Activation of immune system’s cells is accompanied by metabolic reprogramming, i.e. profound rearrangement of cellular metabolism aimed at fulfillment of increased demands for energy and building blocks for the synthesis of proteins, lipids and nucleic acids. One of the most important metabolic pathways in the cell is glycolysis. In this review, we present data about the role of glycolysis and particular glycolytic enzymes in innate and adaptive immune response. We also consider the possibility to modulate immune response by altering metabolism of cells of the immune system, in particular glycolysis.

Introduction. Psoriasis (PS) is a chronic multifactorial auto-inflammatory skin disease characterized by hyperproliferation of epidermal cells and impaired differentiation of keratinocytes. In recent years more attention has been paid to the role of innate immunity in the pathogenesis of psoriasis and its genetic regulation.

Aim - to study the expression of genes of innate immunity receptors TLR7, TLR9, components of the NLRP1, NLRP3, ASC, CASP1, CASP5 and genes of interleukin(IL)-1β and IL-18.

Material and methods. Totally 32 participants were included in the study. The main group consisted of 21 patients with severe and moderate psoriasis. Patients in the main group underwent a biopsy of healthy and psoriatic skin. 11 healthy donors formed the comparison group. RNA was isolated from the obtained skin biopsies and gene expression was determined by real-time PCR. The expression of target genes was normalized to the housekeeping gene coding β-actin.

Results. It was shown a statistically significant increase in the expression of innate immunity genes in keratinocytes of patients with psoriasis. The expression of TLR9 was higher in both the psoriatic and unaffected skin by 4.8 and 4.3 times, respectively, compared to the control group. At the same time, overexpression of the NLRP1 was detected: 5 times more in affected skin and 3.4 times more in unaffected skin in comparison with healthy donors. CASP5 is a component of the NLRP1 inflammasome complex which provides pro-IL1 and pro-IL-18 processing. Our study showed a significant increase in the expression of the CASP5 gene in the cells of the affected and unaffected skin vs group of comparison by 200 and 194 times, respectively. Activation of CASP5 provides maturation of the active forms of pro-IL1p and pro-IL 18 which increased expression was also revealed in the work.

Discussion. An increase in the expression of TLR7 and TLR9 genes in skin cells of psoriatic patients confirms the significance of the role of these receptors in the pathogenesis of psoriasis. The main function of TLR7 and TLR9 is recognizing endogenous danger signals, in particular auto-RNA and auto-DNA, which are actively released from destroyed keratinocytes in psoriatic inflammation. Activation of TLR7 and TLR9 can stimulate increased expression of the NLRP1 and NLRP3 inflammasome complexes. The revealed predominant overexpression of NLRP1 inflammasome genes indicates that it may play a greater role in the development of psoriasis than the NLRP3 complex. After NLRP1 activation it binds the CASP1 and CASP5 molecules, which genes’ significantly increased expression was demonstrated. At the same time, it is necessary to note the increase of the expression of target genes in both healthy and affected skin of patients with psoriasis, which indicates a systematic change of the innate immunity in the psoriatic process.

Conclusion. The obtained data can be used for a more detailed study of specific signaling pathways of activation of inflammasome complexes and cytokines participation in the development of the psoriatic process and also become the basis for early diagnosis of psoriasis.

Introduction. The main indicator of the quality of a preparation in the creation vaccines based on recombinant proteins is specific activity or immunogenicity. The severity of the protective effect is influenced by the content of antigen and adjuvant in the preparation. An important step in the development of production technology is the selection of the optimal ratio of components. The effect of the ratio of protein and aluminum hydroxide is assessed by the protective properties and by the level of expression of genes for innate immunity sensors and antimicrobial peptide.

Aim of the study - to investigate the effect of the ratio of protein and aluminum hydroxide on the manifestation of protective properties and the level of activity of innate immunity, assessed by the expression of genes for sensory receptors TLR4, NLRC4 and antimicrobial peptide BD2.

Material and methods. The evaluation of immunogenicity was carried out on a mouse model with two-fold immunization with a two-week interval and subsequent infection with a live virulent P. aeruginosa culture. Gene expression was assessed by real-time PCR.

Results. The assessment of the protective properties of the recombinant fusion protein OprF-aTox-OprI in ratios with the sorbent 1 : 1, 1 : 2 and 1 : 3 was carried out, the effect of immunization on the expression of Defb2, Tlr4, Nlrc4, Asc and Caspl genes by murine macrophages was revealed. During the research the protective properties of a recombinant protein with different protein-sorbent ratios (1 : 1, 1 : 2, and 1 : 3), the maximum protective effect was observed when mice were immunized with a preparation with a 1 : 1 ratio. The injecting of the vaccine affected the expression of proteins TLR4, BD2, NLRC4, ASC and CASP1 by macrophages and differed in the severity of the response of the innate immune system depending on the formulation of the preparation used.

Conclusion. As a result of the work performed, the optimal ratio of the fusion recombinant protein OprF-aTox-OprI with the sorbent was determined, corresponding to a value of 1 : 1 and confirmed by the results of immunological studies.

Introduction. Acne is a multifactorial disease, in the pathogenesis of which the leading role belongs to the inflammatory reaction, which develops at all stages of the disease, sometimes even subclinically. It has been established that Cutibacterium acne (C. acne) activates the innate immune system component TLR2 both in the early and late stages of the course of acne. TLR induction causes the expression of immune response genes that encode cytokines and chemokines that induce chemotaxis of cells of the immune system. It has been shown that among the non-receptor tyrosine kinases, Janus kinases (JAKs) have been described, which provide phosphorylation of transcription factors - STAT (signal transducer and activator of transcription) of the JAK-STAT signaling pathway. It has been established that the chains of type I and II cytokine receptors are interconnected with the signaling pathway JAK-STAT, which regulates the action of more than 50 cytokines, interferons (IFN), and growth factors.

The aim of this study was to determine and analyze the difference in the frequencies of SNP polymorphisms of the JAK genes family (JAK1, JAK2, JAK3, and TYK2) in Russian patients with severe acne.

Material and methods. We observed 70 patients (42 men and 28 women) aged 15 to 46 years (median - 22.1 years). The main group included 50 patients (29 men and 21 women) with severe acne. The group of comparison consisted of 20 conditionally healthy individuals (13 men and 7 women). Molecular genetic diagnostics was carried out in all study participants by the high-throughput DNA sequencing - next-generation sequencing (NGS).

Results. Analysis of the genetic defects identified in our study showed that severe acne is associated with 16 polymorphic loci of the JAK1 gene (5 SNPs in exons, 11 SNPs in introns), 22 SNPs in the JAK2 gene (3 SNPs in exons, 16 SNPs in introns, 1 SNP in 3'UTR and 2 SNPs in 5'UTR), 19 SNPs of the JAK3 gene (4 SNPs in exons, 12 SNPs in introns, 2 SNPs in the 3'UTR and 1 SNP in the 5'UTR), and 26 SNPs in the TYK2 gene (7 SNPs in exons, 17 SNPs in introns, 1 SNP in the 5'UTR region, and 1 SNP in upstream).

Conclusion. The obtained results indicate the probable activation of the JAK genes family (JAK1, JAK2, JAK3, and TYK2), which causes excessive activity of cytotoxic cells, stimulates apoptosis and increased secretion of interferons, which inhibit the differentiation and activity of all immune effectors. This, apparently, leads to a slowdown in the activity of the immune response and to a prolonged course of acne.

Introduction. Primary immunodeficiencies (PID) - is a group of genetic disorders with impaired mechanisms of immune function. The only available curative option for the predominance of PID is hematopoietic stem cell transplantation (HSCT). One of the major components of HSCT success is its planning.

Aim of the study - analysis of the results of HSCT planning optimization using medical information system (MIS) «Planning of hematopoietic stem cell transplantation» in children with PID.

Material and methods. To optimize HSCT planning, MIS«Planning of hematopoietic stem cell transplantation» was developed in Dmitry Rogachev National Center for Pediatric Hematology, Oncology and Immunology. From 2012 to October 2020 in our center 302 patients with PID underwent 345 allogeneic HSCT. HSCT outcomes were estimated in 219 patients, who received first HSCT from 2012 to 2019 with TCRap/CD19 graft depletion from either HLA-matched unrelated donors (MUD) (n = 128) or HLA-mismatched related (haploidentical) donors (n = 97).

Results. Transplant outcomes were estimated in 4 major groups of PID: severe combined immunodeficiencies (SCID), n = 33; other combined PID (CID), n = 82; PID with immune dysregu-lation (IDR), n = 43; and congenital defects of phagocytes (DP), n = 30. The time from indication formation to HSCT was significantly lower in SCID group when haploidentical donors were used (p < 0.0001), and in IDR group in comparison to CID and DP groups when MUDs were used (p = 0.003-0.035). Overall survival was similar in IDR - 0.88, CID - 0.8, and DP - 0.82 (p = 0.36-0.83), but was only 0.44 in SCID (p < 0.0001). The mean number of PID patients awaiting HSCT has raised from 27 in 2012-2016 to 98 in 2017-2019. However, time from indication formation to HSCT has not changed, which is likely related to increased number of HSCTs performed: in 2012-2016 it was 37 per year and in 2017-2019 - 51 per year.

Conclusion. Designed MIS «Planning of hematopoietic stem cell transplantation» helps effective HSCT planning, however limited HSCT beds remain an important issue.

Introduction. Pharmaceutical industry widely uses beekeeping products to obtain medicines. Among beekeeping products for medical use, bee venom represents number three on its importance. Pharmaceuticals based on bee venom are used externally, or as injections, or for oral administration. In the production of medicines containing bee venom, it is important to take into account the dose and possible individual response of the human body. The chemical composition of raw bee venom is very complex. Currently, there is no modern normative documentation for standardization of bee venom as a raw material for pharmaceutical preparations. Hence, quality control and standardization of the substance of bee venom intended for the production of medicines represent the urgent need.

Aim of research is to study the physicochemical characteristics of raw bee venom of various batches in order to evaluate and standardize its quality.

Material and methods. We have studied 5 batches of raw bee venom from the same manufacturer. The analysis was carried out on the basis of GOST 30426-97 Methods of purification and standardization of purified bee venom were developed in this study. Those included gel chromatography and PAAG electrophoresis.

Results. According to the results of studies of raw bee venom, 4 batches of 5 did not correspond the requirements of the GOST 30426-97 in terms of mass fraction of water-insoluble impurities (6.01 %); mass fraction of water (9.17 %); hemolysis time (300 s), mass fraction of melittin and apamin (35 %; 0.6 %), respectively. Methods for the purification and standardization of preparations from raw bee venom were suggested.

Conclusion. In our study, we have proven the low level of the standardization of raw poison. The lack of approved normative documents leads to the fact that different pharmaceutical companies use different methods for evaluating the quality of raw materials and methods for their purification, which, in turn, affects the quality of final pharmaceutical products. Therefore the part of General Pharmacopoeia «Raw Bee Poison» (related to standardization of raw materials from which pharmaceuticals are being obtained) should be developed.

The high incidence of allergic rhinitis and the association of allergic rhinitis with an increased risk of other allergic diseases, as well as the limited effectiveness of treatment methods make it extremely relevant to study the molecular mechanisms of allergic inflammation of the nasal mucosa. After the discovery of the IL-33 molecule a number of scientific papers about the role of IL-33 in the allergic inflammatory response and etiopathogenesis of various diseases were published. To date, research of IL-33 role in bronchial asthma pathogenesis has made significant progress, including the development of monoclonal antibodies against IL-33 for the treatment and control of the disease. Similar progress can be expected in the near future in studies of IL-33 in the pathogenesis of allergic rhinitis. The particular interest of modern allergology research lies in the field of the relationship between the production of IL-33 and pathomorphological changes in the nasal mucosa. Despite the limited number of publications devoted to this issue, literature analysis suggests that interleukin-33 significantly affects changes in the nasal mucosa and mediates clinical manifestations of allergic rhinitis.