Vol 27, No 3 (2024)

Hypoxia is connected with inflammation, and the severity of inflammatory diseases predominantly depends on individual tolerance to oxygen deficiency. Hypoxia-inducible factor, HIF-1, regulates the thymus functional state, and its activity varies in organisms with different hypoxia tolerance. It is likely that differences in individual hypoxia tolerance and the associated HIF-1 functional activity may influence the inflammatory diseases severity, such as acute and chronic ulcerative colitis. The study aim is to characterize the thymus morphological changes during acute and chronic colitis in animals with different hypoxia tolerance. The hypoxia tolerance of male C57Bl/6 mice was determined by “gasping time” at an “altitude” of 10,000 m in a decompression chamber. A month after determining hypoxia tolerance, the animals were modeled as acute colitis by replacing drinking water with a 1.5% dextran sulfate sodium for 5 days; the animals were removed from the experiment on the 7^th day. Chronic colitis was modeled by animals consuming a 1% dextran sulfate sodium on days 1-4, 12-14 and 22-26; animals were removed from the experiment on the 60^th day. The volume fraction of thymus structural and functional zones was assessed using the point counting method. The relative number of different thymic bodies types was assessed: consisting of 3-5 cells, 5 or more epithelial cells, with keratohyalin deposits and thymic bodies in the form of cyst-like cavities. During acute colitis, in the thymus only in susceptible mice, there was a significant cortex narrowing and an increase in the number of thymic bodies consisting of 5 or more cells. In chronic colitis, only in susceptible animals in comparison with the control group, the cortex volume fraction and the cortex to the medulla ratio increased significantly. In susceptible mice, the number of bodies with keratohyalin increased. In tolerant animals, the indicators did not change. Thus, differences in the thymus response to acute and chronic ulcerative colitis were identified between tolerant and susceptible to hypoxia animals. Only in susceptible mice, in acute colitis, was observed cortex narrowing, but in chronic colitis, cortex hyperplasia. The data obtained must be taken into account when conducting experimental studies of the thymus.

Acetaminophen is one of the most toxic drugs that can cause liver damage. At the same time, acetaminophen-induced liver failure is closely associated with the development of systemic inflammatory response syndrome. However, there is no drug aimed at suppressing the systemic inflammatory response. That is, this issue needs to be studied experimentally, but a model of systemic inflammation during acetaminophen overdose has not yet been obtained. Therefore, it was decided to develop an experimental model of systemic inflammation during acetaminophen overdose. The purpose of this study was to experimentally substantiate the semi-lethal dose for acetaminophen overdose in C57Bl/6 mice and to evaluate the readings of blood tests after administration of the drug. To determine the semi-lethal dose, male C57Bl/6 mice were intraperitoneally injected with “Ifimol” (Unique Pharmaceutical Laboratories, India) or acetaminophen solution (Sigma-Aldrich, USA) with a concentration of 14 mg/ml in different doses. When introducing “Ifimol”, it was not possible to achieve a semi-lethal dose. When administering a solution of acetaminophen, 50% mortality was recorded at a dose of 600 mg/kg body weight. After establishing a semi-lethal dose, the experimental group was administered an acetaminophen solution (Sigma-Aldrich, USA) with a concentration of 14 mg/ml at a dose of 600 mg/kg. The control group was injected with saline in an equivalent volume. On the second day, liver and peripheral blood samples were taken. Subsequently, hematological and biochemical blood tests and histological analysis were performed. Histological examination revealed centrilobular necrosis and disorganization of the liver structure. According to the biochemical blood test, the activity of aspartate aminotransferase, alanine aminotransferase, creatinine concentration, and the de Ritis coefficient differed statistically significantly (p < 0.05) in the experimental group compared to the control group. Among the hematological blood test parameters, there were statistically significant differences in the number of leukocytes, platelets, as well as the absolute and relative content of granulocytes and lymphocytes. Thus, 48 hours after administration of a semi-lethal dose of acetaminophen, there were signs of damage to internal organs (liver, kidneys) and changes in immune system parameters, which are similar to components of systemic inflammation in humans.

The goal is to study the effect of the synthetic peptide of the active center of the granulocyte-macrophage coline-stimulating factor ZP2 on the growth properties and biofilm formation of microorganisms of the genus Corynebacterium spp. In vitro experiments were carried out on 13 isolates of Corynebacterium spp., including C. amycolatum (n = 7), C. propinquum (n = 2) and C. pseudodiphtheriticum (n = 4)), previously isolated from healthy individuals and are part of the Network Collection of Symbiotic Microorganisms and Their Consortia of the Institute for Cellular and Intracellular Symbiosis UrB RAS (Orenburg, Russia). The effect of different concentrations of the ZP2 peptide on the growth properties (planktonic culture growth and biofilm formation) of test strains was assessed in 96-well polystyrene plates. The inhibitory effect of the ZP2 peptide on the growth of planktonic culture was assessed by the Inhibition Index (%), on biofilm formation – by the Degree of Inhibition of Biofilm Formation (%). It was experimentally established that after 2, 4, 6 and 24 hours, a dose-dependent inhibition of the growth of planktonic cultures of all studied bacterial strains was observed under the influence of various concentrations of ZP2 (0.5-2.0 μg/ml). In this case, the inhibitory effect of the ZP2 peptide depended both on its concentration in the cultivation medium and on the growth phase of the test strain of bacteria. The maximum inhibition of the growth of planktonic culture of all studied bacterial strains under the influence of various concentrations of the ZP2 peptide was observed after 24 hours and ranged from 89.3±1.9 to 94.1±1.8% in C. amycolatum, and in C. propinquum from 90.0±0.6 to 96.7±0.3%, in C. pseudodiphtheriticum from 92.2±2.1 to 95.1±1.3. The ZP2 peptide also had a significant effect on biofilm formation in all test cultures studied. The reduction in biofilm formation depended on the concentration of the peptide and ranged from 62.4 to 78.4% in C. amycolatum, from 70.9 to 79.6% in C. propinquum, and from 76 to 82.7% in C. pseudodiphtheriticum.

Thus, the antibacterial effect of the ZP2 peptide was revealed against the studied strains of corynebacteria species C. amycolatum, C. propinquum and C. pseudodiphtheriticum. According to available data, the ZP2 peptide is a drug with a wide spectrum of action that has an inhibitory effect not only on the studied actinobacteria, but also, according to literature data, on staphylococci and enterobacteria. An important prospect of the study is to reveal the mechanism of the antibacterial action of the ZP2 peptide with the characteristics of the effective concentration of the substance against pathogens and representatives of normal flora.

One of the trends in experimental and clinical immunology is the creation of new immunomodulators aimed at correcting various variants of the pathology of the immune system. Of interest are non-toxic, hormone-free and protease-resistant tetrapeptides, homologue of the of adrenocorticotropic hormone fragment (15- 18). There is little data in the literature on the effect of the above immunomodulators on the immunological parameters of the rat spleen on xenobiotic exposure models, which makes research relevant in this aspect. For the first time, the effect of tetrapeptides with laboratory ciphers KK1 and KK5 on the immunological parameters of the spleen of 36 female Wistar rats with passive smoking was evaluated. The experimental rats were fumigated with tobacco smoke for 8 hours daily for 20 days. Synthetic tetrapeptides were administered intranasally at a dose of 40 micrograms per kg/day, starting from the 10th day of the experiment. It was found that the studied tetrapeptides had a unidirectional positive effect on the immunological parameters of the spleen of experimental animals with passive tobacco smoking. This was expressed in a tendency to restore the pool of cells with CD3, CD4, CD8, CD20 markers to the level of the control group, as well as spontaneous and induced cytokine production by splenocytes. The shifts in the parameters of the spleen identified in this work may be based on a number of possible causes. Firstly, passive smoke causes a stress response in rats, which is confirmed by previous studies on a similar model, on an increase in the level of stress hormones in the blood serum of Wistar rats. Secondly, the literature data indicate the activation of lipid peroxidation during smoking. Thirdly, it is known that under the action of tobacco smoke toxicants, the lymphoid cell line suffers the most, since their polyhydrooxidized metabolites accumulate in the bone marrow and lymphoid organs, causing hypoplasia of the central and peripheral organs of immunity. A visible sign of this phenomenon is a decrease in the cellularity in the spleen, which is established in this work. Considering that active and passive smoking causes hypoxia and increases lipid peroxidation, the use of tetrapeptides KK1 and KK5 as agents that improve the body’s adaptation to hypoxia and increase resistance to stress damage is justified. Thus, the tetrapeptides KK1 and KK5 have a positive immunomodulatory effect, reducing the toxic stress effects of passive smoking.

SARS-CoV-2 infection can lead to pathological disorders in various organs due to the ubiquitous of angiotensin-converting enzyme 2 (ACE2), which serves as a receptor for SARS-CoV-2. However, tissue damage may not only be the result of viral infection. SARS-CoV-2 has been shown to induce the production of autoantibodies to ACE2, and their presence is associated with disease severity. The spleen is one of the targets for COVID-19. The presence of ACE2 in the red pulp sinus endothelium cells of the spleen and in tissue-resident CD169⁺ macrophages positioned in the splenic marginal zone makes these cells a potential target of autoimmune reactions to ACE2 triggered by SARS-CoV-2. In addition, antibodies to the SARS-CoV-2 S protein cross-react with a wide range of human tissue proteins and can cause tissue damage. The most common splenic pathologies in deceased COVID-19 patients are lymphocyte depletion and subsequent hemaphagocytosis. Since the spleen plays a fundamental role in the immune response regulation, splenic damage could be one of the causes of immune perturbations associated with severe COVID-19. To test the hypothesis of the autoimmune nature of COVID-19, we developed a non-infectious experimental model of autoimmune multiorgan damage caused by immunization with SARS-CoV-2 S protein. The purpose of this work was to study the spleen in rats with induced multiorgan damage caused by immunization with SARS-CoV-2 S protein, as well as the influence of pre-existing autoimmune disease on the severity of splenic damage caused by an immune response against S protein. Intact Wistar rats and Wistar rats with completed experimental autoimmune encephalomyelitis were immunized with S protein in incomplete Freund’s adjuvant (IFA). Control rats received an injection of IFA. No changes were detected in the secondary follicles number in the spleen of rats immunized with the SARS-CoV-2 S protein. However, in the spleen of rats with previously induced autoimmune encephalomyelitis, immunization with SARS-CoV-2 S protein caused a significant decrease in the number of secondary follicles relative to the control group. Hemosiderin deposits and macrophage hyperplasia of the marginal zones of the white pulp were detected in both groups immunized with S protein. Thus, immunization with the S protein of SARS-CoV-2 causes changes in the spleen of rats similar to those detected in patients who died from COVID-19. Damage to the spleen is more varied and pronounced in rats with previous experimental encephalomyelitis.

The purpose of the study was to study the cytokine-producing function of cumulus cells of the ovaries in PCOS during co-cultivation of cumulus cells with mast cells to identify their mutual influence in the immunopathogenesis of PCOS.

The study was approved by the Interdisciplinary Ethics Committee of the FSBEI of HE of the Ministry of Health of the Russian Federation. A permanent human mast cell line HMC-1 (Human mast cell, ATCC, USA) and a primary culture of cumulus cells were used. The condition of cumulus cells and mastocytes was determined using fluorescent dyes followed by flow cytometry before co-cultivation and after 7 days co-cultivation. The levels of IL-6, IL-10, and IFNã were studied on days 1, 3, and 7 of the experiment.

In monoculture and during co-culture of cells, the synthesis of cytokines IL-6, IL-10, and IFNã continues, but to varying degrees of severity. In the permanent mast cell line, an increase in IL-6, IL-10, and IFNã is observed on the 1^st, 3^rd, and 7^th days of cultivation. On the first day, cytokine levels of donor cumulus cells and mastocytes did not differ significantly (p > 0.05). In the culture of donor cumulus cells, the synthesis of IL-6, IL-10, and IFNã progressively increases by the 7^th day of the experiment (p < 0.05). On the first day of the experiment, the balance of Th1/Th2 cytokines in PCOS was twice as high as in healthy women. The ratio increased, and on the 7^th day reached 3.83 times higher than the ratio of Th1/Th2 cytokines in the control group. Hyperproduction of IFNã by mastocytes was most significant when they were co-cultured with cumulus cells, in monoculture mast cells synthesized excessively cytokine twice from the initial values of IFNã, and the monoculture cumulus cells in PCOS it practically did not contain.

The studied cytokines are regulators of the function of ovarian cumulus cells and factors that increase the competence of the oocyte, indicating the need for their correction, which will allow a real influence on the links of pathogenesis in PCOS in the future.later on.

Atherosclerosis is a multifactorial process involving various pathological mechanisms: inflammation, lipoprotein modification, cholesterol accumulation, endothelial dysfunction, oxidative stress and formation of atherosclerotic plaque. The main participants in the development of this disease are endothelial cells, leukocytes and smooth muscle cells of intima. The adult endothelium contains heterogeneous cells, including typical endothelial cells (TEC) and giant multinucleated EC variants (MVEC). The process of passing molecules is called transendothelial transport (TET). The purpose of this work is to model the processes of TET of low-density lipoproteins (LDL) and monocyte migration using various EC variants. In the study, a human EC line (EA.hy926) was used. Multicore variants of EC (MVEC) were obtained by treating EC with a 50% solution of polyethylene glycol 6000. To study LDL transcytosis and monocyte migration, tablets with inserts (0.4 or 3.0 micron pore diameter, respectively) forming a two-level system were used. The LDL transmission rate was assessed by measuring the amount of cholesterol in the upper and lower chambers every 2, 5 and 24 hours. A modified Folch method was used to measure the amount of cholesterol. The cholesterol content was adjusted according to the total protein level in the well, measured by the Lowry method. The migration of macrophages was estimated by direct counting of cells. The content of internalized cholesterol in the MVEC was statistically significantly higher than in the EC. The rate of LDL transport did not differ. The rate of passage of the endothelial barrier formed by MVEC by macrophages was higher at points 2 and 5 hours. After 24 hours the number of migrated cells did not differ. The rate of transendothelial transport for typical and multinucleated variants of EC did not statistically differ. Although the presence of MBEC does not affect the transport of lipoproteins into the subendothelial layer, the fact that multinucleated cells accumulate lipid droplets more actively than typical ECS may indicate an important role in the pathogenesis of atherosclerosis. The rate of macrophage migration after 2 and 5 hours was higher for MVEC than for TEC, whereas immature macrophages did not migrate through the endothelial barrier for 24 hours.

The purpose of this work is to attempt to provide an overview of current recommendations for the diagnosis and treatment of familial Mediterranean fever, as well as to present our own clinical observation of this pathology.

A selective analysis of the literature over the past 5 years (2020-2024) was carried out in the scientometric databases PubMed (https://pubmed.ncbi.nlm.nih.gov) and the Russian Science Citation Index (www.elibrary.ru).

Current data on the autoinflammatory disease familial Mediterranean fever are reviewed. It is important to understand the fact that this pathological condition can be combined with a wide range of autoimmune diseases. The lack of therapy is dangerous for the development of serious complications (systemic amyloidosis). Attention is drawn to the use of colchicine, as well as in the case of colchicine resistance and insufficient effectiveness of colchicine – IL-1 inhibitors. We present our own clinical observation of this disease with an emphasis on the features of the course and stages of therapy for this pathology. A young man, Armenian, was treated for 3 years due to acute conditions with an increase in body temperature to febrile levels, severe abdominal pain and moderate arthralgia. The conditions were accompanied by leukocytosis and increased CRP, but no signs of acute surgical disease were detected. After a molecular genetic study, the diagnosis of familial Mediterranean fever was verified. Colchicine was prescribed, which helped stop many manifestations of the disease; she has been taking it regularly for 5 years. Currently, episodes of exacerbations have become significantly less frequent, laboratory markers of acute inflammation have normalized, but the use of colchicine in the maximum daily dose causes abdominal discomfort. Rare episodes of exacerbations during treatment suggest insufficient effectiveness of this drug. An option to achieve results in such a situation is to use a class of genetically engineered biological drugs such as IL-1 inhibitors.

Familial Mediterranean fever is a rare pathological condition, but doctors of various clinical specialties should be wary of its detection. Achieving treatment success requires constant monitoring of the patient’s condition, prescribing therapy with colchicine or IL-1 inhibitors from the moment of diagnosis.

Atherosclerosis is the most common chronic non-infectious diseases, in the pathogenesis of which the accumulation of lipids in the subendothelial layer of the arteries and the local inflammatory reaction play a significant role. The source of lipid accumulation in the vascular wall is modified low-density lipoproteins. Desialylation is one of the known modifications that leads to the emergence of atherogenic properties in low-density lipoproteins. Enzymes that have sialidase activity circulate in human blood, i.e., the ability to cleave sialic acid from low-density lipoproteins. Desialylated low-density lipoproteins are autoantigens and induce the production of IgG autoantibodies, which form immune complexes with low-density lipoproteins, which aggravates the course of atherosclerosis. The purpose of the study was to establish associations between the levels of sialic acid in low-density lipoproteins, sialidase activity and the cholesterol content of lipid-containing circulating immune complexes in the blood serum of patients with atherosclerosis. Blood sera from patients with coronary heart disease were used as biological material to determine indicators of sialidase activity, cholesterol content of lipid-containing circulating immune complexes and sialic acid in low-density lipoproteins, which were isolated from blood serum. Serum samples were obtained from the laboratory of clinical biochemistry of the Institute of Clinical Cardiology, A.L. Myasnikov Federal State Budgetary Institution National Medical Research Center of Cardiology named after Academician E.I. Chazov as unutilized residues after performing routine biochemical tests. Fifty-one samples of blood serum and low-density lipoproteins isolated from it were analyzed. A significant positive relationship was revealed between the cholesterol content of circulating immune complexes and sialidase activity in the blood serum (r = 0.305 at p = 0.029). At the same time, no correlation was found between the content of sialic acid in low-density lipoproteins and sialidase activity in the blood serum, as well as between the cholesterol content of circulating immune complexes in the blood serum and sialic acid in low-density lipoproteins. It should be assumed that increased sialidase activity in the blood serum leads to the formation of desialylated immunogenic low-density lipoproteins with the subsequent appearance of autoantibodies and the formation of lipid-containing circulating immune complexes.

Obesity has been a global health problem over the past decades. The search for new ways in the fight against overweight and obesity leads to a deeper understanding of the pathogenetic mechanisms underlying this condition, and with each new study, the understanding of the problem expands first of all from the immunological approach. Despite the active study of the WNT signaling system in recent years, the available literature contains a small number of studies devoted to determining the components of this signaling pathway in the blood serum of obese people, and virtually no studies on WIF-1 and DVL-1. Purpose of the work: to study DVL-1 and WIF-1 in the blood serum of overweight and obese individuals. Patients (n = 210, aged 19 to 65) were examined, divided into 4 groups: I – people with normal body weight, II – patients with excess body weight; III – patients with metabolically healthy obesity, and IV – patients with metabolically unhealthy obesity using general clinical and immunological research methods. The study obtained data on the concentrations of DVL-1 and WIF-1 in the blood serum of patients with overweight, metabolically healthy and unhealthy obesity, and described the correlation between these proteins of the WNT-signaling pathway and clinical and laboratory parameters. In obese patients, statistically significant changes in the values of the components of the WNT signaling system in the blood serum were detected: an increase in the level of DVL-1, as well as an increase in the level of WIF-1 with an increase in the degree of obesity in metabolically healthy individuals. Correlations between DVL-1 and lipid spectrum indicators; between WIF- 1 with cholesterol profile, leukocytes and erythrocyte sedimentation rate were revealed. The pathogenesis of obesity is a complex process in which various immunopathological mechanisms, where the WNT signaling pathway plays one of the leading roles. Although some of the effects mediated by DVL-1 and WIF-1 have recently been elucidated, the details of their integration are a missing link that must be further explored for better understanding of the immunopathogenesis of metainflammation in obesity.

As a result of examinations of the indigenous population of different ages in Abkhazia, 103 of the healthiest patients were selected, divided according to WHO classifications into four age groups: group 1 – young age (18-44 years, n = 37), group 2 – middle age (45-59 years, n = 13), group 3 – elderly (60- 74 years old, n = 27) and group 4 – senile (75-89 years old, n = 26). To assess the health status of those observed, along with the clinical examination, a number of laboratory tests were carried out: hematological, hemostasiological, biochemical, the concentration of pro- and anti-inflammatory cytokines were determined; instrumental diagnostics were used, when needed. The examination was carried out after the informed voluntary consent of the patients. Almost to all senile and sometimes elderly patients were paid home visits. The criteria for exclusion from the study were significant deviations from the norm in the studied laboratory blood parameters, exacerbations of chronic diseases and the presence of acute infectious diseases at the time of the examination. The phagocytic activity of neutrophil granulocytes (NG) was determined by flow cytometry using an EPICS XL cytometer (Beckman Coulter, USA) using the FagoFlowEx^® Kit (Czech Republic) designed to assess absorption (percentage of actively phagocytic NG) and digestion (NG stimulation index) NG abilities after stimulation with E. coli in heparinized whole blood samples. When comparing leukocytes, no statistically significant differences were revealed between the four age groups compared: young, middle, elderly, and senile (p = 0.795). The absolute content of NG in the peripheral blood of the examined groups did not differ significantly, while the percentage ratio had a significant difference between the elderly and senile groups (p = 0.019). When assessing the absorptive capacity and determining the percentage of FAN depending on age, statistically significant differences were established between the young and senile age groups (p = 0.038). When comparing the oxygen-dependent digestive activity of NG, the stimulation index, depending on age, statistically significant differences were also established between the young and old age groups (p = 0.014). No significant differences between other age groups were found in terms of % FAN or IS. Thus, among the age groups examined, we identified a statistically significant weakening of both the absorption and oxygen-dependent digestive phagocytic activity of neutrophil granulocytes in the senile group, which turned out to be the most vulnerable according to the studied indicators.

The nature of changes in the immune system during physical work is a complex process involving many different mechanisms. Research in this direction is an urgent problem. The purpose of the research was to study the indicators of cellular and humoral immunity in students with different levels of physical activity. A total of 77 male students were examined, consisting of 3 groups: 1) with a low level of physical activity (n = 32) – students who were not involved in sports activities on a regular basis; 2) students with an average level of physical activity (n = 22) – beginner sambo wrestlers without sports categories; and 3) students with a high level of physical activity (n = 23) – highly qualified sambo wrestlers – first-class athletes, candidates for masters and masters of sports. In students of all groups, the quantitative content of various phenotypes of lymphocytes in the blood was studied by flow cytometry; serum immunoglobulin levels by laser nephelometry; phagocytic parameters by traditional methods; and oxygen-dependent metabolism of neutrophils by chemiluminescence. In students with a high level of physical activity, the content of T and B lymphocytes in the blood was significantly increased compared to similar indicators of the group with a low level of physical activity and the group of students who did not participate in sports. The concentration of class G immunoglobulin in the blood serum of students with a high level of physical activity significantly exceeded the corresponding values in students with an average level and students not engaged in sports. The highest concentration of class M immunoglobulin was observed in students with high levels of physical activity. Phagocytic activity and phagocytic count in individuals with high levels of physical activity and neutrophils were significantly higher than those of students with medium and low levels of physical activity. The rates of spontaneous and induced chemiluminescence in the groups with high and medium levels of physical activity were significantly higher than in students with low levels. The studies carried out indicate the positive effect of regular training physical activity on the factors of humoral and cellular links of immunity in students in the conditions of the educational environment of a higher educational institution.

Post-traumatic stress disorder in combat veterans has certain characteristics common to combatants. B lymphocytes may aggravate neurocognitive impairment by demonstrating a significant proinflammatory tendency through the production of immunoglobulins and a number of proinflammatory factors. Objective: to study the phenotypic heterogeneity of B lymphocyte subpopulations in veterans with post-traumatic stress disorder.

Studies were conducted in a cohort of veterans of the special military operation in Ukraine (SVO), including 26 combatants with clinically verified PTSD who made up the main (1) group, and 30 veterans were included in the comparison group (2). The diagnosis was verified on the basis of neuropsychological and pathopsychological examination. Determination of IL-10 levels (pg/mL) using a multiplex analysis on a Luminex Magpix 100 immunoanalyzer (USA) using the Bio-Plex multiplex analysis test system (MERZ, Germany) was performed. Gating of the B lymphocyte population was performed on a Navios flow cytofluorimeter (Beckman Coulter, USA) using a standardized technology for assessing the lymphocyte component of immunity.

In the group of SVO veterans with PTSD, we showed an increase in blood cells with the CD45⁺CD3^-CD19⁺CD5⁺ phenotype in comparison with the indicators of groups 2 and 3. B lymphocytes expressing the CD5⁺ marker are found in various human tissues and can also produce autoantibodies. Analysis of subpopulations of B lymphocytes with markers of memory cells showed a significant decrease in the blood of SVO veterans in the total number of memory B lymphocytes (CD45⁺CD3^-CD19⁺CD27⁺), against the background of an increase in the concentration of cells positive for CD5 and CD27 with the phenotype CD45⁺CD3^-CD19 ⁺CD5⁺CD27⁺CD27⁺. B cells play a critical role in the mechanisms of intercellular interaction.

The phenotypic diversity of B lymphocyte subpopulations that we have established in veterans with post-traumatic stress disorder is characterized by an increase in the circulation of B lymphocytes with CD5 and CD27 molecules, against the background of a general decrease in memory B cells. This indicates a possible autoimmune orientation of neuroinflammatory processes in the brain, associated both with a stress-induced increase in the permeability of the blood-brain barrier, and with the need to control excessive activation of immunocompetent cells.

Schizophrenia is a severely disabling and clinically heterogeneous disease that manifests with disorders of thinking, motivation and emotions. Negative symptoms of schizophrenia include decreased expression of emotions, poverty of speech, withdrawal from social contacts, anhedonia. They poorly respond to therapy, and their severity has the most significant impact on the functioning and quality of life of patients. Changes in systemic immunity in schizophrenia with pronounced negative symptoms are poorly studied. We have previously shown the relationship of elevated levels of interleukin-10 (IL-10) with the severity of negative symptoms and with morphometric changes in the brain in schizophrenia. The aim of this study was to investigate the relationship of a number of systemic immunity parameters (regulatory and proinflammatory cytokines and indicators of cell immunity) with the severity of negative symptoms and the disease severity in schizophrenia. The study included 94 patients treated in the Psychiatric Clinical Hospital No. 1 named after N.A. Alekseev, 66 of whom had pronounced negative symptoms. The control group consisted of 24 healthy volunteers. ELISA and multiplex analysis were used to determine cytokine levels, and multicolour flow cytometry was used to determine the parameters of cellular immunity. The level of circulating immune complexes was determined by immune turbodimetric analysis. Differences were considered statistically significant at p < 0.05. The results of the study showed that the majority of schizophrenia patients, regardless of the severity of negative symptoms, had an increase in the levels of cytokine IL-8. It was shown that the severity of negative symptoms was associated with increased levels of cytokines IL-10, IL-12p40, IL-17E/IL-25 and IL-34. It was also revealed that patients with pronounced negative symptoms had a higher level of CD3^-CD19^-B cells compared to the control group, which, taking into account the changes of the cytokine profile, indicate possible activation of the B cell link of humoral immunity. The data obtained in this work indicate that in schizophrenia with pronounced negative symptoms and severe course of the disease, there is activation of immunoregulatory and Th2-mechanisms. The results contribute to the understanding of the role of immunity disorders in the pathogenesis of various clinical forms of schizophrenia.

Neuroinflammation during intracerebral hemorrhage is initiated by blood breakdown products in the subarachnoid space and/or brain parenchyma. In this case, neuroinflammation can cause the development of systemic inflammation. In some cases, intracerebral hemorrhage is accompanied by the appearance of the phenomenon of ineffective cerebral blood flow and clinical manifestations of brain death. The purpose of the study is to identify markers of systemic inflammation in severe hemorrhagic stroke with or without effective cerebral blood flow. The study included patients with intracerebral hemorrhage and the presence of multiple organ failure syndrome, as well as coma on the first day of manifestation, to determine markers of systemic inflammation. A total of 3 groups were analyzed: patients with ineffective cerebral blood flow (Group 2); with effective cerebral blood flow (Group 3); and control group (Group 1) – healthy blood donors. Criteria for non-inclusion in the study: the presence in patients with hemorrhagic stroke of septic complications during hospitalization and acute infectious diseases during the manifestation of intracerebral hemorrhage. In frozen blood plasma samples (anticoagulant – citrate), the levels of IL-6, IL-8, IL-10, TNFá, procalcitonin, neuron-specific enolase, cortisol, myoglobin, troponin I and D-dimers were determined. Enzyme immunoassay was carried out on an automatic analyzer “Dynex Lazurite” (Dynex Technologies, VA, USA). The Kolmogorov–Smirnov test was used to confirm the normality of data distribution. Further comparison of quantitative data was carried out using the nonparametric Mann–Whitney U test. All results were considered statistically significant at p < 0.05. In patients with effective and ineffective cerebral blood flow, statistically significant differences were observed in almost all studied markers of systemic inflammation, except for troponin I. However, in the presence of effective cerebral blood flow, significantly higher values of a number of indicators were noted, which may indicate a more rapidly occurring acute systemic inflammatory response in case of effective cerebral blood flow. At the same time, 28 day mortality and SOFA scores in the group with effective blood flow were lower than in the group with ineffective blood flow. This discrepancy may indicate a greater contribution to 28 day mortality and patient severity from direct loss of brain function than from systemic inflammation in patients with ineffective blood flow. On the other hand, the lack of severity of systemic inflammation in this category of patients is most likely due to impaired blood outflow from the damaged brain and the entry of tissue breakdown products and other pro-inflammatory factors into the systemic circulation. That is, intracerebral hemorrhage is accompanied by the development of neuroinflammation, which may be an important component of systemic inflammation. However, disruption of the inflow and outflow of blood in the main great vessels of the brain reduces the likelihood and severity of the development of systemic inflammation.

Chronic rhinosinusitis is a disease caused by inflammation of the paranasal sinuses and its mucous membrane with a duration of symptoms of the disease of more than 4 weeks continuously. The purpose of our study was to study the cellular and humoral components of immunity in CRS and comorbid conditions. This study was conducted at the Research Institute of Medical Problems of the North, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences, Krasnoyarsk, Russian Federation. A total of 91 patients with chronic rhinosinusitis were selected, of which 30 people were patients with isolated chronic rhinosinusitis, 25 people were with chronic rhinosinusitis and deviated nasal septum, 19 people were with chronic rhinosinusitis and chronic rhinitis, and 17 people were with chronic rhinosinusitis and bronchial asthma. The control group consisted of 35 practically healthy blood donors comparable in gender and age to the study groups, who underwent a routine examination at the institute’s clinics. To study systemic cellular immunity in venous blood, flow cytometry was used on a Cytomics FC500 flow cytometer (Beckman Coulter, USA). To stain lymphocytes, monoclonal antibodies (MAbs) were used: CD3⁺, CD4⁺, CD8⁺, CD16⁺, and CD19⁺, from Beckman Coulter (USA). With CRS and deviated nasal septum, changes were detected in the form of an increase in the absolute content of B lymphocytes and a decrease in 3 relative synthesis indices. In CRS and chronic rhinitis, an increase in the absolute content of B lymphocytes and a decrease in the relative number of T helper cells and 3 relative synthesis indices were found. In CRS, an increase in the content of B lymphocytes and IgE was detected (but the value was below 100 IU/mL), and a decrease in the relative number of T helper cells and 3 relative synthesis indices. In CRS and bronchial asthma, there was an increase in the absolute content of T helpers, B lymphocytes, hypergammaglobulinemia in classes A and E (more than 100 IU/mL) and a decrease in the relative number of T helper cells, the absolute number of cytotoxic T lymphocytes and 3 relative synthesis indices.

The visual analogue score (VAS) is recommended to assess the severity of symptoms of allergic rhinitis (AR), but despite its advantages, it is a tool for subjective assessment of symptoms and often does not correlate with the true state of nasal patency. Anterior active rhinomanometry (AAR) is the method to objectify obstructive changes in the nasal cavity in patients with AR and is the most accurate method to assess nasal breathing function from a physiological and aerodynamic point of view. In addition, AAR with a decongestant test allows a differential diagnosis of the causes of nasal obstruction. Our study showed that there was no correlation between VAS and AAR scores. In addition, we found the importance of performing AAR with a decongestant test and subsequent assessment of unilateral flow and resistance parameters, which allowed us to suspect the presence of structural changes in the nasal cavity in patients with AR, as recorded as a result of anterior rhinoscopy and/or endoscopic examination. Thus, in addition to the use of VAS, it is necessary to include AAR in the diagnostic algorithm for AR, which allows not only to confirm the presence or absence of nasal breathing impairment, but also to differentiate the causes of its occurrence for the subsequent selection of the optimal management of patients with AR.

Despite the enormous successes that have been achieved in the fight against infectious diseases thanks to mass preventive vaccination, primarily the reduction of child mortality, оutbreaks of vaccine-preventable diseases sometimes occur. One of the reasons is unjustified medical exemptions from vaccinations, which were widely used in the past, the shortcomings of taking into account adverse events after immunization as well as parental refusals (complete or partial) from preventive vaccinations. The article presents data from a retrospective analysis of medical records of patients sent for consultation with an allergist-immunologist to decide on the possibility of vaccination against the new coronavirus infection (COVID-19), including to confirm previously issued medical exemptions. The study included 87 patients (39 men and 48 women), most of them were of working age. Sixty-eight patients (78.2%) had previously received medical exemptions from vaccination, including 14 (20.6%) based on information about adverse events after immunization, and 32 (47.1%) based on adverse reactions for the administration of other medications, and in 22 (32.3%) only on the basis of a diagnosis of any allergic disease. At the same time, medical documentation confirming the facts of adverse events after immunization or adverse reactions to medications was absent in the vast majority of cases. In addition, 3 patients were not vaccinated in childhood due to parental refusal, and another 16 patients were contacted to assess the potential risk of developing side effects after vaccination due to the presence of allergic diseases (bronchial asthma, allergic rhinitis, atopic dermatitis, chronic urticaria, recurrent angioedema). Based on clinical and anamnestic data and, if necessary, laboratory and instrumental studies, temporary contraindications for vaccination were identified in only 6 (27.2%) patients. There were no absolute contraindications. In other cases, stable remission was observed or the disease was fully or partially controlled with medication, which was not a contraindication for vaccination at the time of treatment. Thus, in most cases, medical exemptions from vaccinations are unfounded or become irrelevant over time. At the same time, the lack of medical documentation seriously makes it difficult to objectively assess the risk of developing adverse events after immunization in patients with allergic diseases.

Cluster of differentiation 14 (CD14) is a pattern recognition receptor for lipopolysaccharide of gram-negative flora and has a close relationship with toll-like receptor 4 (TLR4). The interaction between CD14 and TLR 4 leads to the synthesis of cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor-á. The TLR4 receptor is associated with the penetration of the new coronavirus infection virus into the cell, additionally stimulating the expression of the angiotensin converting enzyme 2 molecule and suppressing apoptosis in infected cells. Work on the study of the (159C)T polymorphism of the CD14 gene in COVID-19 is represented by only a few publications describing observations only in the Western European region. The purpose of our study was to study the association between single nucleotide polymorphism (SNP) of the CD14 gene – (159C)T (rs2569190) and susceptibility to a new coronavirus infection in the population of the Republic of Crimea. The study included 158 patients (87 women (55%) and 71 (45%) men, average age 45.6±6.14 years) who had COVID-19. Verification of previous COVID-19 was based on anamnestic data and data from studies performed at the time of illness (PCR). The control group consisted of 85 respondents who had not suffered a new coronavirus infection. To analyze the (C-159)T polymorphism of the CD14 gene, allele-specific PCR with electrophoretic detection in a 3% agarose gel (NPF "Litekh", Russia) was used. To compare the frequencies of allele combinations, the ÷² test and odds ratio (95% CI) were used. The distribution of CD14 mutations followed Hardy-Weinberg equilibrium (p > 0.05). The results of the study showed that the distribution of CD14 gene genotypes did not differ significantly in all study groups. The dominant genotype was the heterozygous genotype CT of the (C-159)T polymorphism of the CD14 gene. The analysis showed that the presence of CT and TT SNPs was not associated with the risk of developing a new coronavirus infection (p > 0.05). Conclusions. The CD14 SNP (C-159)T is not associated with a higher risk of COVID-19 infection. The distribution of occurrence of SNP variants in the group of recovered individuals did not differ significantly from that in the control group (p > 0.05).

The immune system is sensitive to the effects of environmental factors, and according to numerous studies, lead has an immunotoxic effect. At the same time, there is evidence of the multidirectional nature of the impact of lead on the immune system, determined by the degree of exposure to this heavy metal, which makes it current to study changes in immunological markers in workers of a modern lead recycling plant, taking into account levels and complexity of exposure. In the era of personalized medicine, monitoring the potential influence of occupational factors exposure on the immune system can facilitate a personalized approach to the prevention of work-related health conditions. The aim of the study: to evaluate changes in immune status markers among employees of lead recycling plant. The main group – 62 men working at a lead recycling plant, the control group – 47 men not exposed to occupational factors. Laboratory examination included a determination of the lead blood level, a clinical blood test, the serum levels of IL- 1â, IL- 10, IL- 8, MCP-1, C3 and C4 complement components, IgA, IgM, IgG. In the main group, compared to the control group, a higher number of neutrophils, lymphocytes, monocytes, higher levels of IL-8, C3 and C4 components of the complement system, and lower levels of IgM were detected. In the main group, the following changes in markers were significantly more often detected in comparison with reference values: an increase in the C3 component of complement (51.6% in the main group compared to 12.5% in the control group), decreased IgG (24.2% compared to 6.2%) and increased IgA (22.6% compared to 6.2%). Associations were identified between the lead blood level and the number of lymphocytes, the level of IgG, between work experience in contact with lead and the level of MCP-1 and C3 complement components. The results of the studies revealed the presence of changes in the immune status markers of workers at a lead recycling plant, which demonstrate a proinflammatory effect of lead and an influence on the humoral immune status. The identified changes in immunological parameters may underlie the mechanisms of formation of pathological conditions associated with lead exposure, which determines the relevance of continuing research to assess dynamic changes in immunological parameters and develop a system for monitoring the immune status of workers exposed to lead and its compounds to optimize preventive measures.

Preterm birth (PB) carries a high risk of developing neuropsychological development disorders, cognitive and somatic problems in the child. The maternal immune system plays a critical role in maintaining a physiological pregnancy. However, specific mechanisms and disorders of pregnancy development have been little studied. There is a lack of research on the role of immune competent cell (ICC) activation in preterm labor leading to uterine contractility. Understanding the importance of immune system factors in the formation of preterm birth may allow the development of strategies to prolong pregnancy and, thus, lead to improved perinatal outcomes. The purpose of the work is to study the role of immune factors in the development of preterm birth. Seventy pregnant women in the third trimester with recurrent miscarriage (RPL) and 25 healthy pregnant women (control group) were examined. Observed pregnant women with RPL were divided into two groups: Group I – patients who gave birth prematurely (n = 30); and Group II – patients who gave birth at term (n = 40). The population and subpopulation composition of peripheral blood lymphocytes was studied by cytofluorimetry using monoclonal antibodies to: CD3, CD4, CD8, CD16, CD19 (JSC "Sorbent", Russia) (FITC), CD11b (Beckman Coulter, USA); CD14, CD25, CD69, CD71, CD28, CD107a, HLA-DR (Beckman Coulter, USA) (PE). To create a database and conduct statistical research, the capabilities of an Excel spreadsheet and application packages (Megastat and Statistica 6.0) were used. When determining statistical significance between the study groups, the Mann-Whitney test was used for independent groups and the Wilcoxon test for dependent groups.

Modulation of the number and functional activity of ICC in patients with RPL had a significant correlation with pregnancy outcome. Inadequate activation of the immune system is a factor that can lead to miscarriage. Termination of pregnancy before term is associated with subpopulation shifts, increased activation potencies of immunocompetent cells compared to full-term birth, which is an important feature of the inflammatory response. The identified immune changes will allow the development of early prevention methods and new approaches to the treatment of this pregnancy complication.