tolerance is presented in the review. The most discussed theories of pathological autoimmune processes development are described: the theory of hereditary predisposition, the theory of immunological dysregulation and regulatory T-cell dysfunction, the theory of network regulation, the infectious theory of autoimmune diseases development (molecular mimicry, polyclonal activation of lymphocytes). The theory of hereditary predisposition reflects the critical role of hereditary factors in the development of autoimmunity, in particular, the data on relations of autoimmune disorders to human major histocompatibility complex are provided. In addition, the data indicating that the development of autoimmune processes in an organism can be associated with changes in the content and function of regulatory T-lymphocytes are provided in the work. These cells are directly involved in the mechanisms of cellular immune responses in autoimmune diseases and may explain the disorders of immunological tolerance, subsequently leading to the development and progression of immunopathology. The idea of idiotype-anti-idiotype interactions, which can serve as a mechanism ensuring normal autoimmune reactions or lead to the activation of autoreactive clones, is revealed in the description of network regulation theory. The infectious theory of development of autoimmune pathologies presented in the review is based on the results of numerous researches and suggests that the viruses can provoke failures of immunity and lead to autoimmunity.

Polymorphisms of gene-candidates of hemostasis disorder (F2:20210 G>A, F5:1691 G>A, F7:10976 G>A, F13:103 G>T, FGB:455 G>A, ITGA2:807 C>T, ITGB3:1565 T>C, PAI-1:675 5G>4G) and frequency of 14 groups of alleles of the HLA-DRB1 locus were study in women, suffered from flu А(H1N1)pdm09 during pregnancy. Significant association between heterozygotes genotype F7: 0976G/A and complicated forms of influenza was found (OR = 1,5). Mutant homozygotes with PAI-1:675 4G/4G genotype also had high risk of severe complicated influenza A(H1N1) (OR = 1,5). Genotypes HLA DRB1*07*15 and DRB1*16*16 were associated with complicated influenza. We assume, that сombined F7:0976GA, PAI-1:6754G4G and HLA DRB1*07*15, *16*16, DRB1*01*01 genotypes may be genetic predictor of severe complicated flu А(H1N1)pdm09 in pregnancy.

Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

Abstract. HLA DRB1* gene associations with idiopathic fetal losses and infertility were studied in women. It was shown that idiopathic fetal losses are associated with HLA DRB1*04 specificity, whereas infertility correlated with HLA DRB1*04/07 genotype. The associations revealed may indicate to a special role of autoimmune events in women during pregnancy. The authors suggest a hypothesis on existence of several immune modes of reproductive losses. HLA genotyping may be applied as a basic technique for their determination.

Abstract. The aim of this work was to reveal novel criteria for prediction of clinical course in myasthenia, based on immunogenetic characteristics of the patients. Sixty-five patients with different clinical forms, various clinical course and severity of myasthenia were involved into the study. All the patients were subject to complete clinical and neurological examination, and all of them have undergone thymectomy, a histology of thymus has been performed. Immunogenetic studies included HLA class I typing (A and B loci), like as HLA class II typing (DRB* locus). A positive association was found between development of disorder and presence of HLAB8 antigen, HLA-DRB1*03, and their combination, thus allowing for suggesting these specificities as probable markers of genetic predisposition for myasthenia development. An HLA-B7 specificity may have a protective role in evolution of this disease. It was shown that clinical severity in myasthenia and degree of neuromuscular conductive disturbances were more expressed in the patients carrying HLA-B8 antigen and HLA-DRB1*03 allele. Evaluation of immunogenetic state at earlier stages of disorder allows of timely differential diagnostics and individual prediction of clinical variability in myasthenia patients.

Subjective estimation of intensity and attractivity of the odor of sweat collected in axillary pits on filter paper is investigatedat 155 young males and 128 young females who were both donors and recipients of odor samples. The role of odor signals in humans’ nonverbal communications is detected. The implactof various factors, bound to psychophysiological and immuno-endocrine characteristics of odor signals donors and recipients, their genetic characteristics, and the state of their health, including sexually-transmitted infections and psychoemotional stress,on the variability ofthe subjective estimation of people’s odors attractivity is investigated. After studying the relations between odor attractivity and HLA genotypes of of donors and recipients, the impact of that genetical factor on selecting of dating pairs in a population is analyzed.

Aims. To estimate significance of HLA II DRB1 and DRB2 allele variants for development of type 1 diabetes mellitus (T1DM) in Bashkortostanpopulation (ethnical Russians, Tatar, Bashkir). Materials and methods. We analyzed DNA of 323 patients with T1DM and 683 healthy controls. DNA was derived from venous bloodsamples by phenol-chloroform extraction. DRB1 and DQB1 gene typing was performed by PCR method. Amplification products wereidentified with electrophoresis on a 1% agarose gel. Statistica for Windows v6.0 and MS Excel 98 software were applied for statisticalprocessing of acquired data. Results. Common markers of high risk for T1DM were found to be DRB1*04, DRB1*17, genotype DRB1*04/*17. On the contrary,lower risk was associated with DRB1*15 allele. In ethnical Russians lower risk of T1DM is also determined by DRB1*11 allele andDRB1*01 in Tatars. Predisposition by DQB1-alleles in Russians and Bashkir realizes only within DRB1*04/*17 genotype. However,in Tatar subpopulation DQB1*0302 is an independent risk marker of T1DM development. Conclusion. Common low risk markers for all three ethnic groups are DQB1*0301, DQB1*0602-08 alleles. Their presence negates riskof disease in all studied subpopulations even within DRB1*04/*17-genotype.

We have studied incidenceof immunological markers of celiac disease in children with diabetes mellitus type 1 (DM1) and their correlation with clinical peculiarities and polymorphous alleles of HLA. It was shown that incidence of celiac markers is higher in DM1 children than in general population and makes up 7.4%. Patients who were seropositive with celiac antigens had gastrointestinal symptoms and iron deficiency more often. The occurrence rate of other autoimmune disorders in seropositive patients was 24%, with high count of autoantibodies towards transglutaminase (AbTT) — 50%. More than 78% of seroposetive patients possessed haplotypes DQ2 and|or DQ8 HLA. The occurrence rate was identical. In patients with high AbTT occurrence of HLA genotypes with DQ2 and/or DQ8 rose up to 100%.

During the screening typing of recruited volunteers with Volga Federal District for unrelated hematopoietic stem cell registry on the loci (HLA)-A, B, DRB1, DRB345 in sample No 1758 identified a new allele at locus A. The use of basic kit AlleleSEQR HLA-A Sequencing in combination with HARP – A2F98A allowed to determine the genotype of this sample – А*30:01:01, a new allele А*25, В*13, 44, DRB1*03, 09, DRB3*02, DRB4*01.

HLA molecules appear to be the principal target of immune allorecognition. The efficiency of transplant directly depends on coincidence of the data obtained by different HLA laboratories. This study discusses the results produced by 12 tissue typing labs in the framework of the initiative program for tissue typing quality control in 2009.