Russian Journal of Immunology
Peer-review quarterly medical journal.
Editor-in-chief
- Prof. Valeriy A. Chereshnev, MD, Dr. Sci. (Medicine)
ORCID iD: 0000-0003-4329-147X
Publisher
- Russian Society of Immunology
WEB: https://rnoi.ru/
About
Founded in 1996.
“Russian Journal of Immunology” is a scientific and educational journal in the field of fundamental and clinical immunology, the purpose of which is to promote the scientific achievements of fundamental and clinical immunology for various fields of medicine, publish reviews, lectures, articles by leading domestic and foreign experts in the field of fundamental and experimental immunology, clinical immunology, allergology, immunodiagnosis and immunotherapy of infectious, allergic, autoimmune and oncological diseases.
The journal is distributed throughout the territory of the Russian Federation and CIS countries. The journal is included in the register of subscriptions: in the catalog "The Russian Press" - 15590.
Indexation
- Russian Science Citation Index (Web of Sciences)
- Russian Science Electronic Library (eLibrary.ru)
- Google Scholar
- Ulrich's Periodicals directory
- WorldCat
- Crossref
Types of accepted articles
- reviews
- systematic reviews and metaanalyses
- original research
- clinical case reports and series
- letters to the editor
- short communications
- clinial practice guidelines
Publications
- in English and Russian
- quarterly, 4 issues per year
- continuously in Online First
- with NO Article Processing Charges (APC)
- distribution in Open Access with the Creative Commons Attribution 4.0 International License (CC BY 4.0))
Announcements More Announcements...
Russian Journal of Immunology has been transferen to the Eco-Vector online publishing platformPosted: 19.02.2022
From February 2022, the Russian Journal of Immunology has been transferen to the Eco-Vector online publishing platform. We would like to thank the Eco-Vector employees for prompt and high-quality content transfer. The journal archive and all services of the electronic editorial system are active and functional. We look forward to a long and fruitful cooperation! |
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Current Issue
Vol 27, No 3 (2024)
- Year: 2024
- Published: 25.09.2024
- Articles: 42
- URL: https://rusimmun.ru/jour/issue/view/34
Full Issue
SHORT COMMUNICATIONS
Thymus morphological characteristics in acute and chronic colitis in animals with different hypoxia tolerance
Abstract
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 7th 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 60th 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.
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Effect of leptin and adiponectin on the expression of cytokine genes IL-1β, IL-6 AND TNFα in lymphocytes
Abstract
Metabolic syndrome (MS) is one of the world’s topical health problems. Large-scale epidemiological studies on the prevalence of MS in the world have not been conducted, but according to different authors, depending on the region of residence, the composition of the study population and the diagnostic criteria used, the incidence of MS is at least 10%, and according to estimates of the International Diabetes Federation IDF – up to 25% of the adult population. The metabolic changes in MS are explained by a disturbance in the balance of mediators synthesized by adipose tissue (adiponectin, leptin, resistin, visfatin, vaspin and others); MS is also considered as a subclinical chronic inflammatory process characterized by excessive synthesis of proinflammatory and deficiency of anti-inflammatory cytokines. According to modern ideas, changes in the cellular and humoral immunity in MS are largely due to the imbalance of adipokines: leptin and adiponectin. Increased functional activity of immune cells, including lymphocytes, leads to changes in cytokine gene expression. In the present work, we studied in vitro the expression of IL-1â, IL-6 and TNFá genes in peripheral blood lymphocytes under the influence of adipokines at concentrations characteristic of MS. As a result, differential effects of adipokines on lymphocytes of MS patients and conditionally healthy individuals were found. In conditionally healthy individuals, incubation of lymphocytes with adipokines leptin, adiponectin and their combination, as well as in the presence of physiological solution causes an increase in IL-6 gene expression. The most noticeable effect was observed when cultured with adiponectin. Thus, in norm, with a decrease in the physiological concentration of adiponectin, the expression of IL-6 in lymphocytes increases, indicating insufficient realization of the anti-inflammatory effect of adiponectin. In MS, IL-6 gene expression increases in lymphocytes isolated from peripheral blood in vitro after incubation with adiponectin, a combination of adiponectin and leptin, as well as in the presence of physiological solution. No changes in IL-6 gene expression under the effect of high concentration of leptin were detected.
Probably, our results reflect the phenomenon of lymphocyte resistance to leptin action in MS, as under its influence there is not activation of lymphocytes characteristic in vivo, but on the contrary, decrease of activated subpopulations, also there is no change in IL-6 gene expression. Thus, adipokines in concentrations characteristic of metabolic syndrome influence the functional activity of peripheral blood lymphocytes.
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Experimental model of systemic inflammation during acetaminophen toxicity
Abstract
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.
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Influence of a synthetic analogue of the active center of GM-CSF – peptide ZP2 on the growth and biofilm formation of gram-negative bacteria – causes of surgical infections
Abstract
The aim is to analyze the nature of the effect of the synthetic analogue of the active center of GM- CSF – peptide ZP2 on the growth and biofilm formation (BPO) of gram–negative bacteria – pathogens of surgical infections. The study used 18 clinical isolates of gram-negative bacteria of different species (Klebsiella pneumoniae, Citrobacter freundii, Stenotrophamonas maltophilia) isolated from purulent wounds in patients with surgical pathology and showing pronounced resistance to many antibiotics used in clinical practice. The isolation of pure cultures of microorganisms was carried out by conventional methods; species were assessed by direct protein profiling using a MALDI TOF mass spectrometer. To study the effect of ZP2 peptide on bacterial growth and BPO, isolates were co-cultured with a solution of ZP2 peptide in meat-peptone broth (MPB) at a concentration of 5 micrograms/ml at 37°C for 24-48 hours. The effect of the ZP2 peptide was studied both on emerging biofilms and on those formed, according to the degree of binding of crystalline violet in sterile 96-well polystyrene plates. Next, Growth inhibition indices and coefficients of BPO of microorganisms were determined. It was found that the synthetic analogue of the active center of granulocyte-macrophage colony stimulating factor (GM-CSF) – peptide ZP2 inhibited the growth of the studied bacterial strains, reducing the biomass of experimental cultures during the development of bacterial populations. At the same time, the species-specific effect of the ZP2 peptide on the ability of surgical strains of the studied bacteria to form biofilms has been shown. It was experimentally established that all the studied surgical strains of microorganisms were capable of biofilm formation, and the maximum severity of the trait was characteristic of S. maltophilia isolates. The synthetic analogue of the active center of granulocyte-macrophage colony stimulating factor (GM-CSF) – peptide ZP2 caused a decrease in the ability to form biofilms in isolates S. maltophilia and destroyed already formed biofilms in all studied species of microorganisms. The experimental data obtained expand the range of potential clinical applications of the synthetic analogue of the active center of granulocyte-macrophage colony stimulating factor (GM-CSF) – peptide ZP2, and its use in new medicines can be effective in combating antibiotic-resistant pathogens of surgical infections.
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Assessment of the influence of synthetic peptide of the active center of granulocyte-macrophagal colony-stimulating factor – ZP2 on the growth properties of Corynebacterium spp.
Abstract
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.
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Effect of tetrapeptides KK1 and KK5 on the immunological parameters of rat spleen during passive smoking
Abstract
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.
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Immunomodulatory properties of splenocytes treated with chlorpromazine in experimental aggression
Abstract
Aggressive behavior is considered to be as one of the central symptoms of many neuropsychiatric disorders. It is a serious medical and biological problem associated both with high frequency and severity of manifestations and lack of selective correction means. The purpose of this study was to evaluate the functional phenotype of immune cells treated with chlorpromazine in aggressive animals in vitro, as well as the effect of transplantation of these cells on syngeneic aggressive recipient’s immune cells functional activity. Aggressive behavior was formed in active mice as a result of repeated experience of victories in agonistic interactions with animals with a submissive partner. Further, aggressive animals were isolated into individual cells and used as donors and recipients of immune cells. Immune cells were obtained under sterile conditions from suspension of spleen cells precultured with chlorpromazine. The level of spontaneous and mitogen-induced cell proliferation was assessed using a standard method of radioactive label incorporation. The quantitative content of cytokines in samples of treated with chlorpromazine cell cultures supernatant was determined by enzyme immunoassay using appropriate test systems. Further aggressive syngeneic recipients were intravenously injected with splenocytes precultured with chlorpromazine. The control group of animals was injected with splenocytes precultured under similar conditions, without the chlorpromazine addition. The recipients were assessed for the spleen cells proliferative activity and the intensity of humoral and cellular immune response using standard methods, by the number of antibody-forming spleen cells and severity of a delayed-type hypersensitivity reaction in response to T-dependent antigen introduction. It was found that treatment with chlorpromazine in vitro suppressed mitogen-stimulated proliferation of splenocytes in aggressive mice, without changing of spontaneous proliferation. It was also accompanied by some cytokines production decrease: IL-6, IL-2 and IFNã. When studying the humoral and cellular immune response intensity in aggressive recipients after transplantation of donor’s syngeneic splenocytes treated with chlorpromazine, a decrease in the intensity of humoral immune response was recorded. Transplantation of donor’s splenocytes treated with chlorpromazine was also accompanied by a decrease in spontaneous and mitogen-stimulated proliferation of splenocytes from aggressive recipients. Thus, the obtained data indicate the inhibitory effect of chlorpromazine on immune cell’s functional activity in aggressive mice, as well as the positive immunomodulatory effect of chlorpromazine-treated immune cells transplantation at aggressive behavior in experimental animals.
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The effect of the immune response to SARS-CoV-2 S protein on angiotensin II levels in rats
Abstract
Autoantibodies against key molecules of the renin-angiotensin system (RAS) are found in some patients infected with SARS-CoV-2. These autoantibodies include antibodies against angiotensin II and angiotensin converting enzyme 2 (ACE2). The presence of antibodies to the RAS-related molecules is associated with episodes of hypotension or hypertension. The aim of this work was to study the effect of antibodies to SARS-CoV-2 S protein and autoantibodies to ACE2 on angiotensin II levels in a model of induced multiple organ damage caused in rats by immunization with SARS-CoV-2 S protein. The effect of pre-existing autoimmune encephalomyelitis on change in angiotensin II level caused by immunization with S protein is also was studied. Wistar rats were immunized with S protein of SARS-CoV-2 emulsified in incomplete Freund’s adjuvant (IFA). At the time of injection of S protein 6 of the rats were intact (S group), in 4 of the rat experimental autoimmune encephalomyelitis was previously induced by immunization with guinea pig myelin basic protein (EAE + S group). The control group of rats was injected with IFA. Antibodies to S protein, autoantibodies to ACE2, and angiotensin II level were determined in blood plasma by enzyme linked immunosorbent assay. It was found that immunization with S protein leads to a transient decrease in the blood level of angiotensin II. The blood angiotensin II level was lower than normal in 3 out of 6 rats (50%) in group S, and in 3 out of 4 (75%) in the EAE + S group at week 6 after immunization. The decrease in angiotensin II level was significant in the EAE + S group relative to the control group (ANOVA, p = 0.0423). A deeper decrease in the angiotensin II level in the blood of EAE + S group than in S group was associated with a higher level of antibodies to S protein: the level of antibodies to S protein was significantly higher in the EAE + S group for 1-6 weeks after immunization with S protein compared to the S group of rats. Immunization of rats with S protein did not cause the production of anti-ACE2 autoantibodies in the EAE + S group, and in the S group it was weak and was not accompanied by an increase in angiotensin II levels. Thus, in rats immunized with S protein, a transient decrease in the level of angiotensin II was detected at the peak of production of antibodies to S protein, which may indicate that antibodies to S protein may contribute to a decrease in angiotensin II level in SARS-CoV-2 infection. In addition, pre-existing autoimmune disease leads to a stronger response to S protein, accompanied by a stronger decrease in angiotensin II level.
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Histological analysis of the spleen of rats immunized with SARS-CoV-2 S protein
Abstract
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.
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Leukocyte indices in dogs with acquired primary hypothyroidism
Abstract
According to global statistics, hypothyroidism in dogs is a widespread disease. However, due to certain difficulties in conducting laboratory diagnostics, as well as the cross-species specificity of such indicators as thyroid-stimulating hormone, thyroglobulin autoantibodies, prompt diagnosis and differentiation of hypothyroidism in dogs in the practice of a veterinarian is difficult. Thus, it is relevant to search for secondary auxiliary methods of diagnosis and detection of hypothyroidism in dogs based on a set of indicators and diagnostic coefficients-indices. Since hypothyroidism causes an immune system malfunction, such indicators may be leukocyte indices characterizing indicators of nonspecific cellular immunity and the organism reactivity.
The purpose of the presented study was to evaluate the leukocyte indices of dogs with primary acquired hypothyroidism for further use in order to facilitate the diagnosis of thyroid dysfunction in dogs, as well as to study the formation of an immune response in different animal species, followed by its possible use in experimental studies of the influence of various factors on the nonspecific cellular immunity of animals and humans.
The blood leukogram parameters of 15 dogs with established primary hypothyroidism were evaluated before the start of replacement therapy and compared with similar leukogram parameters of clinically healthy dogs (n = 19).
There was a significant increase in the leukocyte intoxication index (p ≤ 0.05), the leukocyte shift index (p ≤ 0.1), the nuclear index of G. D. Dashtayants (p ≤ 0.05) in the group of hypothyroid dogs compared with the group of healthy dogs (n = 19).
An increase in the leukocyte intoxication index may indicate the development of inflammatory processes and an increase in the degree of endogenous intoxication of the body. An increase in shift index in the blood of sick dogs may indicate active inflammatory processes, as well as a decrease in the degree of immunological reactivity in hypothyroidism. The increase of nuclear index of G. D. Dashtayants characterizes an elevation in the rate of regeneration of neutrophils and monocytes and an increase in the duration of circulation of these types of leukocytes in the bloodstream. This, in turn, indicates a chronic process. Thus, when detecting a simultaneous increase in the blood of a dog of such leukocyte indices as mentioned above, attention should be paid and included in the list of possible differential or concomitant diagnoses of hypothyroidism. In the future, the study is planned to expand with an increase in the sample of animals, record and analysis of individual physiological conditions and breed characteristics, as well as dietary characteristics, correlation with the severity of the condition, analysis of life expectancy and survival.
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Co-cultivation of mastocytes and cumulus cells in polycystic ovary syndrome
Abstract
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 1st, 3rd, and 7th 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 7th 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 7th 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.
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The influence of a composition based on exometabolites of Saccharomyces boulardii in relation to the pathogenic and persistent properties of fungi of the genus Candida
Abstract
Clinical manifestations of mycoses vary widely from mild mucosal damage to severe invasive forms. Currently, the pharmaceutical market offers a wide range of antimycotic drugs, including oral and injectable drugs for systemic and external and local use. Varying degrees of effectiveness are due to the chemical structure and pharmacokinetics. A significant problem is the recurrence of mucosal candidiasis. One of the possible solutions to this problem can be considered the use of exometabolites of bacterial or fungal origin, affecting the morphofunctional structures of fungi of the genus Candida spp. The purpose of the study was to obtain cell-free supernatant of Saccharomyces boulardii (S. boulardii) and herbal extracts, which are the basis of a composition with a preventive effect against fungi of the genus Candida. The authors proposed a composition based on the exometabolite of S. boulardii and herbal extracts for the prevention of candidiasis. Propylene glycol served as a control. The effectiveness of the composition was assessed on clinical isolates of C. albicans, C. glabrata and C. krusei isolated from the vaginal biotope at a dilution of 103-106 CFU/mL. At the first stage, we studied the effect of S. boulardii metabolites on the biological properties of fungi. Next, the fungicidal activity of metabolites and extracts was determined by serial dilution against micromycete isolates. At the final stage, the effect of the composition with the most effective extracts was studied. Under the influence of the supernatant of S. boulardii, micromycetes lost the ability to form growth tubes, and a decrease in the catalase activity of Candida spp. was observed both during carriage and disease. Exometabolites significantly reduced the ability to form film in cultures isolated from patients with vaginal candidiasis. The most effective among the extracts were the extracts of St. John’s wort and coriander. The fungicidal properties of the composition were maintained for 12 hours after co-incubation with all isolates of Candida spp. Thus, the composition is effective against both C. albicans and C. non-albicans carriage and disease.
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Modeling the processes of transendothelial transport of LDL and macrophage migration
Abstract
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.
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Determination of antinuclear antibodies: role in modern differential diagnosis of connective tissue autoimmune diseases
Abstract
There is an increase in autoimmune rheumatic diseases among all age population groups globally. Diagnosis is often difficult, because the early stages of the diseases usually do not have specific symptoms. Often, clinical manifestations of autoimmune diseases and non-autoimmune pathologies have similar symptoms. Therefore, the differential diagnosis could be very difficult. Most often, the determination of antinuclear autoantibodies is used for laboratory diagnosis of connective tissue systemic diseases. Autoantibodies can be detected in patients long time before the appearance of symptoms. The correct diagnosis is very important because the therapy of various nosologies can be different. It is especially significant with the invention of targeted therapy. Further analysis of the diagnostic value of autoantibody determination is very important. This article presents examination and follow-up data of three children. The analysis of medical documentation was carried out. The role of determining autoantibodies in the differential diagnosis of autoimmune connective tissue diseases was analyzed. In the first patient with Sjögren’s syndrome, the clinical picture of the underlying disease developed at least 5 years after the detection of high levels anti-SS-A, SS-B and Ro-52 antibodies (immunoblotting) and the speckled pattern (indirect immunofluorescence assay). In the second patient, antibodies against centromeres (specific markers of systemic scleroderma) appeared at least 2 years before clinical symptoms. In the third patient, the specific markers of systemic scleroderma have been detected for 5 years. There were antibodies against centromeres (immunoblotting), high titer and the centromere pattern (indirect immunofluorescence assay). However, the patient has not developed any clinical symptoms of this disease during all time of observation. Thus, the analysis of the presented clinical cases shows that autoantibodies can be detected in patients long time before the onset of clinical manifestations of a specific autoimmune disease. In all three cases, the first immunological examination has been carried out in the background of the disease symptoms, but they were atypical. Identification of specific autoantibodies, is very important for differential diagnosis. In the absence of clinical symptoms, the presence of autoantibodies, is the reason for dynamic observation of the patients.
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Features of diagnostics and therapy of familial Mediterranean fever
Abstract
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.
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Single nucleotide polymorphism of IL-17F as a possible biomarker of rheumatoid arthritis in the Russian population of the Chelyabinsk Region and its non-equilium linkage with IL-17A
Abstract
The interleukin 17 (IL-17) family and its role in the immune response and various pathologies is studied in different research. IL-17A and IL-17F belong to proinflammatory cytokines and are the most studied members of the interleukin 17 family and have similar functions and the greatest activity. They play a key role in the immune response in autoimmune diseases, including rheumatoid arthritis. The key point in the regulation of the amount and functional activity of cytokines, including IL-17A and IL-17F, is polymorphism of their genes. Due to the fact that the polymorphism of the IL-17F gene 7488 T/C is located on chromosome 6 near the polymorphism of the IL-17A gene -197G/A and they both take part in the immunopathogenesis of RA, it is possible that their allelic variants are inherited linked and form haplotypes. The purpose of our study is to identify a possible association of IL-17F gene polymorphism with a predisposition to rheumatoid arthritis, including depending on the age and gender of patients in the Russian population of the Chelyabinsk region, as well as to assess the formation of IL-17A ~ IL-17F haplotypes in a group of patients in comparison with a group of conditionally healthy individuals. The result of our study reliably indicates that the homozygous genotype for the ancestral allele 7488 TT of the IL-17F gene (p << 0.001) makes a huge contribution to the susceptibility to rheumatoid arthritis, including in the group of men. In addition, polymorphisms in the IL-17A and IL-17F genes are linked to each other and form two haplotypes. One of them, IL-17A -197*G ~ IL-17F 7488*C, is associated with a reduced risk of developing rheumatoid arthritis. This haplotype is formed by the ancestral allele of the IL-17A gene and the mutant allele of the IL-17F gene, which takes over the main function and reduces the protein activity level and probably thereby reduces the risk of developing RA.
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Association between sialic acid, sialidase activity and cholesterol of lipid-containing circulating immune complexes in the blood serum of patients with atherosclerosis
Abstract
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.
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Clinical and pathogenetic significance of the phenomenon of functional heterogeneity of oxygen-dependent functions of neutrophils in ankylosing spondylitis
Abstract
Neutrophils are able to exert a variety of effects on other cells of the immune system, which indicates their heterogeneity. In various rheumatic diseases, neutrophils are involved in the immunopathological process. The study of the phenomenon of functional heterogeneity of neutrophils associated with the pathogenesis of rheumatic diseases is a promising area of research in immunology and rheumatology. The purpose of the research: study of factors influencing oxygen-dependent neutrophil functions in ankylosing spondylitis (AS). A total of 82 patients with AS were examined. The functional activity of neutrophils was assessed according to the data of determining the indicators of oxygen-dependent functions by the chemiluminescence method. Functional neutrophil reserve (FNR) was assessed by activation coefficients (the ratio of chemiluminescence induced by suspension of heat-killed staphylococcus cells to spontaneous value). Statistical data processing was carried out using Statistica 10.0 program.
An increase in oxygen-dependent neutrophil functions in AS was accompanied by an increase in disease activity. The greatest influence on the increase in the functional activity of cells was exerted by the age of patients, the stage of the disease and the level of circulating immune complexes. The process of stabilizing the metabolic activity of neutrophils was significantly influenced by the age of patients, ESR, ã-globulins, total cholesterol, and low-density lipoprotein cholesterol. Among the laboratory parameters, the majority of AS patients with moderate and high FNR had elevated levels of ESR, CRP, and IgM; there was a tendency to increase IgA in AS patients with high FNR. Statistical analyses showed an association between FNR and disease activity; there was no statistically significant dependence of FNR on the stage, course, and form of AS. The study of the metabolic activity of neutrophils during dynamic observation revealed a group of patients with stabilization of FNR parameters against the background of therapy with the achievement of a normal level of oxygen-dependent metabolism. Thus, in ankylosing spondylitis, the functional heterogeneity of neutrophils associated with disease activity was established according to the determination of oxygen-dependent metabolism.
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WNT signaling pathway and its connection with metabolic disorders: The role of DVL-1 and WIF-1
Abstract
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.
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The expression patterns of the inhibitory receptors PD-1 and TIGIT on CD4+ and CD8+T lymphocytes at different stages of differentiation
Abstract
T lymphocytes are a highly diverse group of cells that play a pivotal role in the adaptive immune response. The T cell population consists of two subsets: CD4+T-helper cells and CD8+ cytotoxic T lymphocytes, each comprising cells with varying functionality and maturity levels. Inhibitory receptors such as PD-1 and TIGIT tightly regulate T lymphocyte functions to maintain immune homeostasis. However, the presence of inhibitory receptors on T cells is also associated with exhaustion. The specific characteristics of inhibitory receptor expression on CD4+ and CD8+T lymphocyte subsets are not fully understood. This study aimed to assess the expression of inhibitory receptors PD-1 and TIGIT on different subsets of CD4+ and CD8+T lymphocytes in healthy individuals. The study involved 10 relatively healthy volunteers, averaging 43 years. T lymphocytes subsets were identified using flow cytometry. CD4+ and CD8+T cells were classified as naive (CD45R0-CCR7+), central memory (CD45R0+CCR7+), effector memory (CD45R0+CCR7-), or terminally differentiated effectors (CD45R0-CCR7-) followed by analysis of PD-1 and TIGIT expression. The study showed that the expression of suppressor molecules PD-1 and TIGIT on T lymphocytes in healthy individuals is closely linked to their differentiation stage. The presence of cells carrying PD-1 and TIGIT receptors was significantly lower in naive T lymphocytes compared to more mature subsets (p < 0.05). Affiliation with CD4+ or CD8+T cells also significantly influenced the nature of inhibitory receptor expression. CD8+T lymphocytes had more TIGIT-positive elements than CD4+T cells (p < 0.01). Moreover, unlike PD-1, TIGIT was found on most memory and terminally differentiated effector CD8+T lymphocytes. These findings improve our understanding of how inhibitory receptors regulate T cell functions and emphasize the need to reconsider how we interpret data in the context of T lymphocyte exhaustion.
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Study of the phagocytic activity of neutrophilic granulocytes in the peripheral blood of residents of Abkhazia of different ages
Abstract
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.
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Clinical and epidemiological aspects of primary immunodeficiencies in the Republic of Karakalpakstan
Abstract
Studying the prevalence of primary immunodeficiency disorders (PID) is an important aspect of epidemiological research, as it allows for assessing the frequency of these diseases occurring in different regions. The distribution of PID may vary depending on ethnic background and geographical location. Information on the prevalence of PID at regional, national, and international levels enables a more accurate determination of the scale of the problem and the development of effective prevention and treatment strategies. Studying the epidemiological and clinical profile of congenital immune disorders (PID) in the Republic of Karakalpakstan is crucial for understanding the prevalence, age and gender structure, as well as the spectrum of nosological forms of these rare diseases. The aim of this study was to investigate the epidemiological and clinical characteristics of congenital immune disorders, primary immunodeficiencies in the Republic of Karakalpakstan. The study material consisted of data on patients receiving inpatient treatment at a multidisciplinary children’s hospital in the Republic of Karakalpakstan and those under the care of an allergist-immunologist in the outpatient clinic at district medical centers in the Republic of Karakalpakstan. The average delay in diagnosis from the onset of clinical manifestation of PID in the region was 2.7 years. It was found that the mortality rate was 2.8%. Screening tests for verifying PID in the diagnostic search stage included clinical and biochemical blood analyses, and determination of serum immunoglobulins. At the time of diagnosis, patients exhibited a significant decrease in IgG and IgA immunoglobulin levels. In addition to the disorder in the humoral branch of adaptive immunity, children with this disease showed a decrease in the absolute number of T lymphocytes. The data obtained from the study indicate insufficient diagnosis of primary immunodeficiencies in the Republic of Karakalpakstan, which may serve as a basis for the development of educational programs aimed at increasing awareness of primary immunodeficiencies. Further research and systematization of information on patients with primary immunodeficiencies are necessary for the development of regional programs for the implementation of screening diagnostics.
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Immune status of students with different levels of physical activity
Abstract
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.
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Immunogram dynamics of students under the influence of dosed physical activity
Abstract
Analysis of the dynamics of the state of blood leukocytes in muscular activity is relevant due to the development of methods of differentiation and assessment of the state of these cells. The purpose of the study is to study the dynamics of the phagocytic and NBT activity of neutrophils, as well as the content of CD lymphocytes of peripheral blood in students when moving on a treadmill. For students 18-20 years old involved in athletics (3 boys and 4 girls), blood was taken from the ulnar vein before and after a 15-minute jog, as well as after a 15-minute run of moderate intensity. The average level of physical performance of the examined PWC170 was 16.25±2.21 kGm/min/kg. Assessment of phagocytosis and NBT activity of neutrophils and determination of blood CD lymphocytes by immunophenotyping were performed using flow cytometry. It was found that in girls at rest, the relative content of lymphocytes and NK cells was significantly lower, and the level of induced NBT activity of neutrophils and the relative content of CD4-CD8- and CD4+CD8+ lymphocytes was significantly higher than in boys. At the same time, the dynamics of the leukogram parameters examined during the dosed physical activity fully corresponded to the development of the lymphocytic phase of myogenic leukocytosis. With an increase in the power of repeated exercise against the background of a general increase in the number of phagocytic neutrophils, the balance of spontaneous NBT-positive and reserve potentially active neutrophils significantly increased relative to the content of NBT-negative cells in the induced test. At the same time, the level of neutrocytes in girls was significantly higher, causing a higher level of phagocyte count and absolute content of NBT-positive neutrophils in a spontaneous and induced test. At the same time, against the background of an increase in the absolute content of CD4-CD8- and TNK lymphocytes, a statistically significant increase in the relative and absolute content of NK cells was observed. In contrast to the boys after the 2nd physical exercise, the relative and absolute content of NK cells, as well as the increase in the percentage of HBT-positive cells in the induced test, were significantly higher.
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Phenotypic heterogeneity of the B lymphocyte population in the context of post-traumatic stress disorder in veterans of modern wars
Abstract
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.
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The involvement of proinflammatory cytokines in the pathogenesis of audiogenic epilepsy
Abstract
Epilepsy is a heterogeneous disease, which determines the relevance of investigating the mechanisms of pathogenesis of its various types, including reflex epilepsy. Pharmacotherapy is common for the treatment of patients with epilepsy, however, despite the significant recent achievements, 20-30% of patients remain resistant to the ongoing treatment. The urgency of creating new antiepileptic drugs, in particular, immune ones is due not only to a significant proportion of pharmacoresistant cases, but also to the struggle for the quality of life of patients. The neuroinflammation system in animals with different genetically determined audiogenic epilepsy proneness was investigated. These genetic groups were Krushinsky–Molodkina rats (tonic seizures of maximum intensity in response to the action of sound) and “0” strain (control group, non-convulsive phenotype). The main proinflammatory cytokines levels in the dorsal striatum and brain stem in rats of these genetic groups were measured by multiplex immunofluorescence assay. Background levels of IL-1â, IL-6 and TNFá in the dorsal striatum of KM rats were significantly lower than in the control “0” strain rats, whereas in the brain stem in the “background” levels of these metabolites did not differ. Four hours after the sound exposure, the TNFá level in the dorsal striatum of KM rats was significantly lower than in “0” rats. In KM rats, after the sound exposure and subsequent tonic seizures, the levels of IL-1â and IL-6 in the dorsal striatum were significantly higher than in the background. The IL-2 content was not detected in the background in KM rats, whereas after audiogenic seizures its level was 14.01 pg/ml. In the brain stem of KM rats, the levels of IL-1â and TNFá after audiogenic seizures were significantly lower than in the background. In rats of the “0” strain, cytokine levels in the dorsal striatum after the sound exposure did not differ from those in the background, while IL-1ß levels in their brain stem were significantly lower than the background state. Particular modulating role of the studied proinflammatory cytokines in the pathogenesis of audiogenic epilepsy is assumed, as well as certain possibility of anti-inflammatory and immune drugs application in anticonvulsant and antiepileptic therapy.
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Immune factors associated with prominent negative symptoms and disease severity in schizophrenia
Abstract
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.
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Severity of traumatic brain injury governs alterations in type 17 T helper cell subset composition
Abstract
Immune cell hyperactivation along with cytokines they overproduce plays an important role in traumatic brain injury (TBI). A central place in the immunopathogenesis of TBI is held by diverse cell-mediated reactions governed by T helper (Th) cell populations including Th17 subset. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 123): group 1 – patients with concussion; group 2 – mild TBI; group 3 – moderate TBI; and group 4 – severe TBI. The control group was samples from healthy volunteers (n = 48). T cell subset composition was assessed by flow cytometry. Within Th central memory cells (Th CM): the level of “double-negative” Th17 (DN Th17) was significantly increased in patients with mild TBI (p = 0.014) and moderate TBI (p = 0.003); the level of “classical” Th17 (p = 0.010) also was significantly increased, but only with severe TBI; the level of “non-classical” Th 17 (Th17.1) were shown to have significantly reduced level only patients with severe TBI (p = 0.008); the level of “double-positive” Th17 (DP Th17) was significantly increased in patients with mild TBI (p = 0.006) and moderate TBI (p = 0.012). Within Th effector memory cells, an increased level of DN Th17 turned out to be significantly increased in all groups (p < 0.05) and “classical” Th17 in patients with mild TBI and moderate TBI (р < 0,05); the level of Th17.1 was significantly reduced in patients with severe TBI (p = 0.015). The results indicate the active generation of a subpopulation of Th17 cells of both central (Th CM) and effector memory (ThEM), which indicates directed migration of cells in response to TBI. This probably occurs due to the high plasticity of Th17 (changes in phenotype) and functional properties that change depending on the microenvironment into which a particular cell finds itself, which causes the occurrence of reciprocal changes as a response to damage in nervous tissue of different severity.
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Markers of systemic inflammation in hemorrhagic stroke with effective and ineffective cerebral blood flow
Abstract
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.
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Protective role of hypoxia-induced factor-1α and HIF-1A gene polymorphism in the development of acute pancreatitis
Abstract
Acute pancreatitis (AP) is an acute surgical disease of the abdominal cavity that becomes severe in 20-30% of patients and has a mortality rate reaching 25%. Hypoxia that occurs during AP may be associated with the activation of a regulatory protein, hypoxia-inducible factor-1á (HIF-1á), which plays an important role in the body’s response to hypoxia. The HIF-1 transcription factor induces the expression of genes involved in cell proliferation, angiogenesis, neurogenesis, erythropoiesis and cellular metabolism, and maintenance of intracellular pH. The purpose of the work is to study the relationship between HIF-1á blood levels and polymorphism of the HIF-1A gene with the criteria of hypoxia, tissue damage and severity of AP. We examined 93 patients with AP of varying severity on days 1 and 3 of the disease, age 48 (39-67) years. We identified 3 groups of patients: with mild AP – 32 people, moderate – 26 people, or severe – 35 people. The comparison group consisted of 25 healthy volunteers, average age 47 (39-56) years. The HIF-1á levels, the presence of HIF-1A gene polymorphism, interleukin-6, C-reactive protein, procalcitonin, ferritin, D-dimer, S100 protein, clinical blood test, and blood gas composition were assessed. In patients with AP, clinical and laboratory signs of acute inflammation, microcirculation disorders, hypoxia and organ dysfunction were observed. With mild severity of AP on days 1-3 of observation, the HIF-1á level exceeded its content in the comparison group. With moderate and severe AP, the production of HIF-1á as a factor of adaptation to hypoxia decreased. A relationship was found between the HIF-1á level and the severity of AP. In the same patients, the HIF-1A gene polymorphism (1772C>T, rs11549465) was studied to identify carriage of the C/C, C/T and T/T genotypes. It was determined that among the patients, patients with С/С predominated, in whom the concentration of HIF-1á was lower than in the group with С/T. Mortality among patients with the C/C genotype and severe AP was 47%. In the group with the C/T genotype, all patients were discharged, including those with severe AP. A relationship was found between HIF-1á blood levels and the marker of tissue damage S100, mixed hypoxia – lactate, and acid-base state – pHt. The results allow us to consider HIF-1A genotypes as potential predictors of the severity of AP.
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Immunity in chronic rhinosinusitis and comorbid conditions
Abstract
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.
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Allergy mapping in children with allergic rhinitis in different subjects of the Russian Federation
Abstract
Given the climatic and geographical location and differences in the change of seasons in the Russian Federation, there is a marked heterogeneity in the representation of respiratory allergens. Obviously, in the case of double or triple sensitization, the diagnosis of its true picture is a difficult task. In such cases, allergy-component analysis is an extremely necessary stage of allergological examination. Purpose of the study: to assess the sensitization spectrum of AR patients in the age group from 3 to 17 years inclusive, living in different regions of the Russian Federation. Comparative analysis of differences in the sensitization spectrum of AR patients in the Republic of Ingushetia in different age groups.
The study involved 47 patients, 36 of them were children under 18 years of age: Moscow n = 9 (Central Federal District), Samara n = 8 (Volga Federal District), Magas n = 19 (North Caucasus Federal District, Republic of Ingushetia). Also, 11 patients aged 18 years and older from Magas city took part in the study. The results obtained by ImmunoCAP ISAC and ALEX2 immune solid-phase allergy test were analyzed. The numerical values of the main respiratory allergens were evaluated, in patients with clinical signs of AR in the period from 01.01.2023 to 27.01.2024. The diagnosis of AR was made according to generally accepted criteria for diagnosis.
The main causative factor of AR formation is the major allergen of birch pollen (Bet v1). However, for the Central Federal District, heterogeneity of representation in the group of buciferous trees was noted, which should be taken into account when planning allergen-specific immunotherapy. The spectrum of sensitization of children with AR in the North Caucasian Federal District (Magas) differs significantly from the Central and Volga Federal Districts, where the main major allergen of Amb a 1 ragweed pollen forms the etiological basis of AR formation. When comparing patients with AR of different age groups from Magas city, no differences in the sensitization spectrum were found.
The results indicate a high degree of importance of allergy-component diagnostics to improve the effectiveness of allergen-specific immunotherapy.
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The value of objective methods for assessing nasal breathing function in the diagnostic algorithm for allergic rhinitis
Abstract
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.
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Clinical factors as predictors of the development of severe recurrence of chronic spontaneous urticaria after completion of omalizumab therapy
Abstract
Chronic spontaneous urticaria (CSU) affects about 1% of population, and its prevalence is increasing. The disease occurs in both children and adults, with predominance among women. At least two possible causes of CSU have been identified, two autoimmune endotypes, with different types of autoantibodies associated with activation of skin mast cells. In clinical practice, patients with CSU receive therapy accordance the clinical recommendations of the Ministry of Health of Russia for treatment of urticaria, according to the doctor’s algorithm of actions. In patients with CSU, symptoms are difficult to relieve due to special mechanisms of development this variant of disease. In recent years, specific markers, including clinical and laboratory parameters, have been described that can predict response to treatment patients with CSU. In clinical practice, we encounter difficulties in managing these patients. One of these is recurrence of urticaria symptoms after cessation of omalizumab treatment, which negatively affects compliance of patients and its psycho-emotional background. A retrospective analysis of 14 patients with CSU with resumption symptoms after completion of omalizumab treatment was carried out. Patients were divided into two groups: 1 group – 10 patients that symptoms began controlled with antihistamines (go to 1st therapy stage); and 2 group – 4 patients who need re-prescription of omalizumab (stay on 3rd treatment stage). The duration of CSU, activity according to UAS7, combination with development of angioedema, presence of concomitant allergic and autoimmune pathologies, level of CRP, total IgE, and presence of TPO antibodies were analyzed. There was no tendency relapses severity CSU after omalizumab discontinuation with age, gender, duration of the disease, presence of concomitant allergic diseases and drug hypersensitivity. In patients with high disease activity was tendency toward more severe relapses of CSU. The search and study of predictors response to treatment of CSC remains actual task. Further research to identify predictors of response to treatment and relapses severity help identify groups of patients for early transition to more effective treatment methods, which optimize and personalize management of patients with CSU.
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Validity of medical exemptions from vaccination in persons with allergic disorders
Abstract
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.
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Changes in the levels of cytokines IL-1β, IL-4, IL-8, and IL-10 in dental orthopedic fixed prosthetics
Abstract
Despite significant advances in materials science, introduction of new methods and principles of prosthetic treatment into the practice of dentists, complications after prosthetics with fixed structures are encountered. The result of dental prosthetics of patients with defects of hard tissues of teeth depends not only on the chosen construction and materials from which they are made, but is closely connected with the functional activity of the immune system. Cytokines are an important factor of mucosal immunity. The cytokine system represents one of the key components of mucosal immunity. It regulates normal physiological functions, restoration of haemostasis in the interaction of physical, chemical and biological factors on the body and participates in the pathogenesis of allergic, autoimmune, and autoinflammatory processes. The aim of the study is to compare the content of IL-1â, IL-8, IL-10, and IL-4 in unstimulated saliva and gingival fluid in patients during adaptation to metal-ceramic and oxide ceramic tooth-supported constructions. In the period from 2021-2024, we examined 3 groups of patients aged 46±2 years: group 1 – comparison group, patients without dental constructions in the oral cavity (25 people); group 2 – patients treated with tooth-supported metal-ceramic (MC) crowns (25 people); and group 3 – patients treated with tooth-supported zirconium dioxide (ZrO2) crowns (25 people). On the basis of IL-1â, IL-8, IL-10, and IL-4 we concluded that the mucosal immunity of oral mucous membranes is less affected by the structures made of oxide ceramics compared to the crowns made of metal-ceramics. Similar patterns of changes in the levels of IL-1â, IL-8, and IL-4 in saliva and gingival fluid in patients who underwent dental rehabilitation were found, which allows us to use only saliva in order to eliminate the complexity and specificity of gingival fluid sampling. Also, changes in cytokine indices in saliva and gingival fluid at different stages of prosthodontics reflect the level of reaction of oral mucosal immunity, which can serve as a criterion of the quality of the performed dental treatment.
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CD14 gene polymorphism in COVID-19 convalescents: analysis of (C-159)T
Abstract
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).
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Clinical and immunological characteristics of post-covid patients with infectious immunopathology syndrome
Abstract
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has caused global morbidity and high mortality worldwide. Today it is known that, despite recovery from COVID-19, confirmed by both laboratory and instrumental diagnostic methods, many patients, regardless of the severity of the disease, suffer from a significant deterioration in health and increased exacerbations of chronic diseases. During examinations by attending physicians, they note fatigue, an increase in cases of acute respiratory viral infections per year, an increase in relapses of skin diseases such as furunculosis, pyoderma, exacerbation of pulmonary pathologies, pathologies of the urinary tract of inflammatory origin, as well as chronic infectious diseases such as herpesvirus and human papillomavirus infections, which occur for the first time or are characterized by frequent relapses no less than six months after recovery from acute COVID-19. Such persistent post-infectious consequences are known as post-COVID syndrome. SARS-CoV-2 infection is accompanied by damage to both the acquired and innate immune systems. In previous work, we determined the role of B cells, cytotoxic T lymphocytes, natural killer cells and the regulatory properties of CD46, as well as its involvement in the processes of viral entry into the cell. In this study, we studied the relationship of immune disorders of these factors of innate and acquired immunity with the clinical manifestations of post-COVID infectious syndrome in this category of patients and the severity of lung damage in these patients during the acute period of COVID-19. The results of the study showed that in some patients more than six months after suffering from COVID-19, the following was revealed: in patients who had a coronavirus infection without lung damage, no violations of the innate and acquired parts of the immune system were detected. In addition, significant differences were identified between clinical manifestations of diseases with increasing cases of relapses or newly identified after clinical recovery from an acute COVID-19 infection, depending on the phenotype of immune status disorders.
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Assessment of immune status markers during occupational lead exposure
Abstract
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.
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Clinical and immunological efficacy of complex therapy for bronchial asthma in children with the inclusion of components of far eastern brown algae
Abstract
Classical basic therapy for asthma is aimed at stopping inflammation, primarily atopic, and has achieved significant positive results in the treatment of the disease, which has led to a decrease in the severity of asthma. The proportion of patients in whom asthma control is achieved does not exceed 30%; complete control is achieved in 5%, that is associated with the influence non-atopic factors on the pathogenesis of BA, leading to the search for additional methods of correction. Despite the identified biological, immunomodulatory properties of the components of brown algae, the mechanisms of their action, in asthma, are not sufficiently illuminated, which became the purpose of this study: to determine the possible immunomodulatory effect of a functional food product in children with asthma based on brown algae (Far Eastern kelp) and its use in addition to standard therapy to improve control of the course of this disease. Children with asthma (n = 56) aged from 5 to 17 years were comprehensively examined and divided into 2 groups: those who received a functional food product in addition to standard therapy (n = 20) and those who received only standard therapy (n = 36). Laboratory tests included CBC, immunogram, cytokines (IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL- 10, IL-18, TNFá), blood ICC MPM, and herpesvirus DNA. Against the background of complex treatment, changes in the interleukin profile (IL-6, IL-10, IL-18) were noted, characteristic of a decrease in the intensity of inflammatory processes, including nonspecific ones, expressed in a tendency towards a decrease in the total number of lymphocytes, an increase in the immunoregulatory index both due to an increase in the number of T helper cells and and reduction of killer T cells. This was confirmed by a decrease in monocytes and ESR. Improved energy supply of immunocompetent blood cells (granulocytes and monocytes), a decrease in the number of patients with active replication of EBV and herpes virus type 6 indicate its immunomodulatory effect. The result of these changes was the positive clinical dynamics of asthma control indicators, which allows us to recommend the inclusion of a functional food product based on Far Eastern brown algae in addition to standard therapy for children with asthma aged 5-17 years.
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The role of immune factors in the development of preterm birth
Abstract
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.
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Effect of highly-active antiretroviral therapy on neuroendocrine regulation of immunogenesis in HIV-infected children
Abstract
Comparative assay has been made against the parameters of the immune and endocrine systems in 84 HIV-infected children born from HIV-infected mothers. One group of analyzed children (36 patients) did not receive highly-active antiretroviral therapy. Another group (48 patients) received different variants of highly-active antiretroviral therapy. Children aged from 1 to 182 months were examined. Venous blood samples taken from young patients were used to determine leukocyte blood composition considering the relative (%) and absolute number of blood cell counts. Hormone concentration was determined concurrently. CD-molecule expression by mononuclear cells was registered using flow cytofluorimeter. Plasma viral load in HIV-infected children was quantitatively detected with RT-PCR. Statistically significant lowering in the levels of free thyroxin, cortisol and progesterone was observed in children against a background of highly-active antiretroviral therapy as compared to those without HAART use. Correlation assay between the hormone level and the immunological parameters in children not receiving the antiretroviral preparations revealed marked positive correlations among the somatotropic hormone level and CD3+, CD4+ and CD8+ absolute numbers. Similar positive correlation with absolute T-subset number was found against free T4. The progesterone level also positively correlated with relative CD3+ and CD8+ numbers and showed negative correlation with absolute CD4+ amount. There is another positive correlation with relative T-subset number against the dehydroepiandrosterone level in the group of children without antiretroviral preparation therapy. As for HIV-infected group of children, against a background of highly-active antiretroviral therapy, the results of correlation assay between the hormone concentrations and cell parameters were found to significantly vary. There were observed positive correlations between the levels of cortisol and CD3+ (%), cortisol and CD8+ (%), estradiol and CD4/CD8, progesterone and absolute CD8+ number. As with children not receiving the antiretroviral preparations marked positive relation was revealed between the concentration of free thyroxin and absolute values of CD4+. Negative correlations were recorded between the estradiol level and the relative CD3+ numbers. Against a background of applying the antiretroviral preparations the correlation assay conducted between the viral RNA concentration (lg of copy number of mRNA/ml) and analyzed endocrinological parameters was found to have marked positive correlation with HIV concentration demonstrated by estradiol and testosterone. During the antiretroviral therapy, however, the negative correlation between the thyrotropin level and lg concentration of viral RNA was observed. Analytical results of correlation among the viral RNA concentration (lg copy number of mRNA/ml) and analyzed immunological parameters in this group of children evidence for specific ‘normalization’ due to highly-active antiretroviral therapy as the only positive correlation with virus concentration was detected for CD4+T subsets.
Therefore, the alteration in endocrine system state in children born from HIV-infected mothers could be of great significance while monitoring the systemic regulation of the immunogenesis.
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