Fundamental studies in neuroimmunophysiology are the keystone for development of new therapeutic approaches to the treatment of infectious, allergic, oncologic and autoimmune diseases. The achievements in this field allowed approving new treatment methods based on irritation of afferent and efferent fibers of autonomic nerves. That became possible due to numerous studies of pathways between the immune and nervous systems performed over last two decades. The milestones in the history of neuroimmune communication research are represented here. The immune system organs – bone marrow, thymus and spleen are coupled to central nervous system (CNS) via sympathetic nerves. Information about LPS and bacteria emergence in peritoneum, intestine and parenchymal organs reaches the brain via parasympathetic pathways. After vagotomy, the brain neurons do not respond to this kind of antigens. The pattern of brain responses to different applied antigens (the EEG changes and the quantity of c-Fos-positive neurons) is specific for definite antigen, like as algorithms of electroneurogram after exposure to different cytokines. Activation of parasympathetic nerves causes the inhibition of inflammation. The entry of any antigens into the body initiates production of cytokines (IL-1, TNFα, IL-6, IFNγ etc.), via specific receptors which are present on peripheral neurons and terminals of vagus nerve, i.e. the vagal afferent terminals and neurons respond to cytokine action, and these signals are transmitted to CNS neurons. The afferent vagal fibers end on the dorsal vagal complex neurons in the caudal part of medulla oblongata. The information about bacterial antigens, LPS and inflammation is transmitted to the brain via afferent autonomic neural pathways. The speed of this process is high and significantly depends on the rates of cytokine production that are transmitters of signals upon the antigen exposure. It is important to emphasize that this events occur within minutes, and the response to the received information proceeds by reflex mechanisms, i.e., within fraction of a second, as exemplified by inflammation (“inflammation reflex”). This is a fundamentally new and revolutionary discovery in the functional studies of immune system regulation. Clinical efficiency of n. vagus stimulation by pulsed ultrasound was shown, being used for the treatment of inflammatory, allergic and autoimmune diseases, e.g., multiple sclerosis, rheumatoid arthritis, renal inflammatory diseases. Electrical stimulation of the vagus nerve reduces the death of animals in septic shock by 80%. The mentioned data have made a revolution in understanding the functional arrangement of immune system in the body. A hypothesis is represented, which suggests how the information on the antigen exposure is transmitted to the brain.

Aging is one of the most complex biological phenomena that affects all human physiological systems, including the immune system. Immunosenescence is understood as structural and functional changes in both adaptive and innate immunity systems. The so-called inflammaging is among manifestations of immune aging. It is an age-related increase in inflammatory mediators and development of an inflammatory phenotype. An important role in development of inflammaging is assigned to chronic stimulation of immune system by exogenous and endogenous danger signals (pathogen-associated molecular pattern, PAMP and damage-associated molecular pattern, DAMP), which include viruses, microbiota of the gastrointestinal tract, free radicals, etc. PAMP and DAMP are recognized by the innate immunity system cells through the pattern recognition receptors (PRR), e.g., Toll-like receptors (TLR), RIG-I-like receptors (RLR), NODlike receptors (NLR), lectin receptors. Stimulation of PRR leads to activation of intracellular signaling and increased expression of pro-inflammatory factors. PAMPs are the most powerful activators of PRR and inflammation triggers; DAMPs can activate the same receptors and signaling pathways, causing the development of a sterile inflammatory response. The NF-kB signaling pathway is considered as a key signaling pathway for inflammaging. NLR stimulation also leads to formation of inflammasome. Its function is to transform the pro-inflammatory cytokines to a biologically active form, which is an important for the formation of a pro-inflammatory phenotype and development of inflammaging. This process is considered an important risk factor for morbidity and mortality among older people. Chronic inflammation underlies pathogenesis of many age-related diseases, such as osteoporosis, atherosclerosis, Alzheimer’s disease, Parkinson’s disease, type 2 diabetes. Various chronic diseases associated with age are directly related to PAMP and DAMP-induced TLR or NLRP3-mediated inflammatory response. Hence, these ligands and their receptors can be suggested as biomarkers and interventional targets for age-related disorders. Despite numerous studies in age-associated pathology, there are only few works on the contribution of innate immunity in healthy aging. It remains unclear whether the inflammatory phenotype is a manifestation of healthy aging, or it is associated with development of age-related pathology. Further study of the mechanisms of inflammatory aging will reveal biomarkers of healthy aging and potential targets for the treatment of age-associated diseases.

Low-affinity Fcγ-receptors that recognize the Fc portion of immunoglobulin (Ig) molecules, usually being in antigen-bound state, thus representing a link between innate and adaptive immunity. They play a significant role in inflammatory and infectious diseases. Among them, a separate FcγRII family (CD32) is discerned, which is characterized by transmission of intracellular signal independently of the common γ-chain, they have one α-chain containing two extracellular immunoglobulin-like domains. FcγRII receptors are present in almost all cells of the innate immune system: monocytes and macrophages, neutrophils, eosinophils, dendritic cells, as well as on B-lymphocytes and platelets. They perform two main functions: target recognition, facilitation of phagocytosis and destruction of antibody-opsonized cells by monocytes/ macrophages (including pathogenic cells). In parallel, the phagocytes are activated via the cytokine synthesis stimulation. The FcγRIIA (CD32a) and FcγRIIC (CD32c) activating receptors, like as FcγRIIB (CD32b) inhibiting receptors are present among the members of the FcγRII family. The low-affinity FcγRII receptors bind to IgG, with immune complexes being their natural ligands. High levels of immune complexes are usually found in both chronic viral infections and autoimmune diseases. There are shown polymorphic variants of the CD32a gene, which can affect the receptor function, and, thereby, causing susceptibility for different infections, influence the development of autoimmune diseases and primary immunodeficiencies. Activation of the CD32a receptor induces the production of pro-inflammatory cytokines, including TNFα and interferons, that are involved into inflammation in systemic lupus erythematosus, Kawasaki disease, Graves’ disease and rheumatoid arthritis. It has been shown that antibacterial activity of platelets is carried out via the CD32a receptor. The study of CD32a expression in people The CD32a receptor is considered a biomarker of cells that are a reservoir of HIV infection. At the present time, however, many questions remain regarding the mechanisms of CD32a expression of on HIV-infected cells and the role of CD32a in the formation of an HIV reservoir and/or development of appropriate resistance. In addition to HIV infection, the significance of FcγR receptors is shown in other infectious diseases, for example, with influenza and dengue virus infections. Better understanding of the CD32a structure and function will help to assess its role in immunopathogenesis of different conditions. This review focuses on the role of CD32a in development of the normal immune response in normal state and various diseases.

This review article presents the literature data supporting an idea on the role of serine proteases, and, especially, cathepsin G (CG), in pathogenesis of chronic obstructive pulmonary disease (COPD). Most studies show that the imbalance in protease-antiprotease systems in COPD is one of the main factors in the disease progression and deterioration of patient’s prognosis. CG seems to act simultaneously in several main pathogenetic aspects of the disease: it stimulates inflammation in the bronchial mucous membranes, leads to remodeling of elastic framework of the lungs, causes degradation of the phospholipid transfer protein (PLTP). A study by Gudmann et al. (2018) reported on quantitative assays of elastin fragments, which are formed under the action of CG (EL-CG) and significantly increased in COPD, thus proving the effects of CG on destruction of elastic framework in lungs. In a recent study, Rønnow S.R. et al. have recommended the assays of EL-CG fragments, reflecting elastin CG remodeling, for use as a prognostic biomarker for overall mortality in COPD. The effect of CG on PLTP was studied in the works of Brehm A. et al. It is known that the anti-inflammatory effect of PLTP is mediated by macrophages, via the ATP-binding cassette transporter (ABCA1), blocking the nuclear factor light chain enhancer (NF-kB) and reducing secretion of pro-inflammatory mediators by these cells, including (TNFα). The CG inhibition in bronchoalveolar lavage fluid (BALF) of the patients with COPD consistently disrupts its ability to cleave recombinant PLTP (rPLTP). At the same time, the highest CG activity was registered in BALF from smokers and in patients with COPD. Negative correlations between CG activity and PLTP level were detected. With respect to above, one may expect an increased interest for developing the inhibitors of serine proteases, including CG. E.g., the sunflower trypsin-1 inhibitor (SFTI-1) is a potent CG inhibitor, showing a significant increase of its activity when the P1 residue is replaced from Arg5 to Phe5. According to most researchers, powerful and selective CG inhibitors may be developed in future on the basis of SFTI-1, thus requiring further in-depth research.

Psoriasis is a chronic auto-inflammatory, genetically determined dermatosis, being multifactorial by origin, characterized by hyperproliferation of epidermis, affected keratinocyte differentiation and inflammatory reaction in dermis. The disease is characterized by a tendency to spread over the area of lesion, and involvement of articular tissue in the pathological process, which significantly affects the living standards of patients and causes their disability. There are many provoking factors that contribute to occurrence of psoriasis, or progression of existing psoriatic process in individuals with a genetic predisposition. These factors include adverse climatic conditions, skin trauma, exposure to ultraviolet light, burns, infections, etc.

This review describes the role of innate immunity in pathogenesis of psoriasis, and describes in detail the mechanisms involved into induction of inflammation of PAMPs and DAMPs. In psoriasis, positively charged catelicidin is considered one of the most important DAMPs, which can form a complex with negatively charged cell polyanions-LL-37/auto-RNA and LL-37/auto-DNA. The interaction of PAMP/DAMP ligands with specific PRR receptors leads to signal activation of effector components of immune system, i.e., assembly of inflammasome complex, caspase activation, synthesis of inflammatory cytokines and processing of their immature forms. The review focuses on the role of TLRs under the conditions of physiological norm, which recognize danger signals and provide protection from pathogens and their timely elimination, and in development of pathological process. Activation of TLRs induces the production of pro-inflammatory cytokines, interferons and antimicrobial peptides, chemokines that support the development of psoriatic inflammation.

In addition to TLRs, the mechanisms of involvement of inflammasomes in the development of psoriasis, which provides processing of mature forms of IL-1β and IL-18, are described in detail. Mature forms of these cytokines mediate the development of inflammation in psoriatic focus. In addition, processing of these cytokines by caspases using the positive feedback mechanism provides an additional signal to activate transcriptional activity of their genes and contributes to perpetuated inflammation.

The review presents data confirming participation of inflammasomes in the pathogenesis of psoriasis. Much attention is paid to description of pharmacological inhibitors of inflammasomes, which in the future may be the drugs of choice for treatment of inflammatory diseases. The study of molecular mechanisms of the innate immune system will reveal new approaches to prognosis and development of targeted therapy for psoriasis.

Based on the III International Consensus on the definition of Sepsis and Septic Shock (Sepsis-3), the modern definition of septic shock was proposed: “Septic shock is a type of sepsis that is accompanied by severe hemodynamic, metabolic and cellular disorders, and these disorders are associated with a higher risk fatal outcome”. Despite the classic idea of septic shock development (proinflammatory, immunosuppressive phases and, finally, multiple organ failure with distinct shock organs), the theory of activation of the caspase, endocannabioid system and system of protein of programmed death-1 in evolving septic shock are promising approaches to development of new diagnostic and therapeutic methods. Lymphopenia is already observed at an early stage of septic shock, which further leads to deep immunosuppression. Previous experimental studies have revealed some treatment methods to reduce the pro-inflammatory stage, which, however, did not show desired results in clinics. Now it is necessary to look for ways to inhibit apoptosis, depletion of lymphocytes, macrophages and other immune cells in the course of septic shock. It is known that caspases mediate innate detection of pathogenic microorganisms, cause pyroptosis, activation of monocytes. It has been proven that inhibition of caspase-8, caspase-11 leads to decreased monocyte functioning and cytokine release, which plays an important role in immunopathogenesis of septic shock. Associations of PD-1 and PD-2 expression on CD4+  lymphocytes and monocytes are also shown to be connected with immune dysfunctions, decrease in lymphocyte proliferation, and increased interleukin-10 concentration. Stimulation of the cannabinoid receptors is able to reduce inflammation by inhibiting cytopathic and immunosuppressive effects of pathogens. It has been shown that classic septic shock biomarkers (pro-inflammatory, anti-inflammatory cytokines; procalcitonin, lactate, etc.) do not have predictive power in relation to the outcome of the disease. Circulating and citrullated histones, determined by mass spectrometry, may serve as potential diagnostic markers of septic shock, but they require further study. Use of oxidized phospholipid oxPAPC (Oxidized 1-palmitoyl-2-arachidonoyl-snglycero-3-phosphocholine), hydrogen sulfide and Fasciola hepatica fatty acid binding proteins (hepatic fluke) prevents oxidative stress, synthesis of pro-inflammatory cytokines and provides maturation of macrophages and dendritic cells. Further study of immunological reactions during septic shock is of great importance for substantiation of new approaches to the diagnostics and therapy of septic shock.

The aim of this study was to generate dendritic cells from the bone marrow of mice (DC) in vitro and to assess the effect of virulent and attenuated variants of influenza virus on the maturation of DCs. Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) were used in combination, to induce differentiation of mouse bone marrow (BM) mononucleocytes into DCs. On the 5^th day, distinct variants of influenza virus were added to the cell culture, and the cells were additionally incubated for 2 days. The morphological characteristics of DCs, immunophenotype of DCs and expression of some Toll-like receptors were evaluated. On the 5^th day of incubation. the DCs acquired typical morphological characteristics. DCs were large in size with an eccentrically located nucleous, often irregular in shape, with numerous processes. On the 7^th day of incubation with influenza virus variants, their cytoplasm was somewhat denser. DCs acquired more processes, necessary for intercellular contacts. Expression levels of CD11c, a specific marker of BM-derived DCs, and of co-stimulatory molecules such as CD40, CD80, CD86, and MHC-II were elevated in mature DCs. Virulent versus attenuated strains of the influenza virus induced special variants of DCs differentiation, with respect to expression rates of differentiation markers, as well as expression of Toll-like receptors and costimulatory molecules. Conclusions. The in vitro cultured murine mononucleocytes derived from bone marrow can produce a large number of n-DCs, that can mature in the presence of different variants.

During evolution of the DC immunophenotype treated with variant influenza viruses, we have found distinct signs of immunosuppression.

The attenuated U-2 and M-26 influenza variants obtained by site-specific mutagenesis upon development of DCs immunophenotype, exhibited a decreased immunosuppressive activity and were not inferior to the cold-adapted (CA) reassortant for the most positions, but exceeded it in some instances. These studies can help to assess the criteria for evaluation the efficiency of in vitro developed influenza vaccines.

Crohn’s disease is an urgent problem of modern gastroenterology due to increasing prevalence, severity of complications and side effects of the basic therapy, in particular upon treatment with 5-aminosalicylic acid (5-ASA). Searching, development and trials of new effective drugs with minimal side effects in Crohn’s disease is an urgent task. Curcuma longa is one of the initial substances containing curcumin with antioxidant, cytoprotective, anti-inflammatory properties. Its effectiveness has been demonstrated in few studies with its systemic use in Crohn’s disease treatment. Our aim was to perform a comparative analysis of curcumin and 5-ASA effect applied as a composition of rectal suppositories, studying clinical signs and indices of immune status in experimental Crohn’s disease. The study was performed on 70 Wistar male rats. Crohn’s disease was modeled by introduction of a 50% alcohol solution of trinitrobenzene sulfonic acid (TNBS) per rectum, and verified by clinical and morphological methods. Rectal suppositories, each containing 50 mg of 5-ASA and original suppositories containing 0.075 mg of curcumin were used over 12 hours during 7 days. The studies were performed on the 3^rd , 5^th and 7^th days of Crohn’s disease.

In the course of experimental TNBS-induced Crohn’s disease in animals, an increased frequency of bowel motility, appearance of blood in the stool, decreased body weight progressed from the 3^rd to the 7^th days of observation, along with increased number in CD3⁺, CD45RA⁺ lymphocytes in blood, higher number of segmented neutrophils, lower absorption and NBT-reducing activity of blood neutrophils, increased serum concentrations of IL-23, IgM, IgG. Composition of the new medication form was justified; production technology and standardization of the suppositories containing curcumin for the treatment for Crohn’s disease were developed. Usage of rectal suppositories with curcumin is associated with decreased severity of clinical signs, decrease and partial restoration of segmented neutrophils, CD3⁺ lymphocyte numbers in blood, recovery of absorption and NBT-reducing ability of blood neutrophils, and decrease of IL-23, IgM, IgG concentrations in serum. The effectiveness of rectal suppositories with curcumin is compared to the effectiveness of the use of rectal suppositories with 5-ASA in terms of disease activity index, the number of neutrophils and CD3⁺ lymphocytes in the blood, serum concentrations of IL-23, IgM and IgG, in, at lesser extent, in terms of absorption and NBT- reducing ability of blood neutrophils.

The composition and production technology of rectal suppositories with curcuminwas developed; the leukocyte populations, CD3⁺, CD45RA⁺ lymphocytesin blood were assesed, neutrophil absorption and NBT-reducing ability, IL-23, IgM and IgG concentrations were determined; the use of rectal suppositories with curcumin in experimental Crohn’s disease is comparable with the effectiveness of rectal suppositories with 5-ASA.

Among the reasons of primary lymphedema development, a certain role belongs to genetic factors. The specific molecular products participate in remodeling of blood and lymphatic vascular networks. Vascular endothelial growth factors (VEGFs) are key regulators of endothelial functions of the cells, which are responsible for lympho- and vasculogenesis. Moreover, matrix metalloproteinases (ММР) may act as regulators of both lymphangiogenesis, and angiogenesis. Since the regulatory regions of VEGFA gene, as well as of ММР genes are polymorphic, one may suggest, that their different expression level, determined by these polymorphisms, could be associated with development of swellings typical for lymphedema.

We have analyzed gene polymorphisms in two regulatory regions of vascular endothelial growth factor-A VEGF-A (rs 699947 and rs 3025039), and matrix metalloproteinase genes MMP2 (rs 2438650), MMP3 (rs 3025058), MMP9 (rs 3918242), and their combinations in the patients with primary lymphedema.

A group of patients with primary lymphedema included 72 subjects (55 women and 17 men) at the age of 18 to 81 years. Control group included 526 inhabitants of Novosibirsk (153 men, 373 women) without chronic diseases, comparable for age with lymphedema patients. We have performed typing of regulatory regions in VEGF (rs 699947, rs 3025039), ММР2 (rs 2438650), ММР3 (rs 3025058), ММР9 genes (rs 3918242). Fifteen complex genotypes have been revealed that were positively associated with disease. Analysis of the gene network topology has outlined the main intergenic interactions upon primary lymphedema development. MMP2 -1306 CC, MMP9 -1562CC and VEGF +936CC arrange the basic knots in the gene network (53% of total interactions). A number of significantly different complex genotypes was revealed at patients with primary lymphedema with normal body mass index (BMI < 25) and obesity (BMI < 30). Hence, frequency of complex genotype VEGF +936 CC: MMP3 -1171 5А6А:MMP9 -1562 CC in the patients with obesity is increased more 5.5-fold compared to the patients with normal BMI.

The data obtained may presume a certain value of the analyzed gene polymorphisms in pathogenesis of primary lymphedema. Topological analysis of gene networks allows to study the structural and functional organization of gene-gene interactions for development of approaches to individyal preventive maintenance and therapy of the disease.

Eight polymorphic loci in the TREM-1 gene (rs1817537, rs3804277, rs6910730, rs7768162, rs2234246, rs4711668, rs9471535 and rs2234237) were genotyped in 131 children with congenital heart defects (CHD) without proven chromosomal anomalies, and 103 conditionally healthy children (control group) matched for age and gender. Genotyping was performed by polymerase chain reaction (PCR) using TaqMan probes. The frequency of these genotypes was checked for Hardy–Weinberg equilibrium using a free tool (http://bioinfo.iconcologia.net/SNPstats). Analysis of inter-locus interactions was performed by Multifactor Dimensionality Reduction method. It was shown that the combination of four loci, i.e., rs1817537, rs3804277, rs2234246 and rs7768162 may determine susceptibility and persistence for CHD without chromosomal diseases. Increased CHD risk is associated with two-locus model rs1817537*G/G – rs3804277*T/T (OR = 8.26) and three-locus model rs2234246*C/T – rs1817537*C/G – rs7768162*A/G (OR = 13.76). The two-locus model rs1817537*С/С – rs3804277*T/T (OR = 0.03) and three-locus model rs2234246*T/T – rs1817537*C/C – rs7768162*G/G (OR = 0.03) were associated with a decreased risk for CHD without detectable chromosomal anomalies.

An early-stage infection induces the most powerful reactions of immune system. 137 clinical histories of patients with HIV infection, and HCV/HIV-infected at the early stages of HIV infection were subjected to analysis. Patients and methods: a group of 45 patients at early terms of HIV infection included 25 cases of HCV/HIV-infected patients (first group), and 20 cases with HIV mono-infection (second group). Duration of infection was less than 1 year (with positive ELISA test), with mean terms of HIV immunoblot positivity of 5.5±0.6 months. For comparative analysis, the natural course group was examined, i.e., 43 patients with combined HCV/HIV infection (third group), and 49, with HIV monoinfection (fourth group) with a duration of HIV infection for 4.4±0.21 years. The group of healthy controls included 52 persons. We aimed to perform a comparative evaluation of clinical course and immunological features from the early stages of infection in the patients with combined HCV/HIV and HIV infection. Results: at early stages of infection, clinical pattern in HCV/HIV-infected patients was dominated by purulent-inflammatory, fungal infections and secondary diseases, along with more pronounced inhibition of cellular immunity and increased viral load of RNA HIV, as compared to data on HIV-infected patients.

Acute myocardial infarction (AMI) is one of the most common cardiovascular complications with a complex pathogenesis where inflammatory markers are involved in disease etiology. The aim of this study was to investigate haptoglobin phenotypes and their association with some risk factors in patients with a history of AMI. 120 patients who were referred to the emergency department of Amir Al Momenin hospital of Zahedan city, Zahedan-Iran were recruited in a cross-sectional case control study. 120 normal individuals were also chosen as controls for this study. Serum was isolated from routine bloods taken for diagnostic tests and used to determine haptoglobin phenotype distribution by electrophoresis. Phenotype differences as percent of phenotype frequency in patient and control groups were analysed using the χ² test and SPSS software. A high frequency of serum Hp2-2 haptoglobin phenotype in patients and healthy control were found (62.5% and 58.3% respectively). A meaningful statistical correlation between high frequency of Hp2-2 haptoglobin phenotype and AMI was not found (p value = 0.484). Whereas high frequency of Hp1-1 and HP2-2 phenotypes was associated with hyperlipidemia and hypertension respectively (p value = 0.01 and 0.04). Our results showed that there was a high frequency of Hp2-2 haptoglobin phenotype in patients as well as healthy controls in the population studies. High frequencies of Hp1-1and Hp2-2 phenotypes were associated with AMI in patients with hyperlipidemia and hypertension respectively. Thus these phenotypes in AMI patients may modulate the inflammatory response in combination with hyperlipidemia and hypertension.

The article presents the results of studying and evaluating the impact of magnetic nanoparticles of ferrihydrite on neutrophil granulocytes in human blood (in vitro) in order to determine their bio compatibility and eco toxicity. The subject soft here search were blood neutrophil granulocytes of 29 conditionally-healthy donors of blood, as well as magnetic nanoparticles of ferrihydrite (NP), the preparation dose in minimum concentration reached 25 mg, in maximum concentration it reached 50 mg per 10⁶ cells/ml. We implemented the sol of magnetic NP, obtained by biogenic synthesis in International Scientific Centre for Studying Extreme States of an Organism. Functional activity of blood neutrophil granulocytes has been determined by luminol-dependent chemiluminescence. Magnetic NP were introduced into pilot samples straight before chemiluminescent analysis, and also after the incubation with in 30 minutes under 37 °С entigrade. As a result of thee stimation of the early response of neutrophil granulocytes to the influence of minimum concentration of magnetic NP in vitro we found statistically true decrease of the intensity (1.6 times), the area under the curve (2.1 times) in zymosan-induced chemiluminescent response, the activation index (2.3 times). When evaluating the late response of neutrophil granulocytes to the influence of maximum concentration of magnetic NP in vitro we have found statistically true lowering of the time of reaching the peak (10 times) of spontaneous chemiluminescence. More over we marked consider able lowering of maximum intensity 6 times and the reduction of the area under the curve of zymosan-induced chemiluminescence 5.6 times under the influence of magnetic NP under the lowering of activation index 3.7 times. The authors determined that magnetic NP were intensively decreasing the functional activity of neutrophil granulocytes. The intensity of the impact is higher under the preliminary incubation of the cells with magnetic NP. At the same time, short effect of magnetic NP to neutrophil granulocytes can be a modulating one and depends on the initial level of cell reactivity. We revealed that magnetic NP influence concerns only activated cells.

Patients with chronic kidney disease (CKD) are a unique clinical “model” for studying the functions of immunocompetent cells under the conditions of severe endogenous intoxication, inflammation and immunosuppression. The aim of our study was to perform a comprehensive assessment of morphological and functional activity of neutrophils in patients at the terminal stage of chronic renal failure. We examined 49 patients (16 women, 33 men, 22 to 63 years old) with CKD 5 D (according to the K/DOQI classification, 2006), and 60 healthy individuals (controls). Leukoconcentrates of venous blood were used as biological samples for the study. The following functional properties of neutrophils were evaluated: the formation of extracellular networks (netosis, NETs) determined microscopically with Romanovsky-Giemsa staining during cell cultivation for 30 and 150 minutes; production of reactive oxygen species (ROS) using cytochemical method with nitro blue tetrazolium, apoptotic activity (luminescence microscopy after staining with a mixture of acridine orange/ethidium bromide), as well as absorption capacity in the reaction of phagocytosis. The tests were performed in spontaneous and stimulated versions. The ATCC 25923 S. aureus strain killed by heating was used as a stimulator. An increase in netosis parameters was revealed in 30-min (but not 150-min) cell cultures in both spontaneous and stimulated versions (p < 0.001), as well as apoptosis (p = 0.02). ROS production by neutrophils and their absorption activity did not significantly change. The parameters of netosis and apoptosis directly correlated with each other (r_s = 0.34; p = 0.03), being also dependent on the level of azotemia (correlation coefficient for the indices of netosis and urea level was: r_s = 0.41; p = 0.01; for apoptosis and urea, r_s = 0.34; p = 0.02). A relationship was found between the level of apoptosis and ROS production by neutrophils (r s = -0.51; p = 0.03). These studies have shown that the cells from patients with terminal-stage CKD are prone for a suicidal program – apoptosis and netosis. Considering the increased netosis just upon shorter cultivation of leukocytes (30 minutes), it can be assumed that NADPH-independent mechanisms are primarily involved. The direct dependence of netosis and apoptosis parameters on the level of azotemia allows us to consider accumulation of endogenous intoxication products, in particular, oxidized proteins, in the patient’s body as one of the primary reasons for increasing the suicidal neutrophil program.

Rheumatoid arthritis (RA) is a systemic disease that causes progressive joint damage and disability. The affected tissues are histologicaly characterized by prominent infiltration with inflammatory mononuclear cells, such as T cells and macrophages, and proliferation of synovial fibroblasts. Inflammatory cytokines, including tumor necrosis factor (TNF), and IL-6, which are mainly produced by macrophages, play a central role in the development of synoviitis. For example, TNF is shown to directly induce synovial fibroblast proliferation, which leads to the pannus formation. TNF is also critical for the expression of inflammatory chemokines and adhesion molecules, which, in combination, facilitate further leukocyte attraction and perpetuation of inflammatory responses. In addition to environmental factors, genetic constitution of host organism seems to play a crucial role in acquiring and development of the disease. The present study was carried out to investigate the association of HLA-class 11 (DR, DQ) with RA disease by genotyping in Iraqi patients, as well as to provide information about genotypes that confer susceptibility or resistance to this disease. Aim of the study was to assess the role, strength and profile of immune response in patients with rheumatoid arthritis by estimation of TNFα, IL-10 and levels, as compared to healthy control group, and to identify a role for certain alleles in occurrence of the disease. The 5-ml samples of venous blood were taken from 30 patients suffering from confirmed rheumatoid arthritis, 19 patients were females and 11 males, as well 30 healthy control samples were enrolled in this study. All the samples were subjected to ELISA test, in order to estimate TNFα, and IL-10 levels in serum from 3 ml of blood. DNA was extracted from 2 ml of blood, and HLA-Class Il genotyping was performed by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSO). A highly statistical significant variation, both in TNFα, and IL-10 levels between RA patients group and healthy control group was observed (p < 0.001). No statically significant differences between males and females in frequency of the RA (p = 0.119). HLA-class II genotyping of RA patients in comparison with healthy control showed significant differences in some alleles between the both groups. Some DR alleles proved to be informative, e.g., the DR*0403 allele showed a significantly increased frequency in control group with 35%, compared with 6.67% in RA group (p = 0.02). The DR*701 allele showed increased frequency in the patients with 9 cases (30%, p = 0.007). Genotyping of DQ alleles did not any no significant differences. Although *0202 allele occurred in 40% of patients group versus 15% in control groups, it was not significant (p > 0.05).

Our work was aimed for studying the role of systemic of IL-23 and IL-20 levels in different clinical variants of sclerotic lichen in women. The study was based on results of clinical data (anamnesis, examination, palpation, vulvoscopy) and immunological studies (determination of IL-20 and IL-23 cytokines in peripheral blood) in the patients with sclerotic lichen (114 patients aged 42.5±15.1 years). Group I included patients with atrophic variant of sclerotic lichen (n = 58); group II, with sclerotic variant of sclerotic lichen (n = 34). Group III included women with a sclero-atrophic variant of this disorder (n = 22). The control group consisted of conditionally healthy women without present, or previously documented vulvar pathology (30 persons). Criteria for inclusion were as follows: women 20 to 60 years old, the presence of a benign vulvar disease, absence of treatment with immunotropic drugs over past year. Exclusion criteria: presence of viral infection (HPV, HSV), detection of STI, presence of acute inflammatory process (including vulvitis and vaginitis), cancer diagnosis, symptoms of autoimmune disorders, pregnancy, and the patient’s reluctance to participate in the study.

Predominant increase of IL-23 was revealed in all clinical groups of the examined patients, the most pronounced increase (2.7 times) was in severe sclerotic lichen (p < 0.0001). IL-23 concentration in the 2nd clinical group corresponded to the reference age-matched values. There was a significant increase in the blood content of IL-20 in subgroup 2.2 of the patients with sclerotic lichen (p < 0.0001), as well as in patients from group 3 with a mixed clinical course of its disorder (p < 0.0001). Meanwhile, the absence of pronounced vulvar tissue sclerosis in sclerotic variant of sclerotic lichen (subgroup 2.1) was accompanied only by a tendency for increased IL-20 concentration (p = 0.502), and only a trend for decrease in atrophic variant of sclerotic lichen (p = 0.288). In general, analysis of these data presumes a significant role of IL-20 and IL-23 in pathogenesis of sclerotic lichen in women. The cytokine assays in various clinical variants of this vulvar disorder may provide additional differential diagnostics (IL-20), and to assess severity of atrophic and sclerotic changes in vulvar tissues (IL-23) in women with sclerotic lichen.

Chronic granulating periodontitis among children has a high prevalence, which determines the relevance of its research, medical and social significance. The exacerbation of the disease is accompanied by various disorders in the immune system and, above all, at the local level. However, changes in local humoral immunity in children with exacerbation of chronic granulating periodontitis (CGP) have not been studied. Impact of modern immunomodulators and, in particular, Derinat, on pathological changes of local parameters of humoral immunity was not analyzed in pediatric patients with this disorder.

The aim of this work is to study local humoral immunity parameters during CGP exacerbation in children and on the background of combined therapy with Derinat, Unidox-Solutab, and Tycveolum (oil extract from pumpkin seeds).

The analysis of immunological disorders in gingival fluid was performed in 93 children aged 12-14 years with exacerbation of chronic granulating periodontitis, who underwent examination and treatment in Belgorod city pediatric dental clinic, and at the Department of Pediatric Dentistry of Belgorod State National Research University in 2013-2015. The patients included in the study were divided into 2 groups: control group (n = 48), receiving conventional treatment, and the main group (n = 45), who, in addition to standard therapy, were treated with Derinat, Unidox-Solutab and Tycveolum. Contents of immunoglobulins in gingival fluid were determined by turbidimetric method using the Microlab-300 photometer. Lysozyme and lactoferrin were studied by solid-phase enzyme immunoassay.

Exacerbation of chronic granulating periodontitis in childhood is associated with a representative decrease of sIgA, IgA, lysozyme and lactoferrin in gingival fluid, and increased levels of IgM and IgG. Upon treatment with innovative therapy, including derinate, as one of the components, in CGP patients, there was a significant improvement of immune parameters on the 14th day of observation. Normalization of all studied parameters of local immunity was noted in the patients of main group by the 30 th day of observation. Meanwhile, only some immunological parameters reached normal reference values in the control group of patients. Conclusion. The identified new mechanisms of Derinat effects upon humoral immunity and it’s effective use during exacerbation of chronic granulomatous periodontitis in children.

Measles vaccination In Russian Federation was introduced in 1967. It was assumed that the twodose vaccination regime would lead to a decrease in the incidence and elimination of measles. A number of studies have shown that up to 10% of individuals who received two doses of measles vaccine do not develop a specific humoral immunity, or do not maintain it at a protective level. This fact may contribute to gradual accumulation of persons susceptible for measles infection in the population, thus leading to emergence of new viral outbreaks in the future. The aim of this study was to perform dynamic monitoring of the post-vaccination measles immunity. The study involved 149 people. All the examined persons were divided into 2 groups. The group of comparison included persons, aged 19 to 51 years, in whom absence of measles immunity was serologically confirmed (n = 76). This group was twice vaccinated with live measles culture vaccine (NPO “Microgen”, Russia). Determination of IgG to measles virus was carried out 1 month after vaccination and revaccination. The control group consisted of persons with documented evidence of double immunization against measles virus, with laboratory-confirmed measles immunity (n = 73), aged 19 to 53 years. The comparative dynamics of development and contents of antibodies in the comparison-control groups were considered, with respect to the WHO age classification. Basic and postvaccinal dynamic determination of IgG to measles virus in serum was performed by ELISA using the “VectoKor-IgG” test system (Vector-Best, Novosibirsk). When analyzing the results of the study, it was noted that the level of measles immunity group in older persons from control group (over 45 years old) was initially higher, than in younger subjects. Among young people, the titers of specific measles antibodies reached the values of the control group of the corresponding age after the first vaccination, whereas the level of specific measles antibodies in older age group was significantly lower compared to the control group even after revaccination. A month after the first immunization, 4 people did not reach the protective level of anti-measles IgG. However, revaccination allowed them to form anti-measles immunity. In the course of our work, a case of non-response to vaccination was identified. Thus, our study showed a sufficient interindividual variability in humoral immune responses to measles vaccination.

This article presents two clinical cases of patients with a homozygous deletion of segment of chromosome 1, which covers regions of genes associated with complement factor H, in particular CFHR3. Patients underwent in-depth clinical studies, heredity assessment, laboratory, instrumental and genetic diagnostics. The first clinical case describes a clinical case with deleted chromosome 1 segment in a 9-year-old girl who was diagnosed with atypical hemolytic-uremic syndrome. This is a complement-dependent disease that affects both adults and children. It is known that a defect in any proteins included in the alternative complement activation pathway can lead to atypical hemolytic-uremic syndrome. However, this syndrome is most often caused by defects in chromosome 1 region, including gene sequences associated with complement factor H – CFHR1 and CFHR3. Modern treatment of atypical hemolytic uremic syndrome involves targeted pathogenetic treatment, therefore, the genetic diagnosis seems to be a necessary step for differential diagnosis and confirmation. The patient had fairly typical clinical symptoms, including signs of thrombotic microangiopathy, thrombocytopenia, hemolytic anemia and increasing renal failure. It is also known that her mother had congenital hydronephrosis, and the pregnancy proceeded against a background of ureaplasma, mycoplasma, cytomegalovirus infection, chronic pyelonephritis, and preeclampsia.

The second clinical case of a deleted chromosome 1 region, involving the CFHR3 gene, is a description of the disease in a boy of 8 years old, while the disease manifested with alopecia at the age of 4. Intermittent alopecia was the main symptom, while there were no signs of renal failure, thrombocytopenic purpura, and other symptoms characteristic of atypical hemolytic-uremic syndrome. The boy also revealed some congenital defects of the urinary system: bladder diverticulum, unilateral ureterohydronephrosis, and bilateral dilatation of the pyelocaliceal system. The detected genetic defect is usually associated with atypical hemolytic uremic syndrome. However, the phenotype, i.e., clinical manifestations, determined a completely different diagnosis – primary immunodeficiency, a group of complement defects, and a deficiency of complement factor H-related protein. After analyzing the given clinical cases, we can conclude that clinical manifestations may vary significantly in carriers of same gene mutations. This suggests that there are additional factors (genetic or environmental) that can influence the formation of various phenotypic manifestations of this pathology.

Hereditary angioedema (HAE) is a genetically caused orphan disease with a high risk of developing life-threatening attacks, thus requiring availability for up-to-date information on this problem for the doctors of any specialties. A limited number of observations determine the value of the analysis for each clinical case. Many facets of clinical manifestations, a list of predisposing and triggering factors, as well as limitations of some diagnostic and therapeutic algorithms, require the development of individual management schemes under distinct clinical situations. In this paper, we present the unique clinical cases with certain limitations, describing unexpected onset of the disease in the course of pregnancy, management aspects during delivery and post-delivery periods in a women with a previously confirmed HAE diagnosis. Adapted diagnostic algorithms of postnatal diagnostic verification are presented for children with burdened genetic history. We express some assumptions about involvement of a multidisciplinary team of specialists, personalized approach to building a management plan with an “online” correction depending on observation stage of НАЕ patient.

This paper presents comparative studies of preanalytical quality indices of vacuum gel systems (VGS) from four manufacturers, i.e., GL 795 (China), Vacuette (Austria), BD Vacutainer SST (USA) and Zdravmedtech (Russia). The analysis of the number of qualitative defects of the preanalytic phase of blood collection in vacuum gel tubes at the inpatient departments and in Department of Clinical Chemistry (preanalytic laboratory), in accordance with adopted criteria based on Russian industry standards, which are implemented with European indices of pre-analytic stage. The obtained results allowed us to identify a number of qualitative defects at pre-analytic stage for the vacuum gel systems from each manufacturer, including to summarize the data on number of these defects. Based on these results, the most common defects in each of the VGS presented by manufacturers are formulated. The results obtained can be used by manufacturers to improve the quality (structures) of the mentioned vacuum gel tubes.

The results of the comparative characteristics of VGS of different manufacturers were evaluated by their influence on the indexes of hemolysis (IH), ictericity, lipemia. The resulting indices of ictericity and lipemia do not allow to use them as criteria for assessing quality of the gel systems. The frequency of IH occurrence in serum at > 50 conventional units in VGS of different manufacturers was studied. It was revealed, that IH in the range from 10 to 50 conventional units and more, can be used as a criterion of VGS quality.

Comparison of routine biochemical parameters in VGS of different manufacturers, i.e., alanine aminotransferase, aspartate aminotransferase, direct bilirubin, lactate dehydrogenase (LDH), serum K+, was also carried out. It was found that the largest deviations from the average value were obtained for aspartate aminotransferase indices of more than 12.47% in Russian test tubes, and for direct bilirubin of more than 12.25% in Chinese test tubes and more than 9.15% in Russian test tubes. The study showed influence of IH upon quantitative values of lactate dehydrogenase for VGS from different manufacturers. It is proposed to use lactate dehydrogenase as an analyte. On this basis, it is possible to recommend a comparative quality assessment of vacuum gel systems, with IH cutoff level of more than 19 conventional units. It remains relevant to search for other analytes that can be used to assess the quality of VGS from different manufacturers. Some areas of research in biochemical testing are outlined. Preliminary data are obtained on usage of vacuum systems from different manufacturers for quality assessment, as well as conditions for performing these tests, along with the level of the hemolysis index of more than 10 conventional units.