Vol 27, No 4 (2024)

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SHORT COMMUNICATIONS

Methodological approaches to the comparative assessment of cellular reactions of innate immunity in mollusk Pomacea sp. (Caenogastropoda, Ampullariidae) in experimental aseptic inflammation

Khrushchev K.A., Shilov S.Y., Barkov S.Y., Shilov Y.I.

Abstract

One of the significant methodological problems that arise in the study of cells of the innate immunity of invertebrates is the unsuitability of culture media and even salt solutions intended for mammals and humans. Another important methodological point is the significantly pronounced reactions of coagulation, which play an important protective role in all invertebrates, but manifest themselves in vitro in cellular suspensions prepared even with optimal saline solutions for this animal. To solve this problem, researchers widely use an anticoagulation buffer with ethylenediaminetetraacetic acid (EDTA) even in functional tests. From the standpoint of traditional approaches of mammalian immunology, the use of EDTA is possible only for the study of cell morphology, but not their functions. The aim of the work is to adapt methodological approaches to the comparative assessment of cellular reactions of innate immunity in Pomacea sp mollusks in experimental aseptic inflammation. To evaluate the functions of phagocytic cells in mollusk Pomacea sp., we used a complete salt solution (CSS) with optimal concentrations of glucose, calcium ions, magnesium with addition to prevent coagulation, cellular aggregation and degranulation instead of EDTA sodium salt of heparin at a concentration of 100 IU/mL (CSS-hep). As a result of a specially conducted experiment, it was shown that during incubation of hemolymph cells in this solution, their viability is preserved, evaluated by flow laser cytometry during incubation with annexin V-PE (PE Annexin V) and 7-aminoactinomycin D (7- AAD), as well as in a test with trypan blue. The possibility of studying the phagocytic activity and a phagosome acidification of leukocytes from hemolymph, hematopoiesis organ (kidney) and the focus of inflammation induced by intramuscular injection of sterile suspension of zymosan using CSS-hep is shown. Unlike the Limnaea stagnalis and Biomphalaria glabrata mollusks, in which the production of reactive oxygen species by phagocytes in the luminol-dependent chemiluminescence reaction is well documented, we were unable to induce this reaction in Pomacea sp. mollusks. In a specially conducted experiment, we did not reveal the effect of the sodium salt of heparin at a concentration of 100 IU/mL on the production of reactive oxygen species by rat phagocytes.

Russian Journal of Immunology. 2024;27(4):749-756
pages 749-756 views

Physical-information model of the immune system as a development of P.K. Anokhin’s theory of functional systems

Moiseev V.I., Mochalov K.S., Goloviznin M.V.

Abstract

The article deals with the standard immunological model, which is based on the principles of random combination of molecules and cells and their random encounter with their complementary sites, which is accompanied by the formation of reversible complexes and/or a cascade of subsequent reactions. In its purity, such a model gives rise to various kinds of paradoxes that do not correspond to the reality of immune processes. As a rule, the development of immunology is expressed in the construction of more and more detailed links of immunologic events, but the addition of each new event to the chain of links should lead not to acceleration, but to slowing down of the final process within the combinatorial-complementary system. In this connection, the question of a new possible model of the immune system is raised, which is based on P.K. Anokhin’s theory of functional systems. As its further development the physical-information model (PhIM) of the immune system is proposed, which assumes two plans, informational and physical, of the immune system organization and their coordination on the basis of the ideas of organic potential and processes of conjugation. The information plan is represented as an abstract space of degrees of freedom of the system, analogous to phase space in physics. The current and final state of the system can be represented as points of the state space, the activity of the system with the transition from the current to the final state, as a trajectory in this space. The acceptor of the action result in the theory of functional systems of P.K. Anokhin is connected in this case with the image of the final state as the result of the system action. The construction of the trajectory of the system’s activity can be represented as the direction of reduction of the organic potential of the system, by analogy with that in the case of physical systems and their physical potentials. The organic potential reaches a minimum in the final state and expresses the need of the biosystem as a result of action.

Russian Journal of Immunology. 2024;27(4):757-762
pages 757-762 views

Response of lymphoid organs to immunization with Fc fragments of IgG carrying epitopes specific to regulatory rheumatoid factor

Beduleva L.V., Sidorov A.Y., Terentiev A.S., Fomina K.V., Menshikov I.V.

Abstract

Previously, we identified a new factor of autoimmunity downregulation, called regulatory rheumatoid factor (regRF). The production of regRF was associated with the resistance of animals to the experimental autoimmune diseases or with the remission in animals that are sensitive to the autoimmune diseases. The action of regulatory rheumatoid factor is based on the killing of activated CD4 T lymphocytes expressing PD-1, which makes it possible to restrain the expansion of lymphocytes, including autoreactive ones. RegRF-specific epitopes (regRF epitopes) can be induced on IgG Fc fragments. Immunization of rats with homologous IgG Fc fragments bearing regRF epitopes suppresses symptoms, lymphocytic infiltration and target tissue damage in several experimental models of autoimmune diseases. An in vitro study of the mechanisms of regRF-producing lymphocytes activation by IgG Fc fragments carrying regRF epitopes showed that IgG Fc fragments carrying regRF epitopes are T cell-independent antigens type 2. The reactions of the immune system, in particular in lymphoid organs, to T cell-independent antigens type 2, especially having a protein nature, are poorly studied. The purpose of this work is to study the reactions of the spleen and lymph nodes of rats to immunization with IgG Fc fragments carrying regRF epitopes. Wistar rats were immunized subcutaneously with 500 μg of homologous IgG Fc fragments carrying regRF epitopes. Control animals received an injection of phosphate-buffered saline. Immunization with IgG Fc fragments carrying regRF epitopes caused a transient increase of regulatory rheumatoid factor blood level with a maximum on day 7 after immunization. It was found that immunization with IgG Fc fragments carrying regRF epitopes does not cause a reaction in the regional and distal lymph nodes of rats, but induces the development of secondary follicles in spleen that exist for at least 28 days. On day 49, the number of follicles with germinal centers in the spleen of rats immunized with IgG Fc fragments carrying regRF epitopes was lower than in control rats. Consequently, the reaction of splenic follicles in rats immunized with IgG Fc fragments carrying regRF epitopes is transient. No changes were detected in the periarteriolar lymphoid sheaths (splenic T cell zone) in rats immunized with IgG Fc fragments carrying regRF epitopes. Thus, IgG Fc fragments carrying regRF epitopes, being a T cell-independent antigens type 2, do not cause a reaction in the lymph nodes, but induce the development of germinal centers in the spleen that exist for several weeks.

Russian Journal of Immunology. 2024;27(4):763-768
pages 763-768 views

Melatonin as an inducer of Th17 cell differentiation: new mechanisms

Kuklina E.M., Sursyakova N.V., Danchenko I.Y., Glebezdina N.S., Baidina T.V.

Abstract

Cells of the immune system are sensitive to the action of melatonin, and the most obvious target of the hormone is the Th17 T helper subset: in addition to two high-affinity membrane receptors for melatonin, MT1 and MT2, these cells express a nuclear receptor, RORα. Among the secondary messengers involved in the transmission of signals from melatonin receptors, proteins of the sirtuin family are currently of particular interest. It is known that in non-tumor cells, sirtuin 1 (SIRT1) not only increases its expression in response to melatonin, but is also involved in the implementation of melatonin effects, as indicated by inhibitory assays using a specific SIRT1 blocker or corresponding siRNA/shRNA. This relates to the regulation of circadian oscillators, as well as the anti-inflammatory, antioxidant and anti-apoptotic effects of melatonin. Further mechanisms of SIRT1 activity in the cell include transcriptional and posttranscriptional regulation of gene expression through deacetylation of histones and non-histone proteins, and the apparent target of SIRT1 is the transcription factor RORα. It is this factor that mediates classical melatonin/SIRT1-dependent transcriptional control of key circadian regulators, the genes of which have ROR-binding sequences in their promoters. These data raise questions about the functions of SIRT1 in other cells expressing RORα, in particular in Th17 T helper cells, for which it is one of two key differentiation factors, along with RORγt. And if for RORα such a connection still remains hypothetical, for RORγt it has been convincingly demonstrated in studies both in vivo and in vitro: it has been shown that SIRT1 directly binds to RORγt and stimulates the development of Th17 cells, and blockade of sirtuin suppresses the differentiation of these cells in normal and prevents the development of Th17-associated pathology in mice. Summarizing these data, we can confidently predict the existence of a new mechanism for the regulation of the T helper Th17 population by melatonin, through the activation of sirtuin SIRT1, and this mechanism must be taken into account when interpreting data on the immunoregulatory activity of melatonin.

Russian Journal of Immunology. 2024;27(4):769-774
pages 769-774 views

Evaluation of apoptosis markers in patients with atopic dermatitis

Revyakina V.A., Mukhortykh V.A., Tarmaeva N.A., Larkova I.A.

Abstract

The purpose of the study was to analyze indicators of apoptosis in patients with atopic dermatitis (AD). Patients (N = 88) aged from 12 months to 3 years with varying degrees of disease severity were involved into trial. SCORAD indices were: 68.14±2.63 – in patients with severe AD; 32.03±1.43 – with moderate; and 12.12±1.43 – with mild AD, respectively. Determination of apoptosis markers (Caspase 8, Caspase 9, sCD153, sFas-L, Annexin 5) in blood serum was performed using an enzyme-linked immunosorbent assay (ELISA) using commercial kits from Bender MedSystems® (Austria). A study of apoptosis markers in the blood serum of children with AD revealed a significant decrease (p < 0.05) in the concentration of Annexin 5 compared to standard values (by 20 times). A statistically significant decrease (p < 0.05) in the concentration levels of Caspase 8 and Caspase 9 in the serum of AD patients was revealed. Thus, the concentrations of Caspase 8 were reduced on by 3 times, and Caspase 9 by 8 times compared to the norm. Also In addition, when determining sFas-L indicators, a statistically significant (p < 0.05) decrease in concentration was noted compared to standard indicators. The content of sCD153 in the blood serum in AD patients was significantly higher (p < 0.05) than the normative values by 5 times (not detected normally). The most pronounced disturbances in apoptosis indicators were observed in patients with severe atopic dermatitis, (p < 0.05), highlighting the importance of studying apoptosis in the context of AD and the possible link between disruptions in this process and the severity of clinical manifestations in patients. The study demonstrates the peculiarities of apoptosis processes in children with AD. On the one hand, these patients have significantly increased activation of signaling systems, on the other hand, the elimination of altered immunocompetent cells does not occur properly, which contributes to the progression and chronicity of immune inflammation in the skin.

Russian Journal of Immunology. 2024;27(4):775-780
pages 775-780 views

Immuno-RCA for highly sensitive detection of the antigen-antibody complex in the blood group antigen model

Ryazantsev D.Y., Gabrielyan N.G., Polyakova S.M., Zavriev S.K.

Abstract

The problem of detecting tiny quantities of analytes by immunochemical methods has been tried for a long time. One approach is to use nucleic acid amplification methods to amplify the signal from a single antigen-antibody interaction. An amplification method suitable for microarrays is the rolling circle amplification reaction. The principle of the method is usage of a conjugate of a detecting antibody with a primer and subsequent isothermal amplification. The generation of a huge single-stranded reaction product starts after adding the necessary components for amplification reaction: circular oligonucleotides, which serves as a template for amplification and phage phi29 polymerase with the other components. This reaction product consists of a lot of repeats of a nucleotide sequence, that is complementary to the circular template. The fluorescent DNA probe can hybridize to each repeat on the product molecule, resulting in a significantly higher level of fluorescence than with fluorescently labeled antibody or streptavidin development systems. In addition, the reaction product remains immobilized on the surface, allowing usage of this approach for the detection of antigen-antibody interactions in other solid-phase analysis systems, such as microarrays. A common problem with such approaches is the nonspecific sorption of components of the immunochemical reaction or amplification reaction, leading to a high background. It is obvious that no matter how highly sensitive the analysis is in theory, a high background will reduce the entire potential of the method to nothing. Herein, we have developed a method that makes it possible to detect small amounts of antibodies to glycans in blood serum and in swabs from tumor cells in a microarray format using a model of blood group antigens. It was possible to obtain a 30 to 70-fold increase of fluorescence level from a specific interaction compared to the use of fluorescently labeled streptavidin. The method we are developing is promising, as it allows us to significantly increase the signal from the specific antigen/antibody interaction in the glycochip format, which will make it possible to detect antibodies to glycans in samples with a very low concentrations of antibodies, for example, in washes from tumor cells.

Russian Journal of Immunology. 2024;27(4):781-787
pages 781-787 views

Dynamics of clinical and immunological parameters in retinal pigment epithelium transplantation in the context of combined immunosuppressive therapy in the rabbit model of retinal degeneration

Neroeva N.V., Balatskaya N.V., Neroev V.V., Brilliantova A.G., Katargina L.A., Lagarkova M.A.

Abstract

Progressive damage of the retinal pigment epithelium (RPE) underlies the pathogenesis of degenerative retinal diseases such as: age-related macular degeneration (AMD), Stargardt’s disease, retinitis pigmentosa, Best’s disease and others. This group of diseases led by AMD leads to irreversible loss of visual functions, blindness and disability. The possibilities of therapy of late stages of AMD are extremely limited. The most promising approach to replace the damaged retinal pigment epithelium appears to be transplantation of RPE cells derived from induced pluripotent stem cells (iPSC-RPE) into the subretinal space (SRS). Despite immune privilege in the SRS, transplantation of xenogeneic cellular material causes severe inflammation in the posterior segment of the eye and leads to graft rejection in an in vivo experiment in the absence of immunosuppression. The solution to the problem of tissue incompatibility in this case can be the use of combined immunosuppressive therapy (CIT), aimed, on the one hand, at suppression of local inflammation (in the eye) and, on the other hand, at suppression of the systemic transplantation immune response. The aim of the study: clinical and immunological analysis of the results of transplantation of IPSC-RPE suspension on the background of CIT, including single intravitreal intraoperative administration of kenalog and further systemic application of mycophenolate mofetil (MMF), in the model of RPE atrophy in rabbits. Standard and specialized ophthalmological examination was performed at early and distant terms after the intervention in order to clinically assess the posttransplantation process. To analyze the immune status, vitreous humor (VH) and blood serum (BS) of rabbits of the experimental groups were collected. The concentrations of TGF-β1, TGF-β2, and IL-2 were determined in the biomaterial using solid-phase enzyme immunoassay. According to the results of the study, subretinal transplantation of IPSC-RPE, performed against the background of combination of single intravitreal intraoperative administration of kenalog and systemic application of MMF, is a safe method, which provides preservation of the retina and other adjacent structures of the eye and allows to prevent rejection of xenogenic material during its transplantation both in a healthy eye and with pre-formed RPE atrophy, which opens perspectives for full testing of biological effects realized by IPSC-RPE.

Russian Journal of Immunology. 2024;27(4):787-794
pages 787-794 views

The effect of immunosuppressive agent FTY-720 on coagulation, nitroxidergic lung activity and water balance in experimental antiphospholipid syndrome

Urakova M.A., Kapustin I.V., Plekhanova E.S., Pakhmutova P.A., Shaykhullin A.A., Sharaev D.V., Bryndina I. .

Abstract

Antiphospholipid syndrome (APS) is a systemic acquired autoimmune thrombophilia that leads to impaired non-respiratory lung functions due to the circulation of antiphospholipid antibodies, shifting the balance between the coagulation link of hemostasis and the anti-coagulation system towards hypercoagulation. The research examines the modulating effect of FTY-720 on the water balance, coagulation and NO-activity of the lungs under conditions of experimental APS. The functional activity of FTY-720 is largely due to its ability to bind to S1P1 receptors and block signaling pathways mediated by the interaction of the mediator sphingosine-1-phosphate with them. The main effect of FTY-720 is immunosuppression, which develops as a result of the drug’s receptor interaction predominantly with S1P1 receptors, resulting in the retention of autoreactive lymphocytes in lymph nodes, and prevents further spread of inflammation and damage. The experiments were conducted on 85 male rats, divided into groups as follows: The first group of animals (n = 30) was injected with cardiolipin antigen every other day for three weeks for APS modeling; the rats of the second group (n = 25), which served as a control group, were similarly injected with 0.9% NaCl; APS modeling and FTY-720 injection were combined on the remaining animals (n = 30). Three weeks later, arterial (art) and venous (ven) blood was taken, in which APTT and PT were determined using a hemocoagulometer CGL 2110 “Solar” and the corresponding coefficients of APPT of ven/art, PT of ven/ art were calculated. NO-activity was assessed by the content of plasma NO and NO bronchoalveolar lavage obtained by washing the extraction of the bronchopulmonary complex in anesthetized animals. To study the water balance of the lungs, the mass of moist and dried lungs was measured, were determined the total, extra- and intravascular fluid of the lungs. In APS, an increase in APTT and PT of arterial and venous blood was observed, an increase in the level of NO in bronchoalveolar lavages against the background of worsening nitroxidergic activity of the lungs – the NO index of ven/art decreased. There was a positive effect of FTY- 720 on the restoration of non-respiratory lung functions in APS.

Russian Journal of Immunology. 2024;27(4):795-800
pages 795-800 views

Immune system dysfunction in personnel of chemical hazard facilities: purpose and effectiveness of immunotherapeutic drugs

Kozlov V.K., Petlenko S.V.

Abstract

Clinical signs of the presence of immune dysfunction/insufficiency, identified by questioning workers at the landfill for the storage and destruction of industrial toxic waste, were the basis for performing a screening study of immune status. This included a clinical blood test with determination of the leukocyte formula, assessment of the phenotypic status of lymphocytes for the main subpopulations, determination of the concentration in serum immunoglobulins of various classes, assessment of the migration activity of leukocytes, assessment of the microbicidal capacity of neutrophils and their ability to phagocytosis. When the examined employees were found to have more than 20% changes in the normative range of immune status parameters and the presence of combined disorders in different parts of immunoreactivity, in particular combined disorders in the cellular part of the immune system, it was the basis for conducting an in-depth stage of immunoepidemiological examination. This included determination of functional activity cellular elements of the adaptive component of immunity, assessment of the severity of autosensitization, assessment of the severity and specificity of atopic hypersensitization, assessment of cytokine status in normal conditions and in response to mitogen. When assessing the phenotypic status of immunoreactivity cells, it turned out that the absolute number of T lymphocytes (CD3+ phenotype), helper T lymphocytes (CD3+CD4+ phenotype) and killer T lymphocytes (CD3+CD8+ phenotype) was significantly reduced in the peripheral blood of test site employees (p ≤ 0.05, compared with similar indicators in the control group). On the contrary, the content of NK cells (CD3-CD56+ phenotype) tended to increase (both the absolute number and the proportion among other lymphocyte populations). Dysfunction of the cellular component of humoral immunoreactivity (a significant decrease in the absolute number of lymphocytes with the CD3-CD20+ phenotype [B lymphocytes] in the peripheral blood), as well as a significant increase in the concentration of serum IgA-class immunoglobulin and pronounced disimmunoglobulinemia in the serum of the examined individuals (compared to individuals in the control group ) indicated a predominantly inhalation method of exposure to immunotoxic industrial toxicants from the landfill on the immune system. Pathogenetically targeted immune-oriented therapy for the personnel of the test site was carried out with drugs that have thymomimetic activity (cytovir-3, thymogen) and are a means of replacement immunocorrection with a cytokine drug (genetically engineered recombinant yeast IL-2 [roncoleukin]). The established effectiveness of the immunotherapy, in particular the reduction in the incidence rate of various nosological forms of immune-related pathology among the site employees who received immunotherapy and the presence of an immunocorrective effect in the immunoactive drugs used for therapy, indicate the advisability of carrying out preventive medical measures in persons professionally exposed to xenobiotic influences as a component of improving medical provision.

Russian Journal of Immunology. 2024;27(4):801-810
pages 801-810 views

The state of psychological and immunological indicators in graduate students of a medical university

Andreeva I.I., Urazmambetov R.T., Chebotov S.A.

Abstract

Training future doctors for professional practice usually entails building awareness and embracing the significant responsibility inherent in the field. This, in turn, leads to significant psycho-emotional stress by the time of graduation from academic institution. With the aim of identifying the correlation between homeostatic system indicators, a comparative analysis was conducted to characterize the immunological and psychological parameters of final-year medical university students, contingent upon their respective training programs. The study involved sixth-year students of the Therapeutic and Preventive Faculty [TPF] (29 individuals) and the Military Training Center [MTC] (34 individuals) of Rostov State Medical University, a Federal State Budgetary Educational Institution of Higher Education. The exclusion criteria for all participants included the presence of chronic diseases and any infectious process of any origin within three months prior to the study. The groups were similar in terms of age (23.8±1.82 and 23.9±2.2 years, respectively), gender (all male), and corresponded to health group I. Psychological evaluation was conducted employing the Spielberger–Hanin Scale to gauge levels of personal and situational anxiety. The assessment of immunological status was carried out at the Scientific Research Institute of Clinical Immunology using standard methodological approaches. Registration cards for immunopathology analysis were used to characterize health status over the year. Analysis of the obtained data from psychological questionnaires revealed that students of the Therapeutic and Preventive Faculty, compared to their counterparts from the Military Training Center, demonstrated a higher degree of situational and, particularly, personal anxiety. Differences in the immune response system between the compared groups were identified with regards to indicators that characterize both adaptive and innate immunity. These differences were expressed in a more significant number of circulating regulatory T lymphocytes, a less pronounced lytic potential of effector cells, a greater number of TLR9+ monocytes with a decrease in the proportion of cells of the monocyte series carrying HLA-DR in medical students compared to their counterparts studying in the medical service officers’ program. Thus, the period of psychological preparation in a medical university for the commencement of professional activity varies based on the characteristics of the educational process and proves to be more effective for sixth-year students of MTC. Students from the TPF exhibit more pronounced psycho-emotional stress compared to their counterparts in military medical training, leading to evident signs of immune system dysregulation. It is imperative to develop strategies for timely detection of changes in both psychological and immunological adaptive capacities.

Russian Journal of Immunology. 2024;27(4):811-818
pages 811-818 views

Immune alterations in children with autism spectrum disorders

Chudakova Y.M., Nikitina S.G., Balakireva E.E., Shmarin V.V., Salimova T.A., Martynov A.V., Shmarina G.V., Kostyuk S.V.

Abstract

Autism spectrum disorders (ASD) are a heterogeneous group of mental and nervous system disorders. Patients with ASD are characterized by communication and cognitive impairments and obsessive behavior. The pathogenesis and etiology of ASD are still unclear. According to the literature, patients suffering from ASD have not only mental, but also somatic disorders, including changes in the immune system. The aim of this work was to study the concentration of cytokines in the blood plasma of children with ASD and the level of expression of proinflammatory genes in peripheral blood mononuclear cells. The clinical group included 71 children aged 4-12 years with a diagnosis of ASD (F84.02). Patients scored more than 36 on the Childhood Autism Rating Scale (CARS). The control sample included 27 apparently healthy children of the same age. The following methods were used in this study: isolation of mononuclear cells from heparinized peripheral blood, Ficoll-Verografin density gradient centrifugation, evaluation of cytokine blocks using commercially available enzyme immunoassay kits, isolation of random total RNA, reverse transcription using hexaprimers, and real-time polymerase chain reaction using intercalating dye SYBR Green. The concentration of proinflammatory cytokines IL-1β, IL-8, and IL-17A in the peripheral blood plasma of children with ASD was statistically significantly increased compared to the control sample. Moreover, the concentration of the anti-inflammatory cytokine IL-10 in patients with ASD was 3.6 times lower compared to the control sample (p < 0.001). The level of expression of the NF-κB1, IL1β, IL8 and TNFα genes at the RNA level in peripheral blood mononuclear cells was increased by 2.8, 2.5, 4.8 and 4.2 times in patients with ASD compared to the control sample (all p < 0.01). The results obtained indicate an increase in the concentration of proinflammatory cytokines (IL-1β, IL-8, IL-17A) in the blood plasma and a decrease in the concentration of anti-inflammatory cytokines (IL-10) in patients with ASD compared to the control sequence.

Russian Journal of Immunology. 2024;27(4):819-824
pages 819-824 views

Expression of key molecules of the classical inflammation activation pathway in blood leukocytes of autistic children

Alekseeva A.S., Filippova Y.Y., Burmistrova A.L.

Abstract

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders, whose causes are currently not fully understood. Research suggests that inflammation and changes in immune functions may play an important role in the development of autism. Increased levels of proinflammatory cytokines in the brains of autistic children lead to negative regulation of synaptic plasticity, as well as impaired proliferation and differentiation of neurons through activation of the nuclear factor kappa B (NF-κB) signaling pathway. The purpose of the work is to analyze the levels of mRNA: TLR2, TLR4, MyD88, IκBα, NF-κB p50, NF-κB p65 in peripheral blood leukocytes of children in comparison with the severity of autism spectrum disorders. The study included 126 children aged from 3 to 13 years (the ratio of boys to girls was 4:1): 45 children with typical neurodevelopment, and 81 children with a clinically confirmed diagnosis of autism. According to the Childhood Autism Rating Scale, 51 children had mild to moderate ASD (CARS score: 29-36), and 30 children had severe autism (CARS score: 36-60). The expression of inflammatory signal transduction pathway molecules was determined in peripheral blood leukocytes using real-time polymerase chain reaction with SYBRGreen. To compare the samples, one-way ANOVA and Tukey’s test were used. It was found that in leukocytes of children with severe ASD, the expression of the adapter protein MyD88 and the p65 subunit of the nuclear transcription factor NF-κB was significantly reduced, and the expression of the NF-κB inhibitor, IκBα, was significantly increased, compared to the control group. In leukocytes of children with mild ASD, a decrease in NF-κB p65 expression was found at a trend level. When comparing groups of children with different severity of autism symptoms (mild/severe), no significant differences were found in the levels of mRNA of key signaling molecules of the classical inflammation activation pathway in blood leukocytes. Thus, in the blood leukocytes of children with severe ASD, suppression of the expression of key molecules of the classical inflammation activation pathway (NF-κB) is observed, which leads to a decrease in the expression of pro-inflammatory cytokines: IL-1β, IL-18 and IL-2, against the background of increased expression of key cytokine of Th1 cells – IFNγ.

Russian Journal of Immunology. 2024;27(4):825-830
pages 825-830 views

The influence of modulation of intestinal microbiota on clinical and immunological parameters and oxytocin levels in children with autism spectrum disorders

Cherevko N.A., Novikov P.S., Khudyakova M.I., Arkhipov A.M., Loginova E.A., Vekovtsev A.A., Bylin P.G.

Abstract

Autism spectrum disorders are associated with an imbalance of immune and neurological disorders, starting after the age of two. The study is devoted to studying the role of specialized strains of bacteria Lactobacillus reuteri, which mediate the synthesis of oxytocin in humans and influence inflammation indicators. Bacteria of this strain were part of the biologically active additive “Panbiolact Mental”, developed and presented by NPO ArtLife (Tomsk). The purpose of the work was to assess the effect of specialized strains of bacteria Lactobacillus reuteri on changes in the composition of the intestinal microbiota, oxytocin levels, and immune parameters of children with ASD. The study included 43 children with autism spectrum disorders who took Panbiolact Mental for 90 days. The study materials included venous blood samples and fecal samples. The concentrations of cytokines (IL-4, IL-10, TNF, IFN), immunoglobulins (IgE, IgG, IgA, IgM) and the neuropeptide oxytocin were determined in the blood serum. Fecal samples were used to assess the qualitative and quantitative composition of the colon microbiota. Clinical symptoms of the disease associated with quality of life were assessed using the standard ATEC test scale (Autism Treatment Evaluation Checklist), expressed in scores corresponding to the severity of clinical and neurological parameters of the disease. In children with autism spectrum disorders, after 90 days of regular use of Panbiolact Mental, the number of bacteria of the genera Acinetobacter decreased, the number of Bacteroides species pluralis, Akkermansia muciniphila, Eubacterium rectale, Prevotella species pluralis and Methanobrevibacter smithii increased. Increases in the concentration of oxytocin, the protolerogenic coefficient IL-10/TNFα, immunoglobulins M and G, and a decrease in the concentrations of TNFα and IL-10 were recorded. The results of the study support the hypothesis of a significant role of gut microbiota diversity in the neuro-immune pathogenesis of autism spectrum disorders. “Panbiolact Mental” is presented as a potentially effective remedy for an integrated approach to the correction of ASD in children. These data may form the basis for further research in the field of probiotic therapy, as well as for the development of new strategies based on modulation of the intestinal microbiota.

Russian Journal of Immunology. 2024;27(4):831-838
pages 831-838 views

Specific features of cytokine synthesis in adolescent girls with oligomenorrhea and low body mass index

Kamalov T.M., Muzafarova S.A.

Abstract

The article is devoted to the study of the cytokine component of immunity in teenage girls with oligomenorrhea, underweight and with normal body weight in comparison with teenage girls with a normal menstrual cycle and normal body weight, which is of great importance to pediatric gynecology. Studying of the cytokine profile in oligomenorrhea will allow early identification of the development of many gynecological pathologies, including polycystic ovary syndrome, endometrioid neoplasms, as well as for understanding the pathogenesis of these conditions and developing approaches to their diagnosis and treatment, which is of great practical importance. The authors conducted an immunological study of teenage girls with oligomenorrhea with underweight and normal body weight in comparison with teenage girls with a normal menstrual cycle and normal body weight. Purpose of the study: to study the levels of IL-6, IL-17A, IL-18 and IL-10 in adolescent girls with oligomenorrhea and underweight. Teenage girls (N = 52) aged 13 to 17 years with established menstrual irregularities were examined. The control group consisted of 24 practically healthy girls of the same age. From the study, it was established that girls with oligomenorrhea and underweight have a pronounced increased synthesis of proinflammatory cytokines IL-6, IL-17A and IL-18. In the same group of girls, an increase in the level of the anti-inflammatory cytokine IL-10 was detected, which may be an attempt by the body to compensate for inflammatory processes. However, IL-10 levels remain elevated, which may indicate an immune imbalance. The discovered imbalance in the cytokine profile emphasizes the complexity of the pathogenesis of oligomenorrhea in girls with underweight, and the identified levels of the studied cytokines can serve as biomarkers that will help in diagnosis, assessment of severity, and prediction of the course of the disease state.

Russian Journal of Immunology. 2024;27(4):839-844
pages 839-844 views

Growth factor dysregulation and placental dysfunction

Azizova Z.S., Eshimbetova G.Z., Zhuraeva D.M.

Abstract

The article is devoted to the study of angiogenic and antiangiogenic vascular growth factors in placental dysfunction, which is of great importance in obstetrics and perinatology. The study of growth factors as predictors of the development of placental dysfunction makes it possible to determine in advance the development of many obstetric pathologies, including preeclampsia and fetal growth retardation, which is of great practical importance. The authors conducted an immunological study of pregnant women with placental dysfunction and pregnant women with a physiological pregnancy. Purpose of the study: to study serum growth factors in women with placental dysfunction.

We examined 47 pregnant women with a gestation period of 26-40 weeks, with a diagnosis of placental dysfunction, who were under observation in the obstetric department of the city maternity complex No. 3 of the city of Tashkent. The control group consisted of 35 women with a physiological pregnancy. All women underwent an immunological blood test: cellular and humoral immunity, as well as cytokines (VEGF-A, PlGF, sFlt-1, sFlt-1/PlGF) were studied. Based on the results obtained, the authors suggest that an increased level of soluble sFlt-1 and a simultaneous decrease in the levels of VEGF-A and PlGF in pregnant women at 26-40 weeks of gestation may portend the development of pregnancy complications, including preeclampsia and fetal growth restriction, and increase the risk of premature birth. Ddelivery due to impaired placental blood flow and oxygen deficiency for the fetus, lead to deterioration of microcirculation, and insufficient levels of VEGF-A and PlGF can contribute to vascular endothelial dysfunction, which can also contribute to the development of preeclampsia. The studied angiogenic and antiangiogenic vascular growth factors are important indicators and can serve as markers for predicting pregnancy complications for active medical intervention in maintaining the health of both mother and child.

Russian Journal of Immunology. 2024;27(4):845-852
pages 845-852 views

Synthesis of cytokines during physiological pregnancy

Khamdamov B.Z., Turdyeva D.O., Rustamova N.B.

Abstract

The article is devoted to the study of the level of pro- and anti-inflammatory cytokines in women with a physiological pregnancy, which is of great importance in obstetrics. Studying the synthesis of cytokines makes it possible to identify disturbances in the course of pregnancy, which is of great practical importance. The authors conducted a study of the level of cytokines in women with physiological pregnancy. Purpose of the study: to study the serum concentration of pro-inflammatory (IL-1β, IL-6, TNFα, IFNγ) and anti-inflammatory (IL-4, IL-10) cytokines in the dynamics of physiological pregnancy.

The level of serum cytokines was studied in 94 women with a physiologically progressing pregnancy, who were registered with advisory clinics No. 14, No. 26, and No. 28 in Bukhara. The age of pregnant women ranged from 21 to 37 years, averaging 26.3±1.5 years. When compiling groups by trimester of pregnancy, it was revealed that: 35 women were in the first trimester of pregnancy; in 31 – the second trimester; and in 28 women – the third trimester of pregnancy. The control group consisted of 30 practically healthy non-pregnant women who were comparable in age. The levels of cytokines 1β, IL-6, TNFα, IFNγ, IL-4, and IL-10 was determined in peripheral blood serum using a set of reagents produced by Cytokin LLC (St. Petersburg, Russia) using the ELISA method according to the manufacturer’s instructions. Statistical processing of the obtained results was carried out using Student’s t-test using the standard Windows 2000 statistical software package. An increase in the level of proinflammatory cytokines (IFNγ, TNFα) was detected in the early stages of gestation compared with data from healthy non-pregnant women, which persisted in the second half of pregnancy against the background of an increase in anti-inflammatory cytokines (IL-4, IL-10). In the third trimester of pregnancy, a further increase in the serum level of pro-inflammatory cytokines (IL-1β, TNFα, IFNγ) was observed. The results of the studies indicate that at the level of the cytokine network there are mechanisms of fetoprotection, the violation of which can be the cause of pregnancy pathology.

Russian Journal of Immunology. 2024;27(4):853-858
pages 853-858 views

Cytokine balance in pregnant women with preeclampsia

Musakhodzhaeva D.A., Rustamova N.B., Sadykova H.Z.

Abstract

Studies were conducted to study the levels of pro- (IL-6, IL-18, IL-17A) and anti-inflammatory (IL-4) cytokines in the blood serum of pregnant women at different stages of gestation: 18-20, 28-30, and 33- 38 weeks. The study involved 76 patients at risk of developing preeclampsia. Of these, 34 women developed preeclampsia, making up the main group, and 42 pregnant women had no symptoms of preeclampsia and made up the comparison group. The control group consisted of 28 somatically healthy women with a physiologically normal pregnancy. The average age of the examined patients with preeclampsia was 26.2±4.3 years, and in the group of pregnant women with normal pregnancy it was 25.8±4.7 years. The purpose of the study was to study the levels of cytokines IL-4, IL-6, IL-17A, and IL-18 in women with uncomplicated pregnancy and preeclampsia. These cytokines play an important role in the immune response and may be associated with the development of preeclampsia. The results of the study may help further understand the mechanisms of the disease and develop strategies for its prevention and management.

The levels of pro- (IL-6, IL-18, IL-17A) and anti-inflammatory cytokines (IL-4, IL-10) were studied in blood serum by ELISA using test systems of Vector-best JSC (Novosibirsk, Russia) in accordance with the manufacturer’s recommendations. Statistical processing of research results was carried out using variation statistics methods. The results are presented as the sample mean (M) and standard error (m). The significance of the differences in the mean values (P) of the compared indicators was assessed using the Student t test (t). A study conducted by the authors found the following patterns in interleukin (IL) levels in pregnant women at risk of developing preeclampsia (PE). The levels of IL-6, IL-17A, and IL-18 were significantly increased in pregnant women with PE. There was a tendency to decrease the levels of IL-4, and IL-10 in women at risk of developing preeclampsia. These findings may help guide further research and development of strategies to prevent and manage preeclampsia in pregnant women.

Russian Journal of Immunology. 2024;27(4):859-864
pages 859-864 views

Hyperemesis gravidarum is a cytokine storm?

Djabbarova Y.K., Abdieva S., Suyarkulova M.E.

Abstract

Aim. To study the systemic response of proinflammatory cytokines in women suffering from VP. The main group consisted of 47 women with VP, which was divided into 3 subgroups according to severity: the 1st – included 16 patients with mild VP, the 2nd – 15 with moderate severity, and the 3rd – 16 women with severe VP. The control group consisted of 10 pregnant women with a physiological course without signs of toxicosis. Interleukins (IL-1β, IL-6, TNFα) were determined in the blood serum of pregnant women by solid-phase ELISA using Cytokine test kits (St. Petersburg, Russia).

With increasing severity of toxicosis, there is a significant increase in IL-1β in severe VP – 1.9 times higher than the same value of the norm (p < 0.05), 2 times higher than in mild vomiting (p < 0.05), and in 1.7 times – with moderate VP (p < 0.05). The study of the level of IL-6 revealed a directly proportional increase in the indicator with increasing severity of toxicosis in relation to the control indicator: with mild vomiting – 1.9 times (p < 0.05), with moderate vomiting – 2.6 times (p < 0.001), and in severe VP – 2.9 times (p < 0.0001). A significant decrease in the level of TNFα was observed with increasing severity of toxicosis in relation to the control indicator: with mild vomiting – by 1.5 times (p < 0.05), with moderate vomiting – by 1.9 times (p < 0.05), and with severe VP – 2.1 times (p < 0.05).

Excessive secretion of proinflammatory cytokines IL-1β and IL-6 (2 and 3 times, respectively), exceeding the norm, with a sharp suppression of TNFα production (2 times) can be considered as predictors of a “cytokine storm”, clinically occurring with multiple organ failure up to death if the pregnancy is not terminated in a timely manner.

Russian Journal of Immunology. 2024;27(4):865-870
pages 865-870 views

Disorders in cytokine synthesis in women with uterine fibroids

Isanbaeva L.M., Musakhodzhaeva D.A., Narzulloeva N.S.

Abstract

In the structure of gynecological diseases, uterine fibroids occupy an “honorable” second place after inflammatory processes of the genital organs, and its share reaches 40%. Uterine fibroids are a benign monoclonal tumor that develops from one abnormal smooth muscle cell of the myometrium, which, as a result of mutation, has the ability to grow unregulated. Common symptoms of the disease include pelvic discomfort or pain, excessive uterine bleeding, secondary anemia, infertility, and bowel and bladder dysfunction. Uterine fibroids can negatively affect the general condition of a woman, causing hormonal, vegetative-vascular and psycho-emotional disorders. Moreover, about 80% of patients with uterine fibroids undergo radical surgical treatment. The mechanisms of development and growth of this benign tumor have not been fully established and remain controversial. The role of immune disorders in the pathogenesis of fibroids is currently being discussed. It has been proven that the growth of fibroids is accompanied by a weakening of immune defense against the background of an increase in the level of proinflammatory cytokines, which are regulators of the processes of proliferation and apoptosis, mediators of the action of sex steroids. The aim of the study was to study the level of some pro-inflammatory cytokines (IL-1β, IL-2, TGF-β2 and MCP-1) in the blood serum of women of reproductive age with uterine fibroids, depending on the size and nature of tumor growth. A comparative analysis of the results of examination of 123 women with uterine fibroids, who made up 2 groups: 1st group of 65 women with simple uterine fibroids and 2nd group of 58 women with rapidly growing uterine fibroids, is presented. The examination included a comprehensive clinical and laboratory study. The level of cytokines (IL-1β, IL- 2, TGF-β2, MCP-1) in the blood serum was assessed by ELISA. It was found that in patients of reproductive age with uterine fibroids, there is an increase in the levels of IL-1β, TGF-β2 and MCP-1. In women with rapidly growing uterine fibroids, these changes are more pronounced. The concentration of IL-2 is reduced in all women with uterine fibroids, regardless of the size and nature of tumor growth. It has been established that an increase in the size of myomatous nodes is accompanied by an increase in immune imbalance: there is an increase in the levels of pro-inflammatory cytokines (IL-1β, TGF-β2, MCP-1) against the background of a reduced content of the lymphokine IL-2, which we regard as possible links in the pathogenesis of uterine fibroids. A pronounced deficiency of IL-2 in the blood serum against the background of a sharp increase in the concentration of TGF-β2 and MCP-1 in the blood of women with uterine fibroids can be considered as a negative criterion for predicting disease progression and used as an additional prognostic marker of tumor growth

Russian Journal of Immunology. 2024;27(4):871-876
pages 871-876 views

Characteristics of the proinflammatory response of monocytes/macrophages in patients with metabolic syndrome, exemplified by the production of IL-6 and MCP-1

Malashchenko V.V., Khaziakhmatova O.G., Yurova K.A., Todosenko N.M., Bograya M.M., Gazatova N.D., Melashchenko O.B., Beletskaya M.A., Litvinova L.S.

Abstract

Metabolic syndrome (MS) is one of the most common socially significant diseases. Around 1.9 billion people suffer from this disease, which places an enormous burden on healthcare systems around the world. This is particularly true in connection with concomitant diseases. With the progression of MS, disorders in the function of the immune system occur in the body, including those associated with mitochondrial dysfunction, leading to the development of chronic inflammation. In particular, there is an increase in the number of circulating monocytes actively recruited to inflamed adipose tissue, where there is non-specific proinflammatory activation of innate immune cells, which adopt an M1-like phenotype and become less sensitive to anti-inflammatory stimuli. This ultimately leads to a decrease in the functional activity of monocytes/macrophages and their immunoplasticity. The subject of the study was the venous blood of patients and the CD14+ monocytes/macrophages obtained from it by immunomagnetic separation. In our work, we focused on the search for significant relationships between markers of chronic inflammation and the formation of immune tolerance of monocytes/macrophages in patients with metabolic syndrome. Biochemical parameters, basal and LPS-stimulated production of proinflammatory cytokines (IL-6 and MCP-1) were investigated by culture of monocytes/macrophages in patients with metabolic syndrome. The evaluation of biochemical parameters in blood samples from MS patients and healthy donors revealed that the levels of ALAT, AST, GGT, alkaline phosphatase, uric acid, C-reactive protein, glucose and insulin were significantly higher in MS patients than in healthy donors. The levels of P-amylase and high-density lipoprotein were significantly lower than in the control group.

Within the experimental model, repeated stimulation showed a decrease in cytokine production in response to LPS compared to the first stimulation on day 7. It was also found that the response to the primary stimulus was higher in cells from patients with a body mass index (BMI) > 40 kg/m2, which could indirectly indicate the presence of a phenotype associated with chronic inflammation and consequently with reduced plasticity of the monocyte/macrophage immune response.

Russian Journal of Immunology. 2024;27(4):877-882
pages 877-882 views

Antibodies to HIV-1 gp120 in an experimental model of atherosclerosis caused by immunization with native high-density lipoproteins

Snigirev A.Y., Terentieva O.S., Shklyaeva N.P.

Abstract

Antibodies to bacterial and viral antigens are detected in some systematic autoimmune diseases in the absence of infection. Autoimmune MRL mice and patients with mixed connective tissue disease produce antibodies to gp120 HIV-1, despite the fact that they had never been exposed to HIV-1. Conversely, viral infections may be accompanied by pathological autoimmune reactions. Reactivity to viral antigens in autoimmune diseases and autoimmune reactions in viral diseases are caused by the induction of antibodies via idiotype-anti-idiotype interactions between autoclones and lymphocyte clones against foreign antigens or homology of foreign antigens and autoantigens. Cardiovascular diseases caused by atherosclerosis are currently one of the main causes of mortality in HIV infected patients. It is assumed that HIV infection accelerates atherogenesis. The mechanisms of the association between HIV infection and atherosclerosis are not completely clear. Chronic activation of the immune system, disturbance of cytokine regulation caused by HIV infection, induction of autoantibodies against oxidized low-density lipoproteins (LDL) and antibodies to ApoB-D are considered as possible factors of atherogenesis in HIV infection. The aim of this research was to determine whether an atherogenic immune response against native human high-density lipoproteins (nHDL) could induce antibodies to gp120 HIV-1. Studies were conducted on model of autoimmune atherosclerosis caused by immunization with native human HDL in rabbits. Rabbits (n = 6) were one-time intradermally immunized with human nHDL at a dose of 200 μg of protein per animal in incomplete Freund’s adjuvant. Antibodies to gp120 HIV-1 were measured before immunization of rabbits and on the 28th and 42th day after immunization with HDL, and antibodies to HDL were weekly measured within 42 days after immunization. Histological analysis of the aorta was conducted after eight months after immunization. Transient anti-gp120 HIV-1 antibody production was detected in rabbits immunized with native HDL. The appearance of antibodies to gp120 HIV-1 in response to immunization with native HDL which causes atherosclerosis suggests that the immune response to gp120 HIV-1 during HIV infection may be accompanied by the production of atherogenic antibodies to HDL. Consequently, the antibodies to native lipoproteins caused by an immune response against gp120 HIV-1 may be a factor in atherogenesis during HIV-1 infection.

Russian Journal of Immunology. 2024;27(4):883-886
pages 883-886 views

Phagocytic activity and proinflammatory activation potential of smooth muscle cells of the Tunica intima of human aorta under experimental conditions

Khovantseva U.S., Matveeva D.K., Chakal D.A., Breshenkov D.G., Charchyan E.R.

Abstract

The aorta is the largest blood vessel in the body, which reaches a diameter of about 3 cm and is responsible for transporting oxygen-enriched arterial blood from the heart to tissues and organs. The aortic wall consists of three layers: the inner Tunica intima, the middle Tunica media and the outer Tunica adventitia. The layers of the aortic wall have a diverse cellular composition and include smooth muscle cells (SMCs), fibroblasts, endothelial cells, etc. Functional disorders in the cells of the intima of the human aorta can lead to various cardiovascular diseases (СVD), such as aneurysm and, as a result, dissection or rupture of the thoracic aorta. The cellular and molecular mechanisms of CVD development remain not fully understood, therefore, the study of the functional characteristics of various cell populations that make up the human aorta is an urgent task today. The aim is to evaluate the inflammatory response formed by cells that are part of the Tunica intima of the human aorta during phagocytosis of latex particles and internalization of low-density lipoproteins (LDL) to study their role in the development of aneurysms. The experiments were performed on smooth muscle cells (SMCs) isolated from the intima of the human aorta in patients with aneurysm. Phagocytic activity was studied by adding latex beads to the SMCs of Tunica intima, the ability to internalize LDL was evaluated using the BDP 630/650 dye and a biochemical method, the assessment of the ability to pro- and anti-inflammatory activation was studied using enzyme-linked immunosorbent assay (ELISA). Our results demonstrated that the absorption of latex beads and LDL stimulates the activation of interleukin secretion by smooth muscle cells that are part of the Tunica intima of the aorta, namely the proinflammatory cytokines IL-6 and IL-8. This fact may indicate that in the conditions of the body, the human aortic intima SMCs phenotype may switch from contractile to secretory or macrophage-like, which indicates the participation of this phenotypic cell transition in the process of aneurysm development.

Russian Journal of Immunology. 2024;27(4):887-892
pages 887-892 views

Patients with coronary atherosclerosis had an altered ratio of monocyte subpopulations in the blood, which was associated with an inflammatory cell response

Verkhova S.S., Nikiforov N.G., Chegodaev E.S., Popov M.A.

Abstract

Coronary artery disease (CAD) is one of the leading causes of death in developed countries. Experimental data confirm the role of monocytes in the development of CAD. Three main subpopulations of circulating blood monocytes are known: classical CD14++CD16- (~80%), intermediate CD14+CD16+ (~5%) and non-classical CD14+CD16++(~15%). It is believed that each of the subpopulations of monocytes performs different functions. There are studies that demonstrate that classical monocytes respond more to the bacterial presence, whereas non-classical ones respond to the viral one. However, the functions of monocyte subpopulations have not been fully studied. Previously, we demonstrated that circulating monocytes of the blood of patients with atherosclerosis had increased proinflammatory activity. We decided to find out how the ratio of monocyte subpopulations in the blood is related to the inflammatory response of cells in atherosclerosis. The aim of our work was to investigate the relationship of the inflammatory response of primary monocytes with the distribution of monocyte subpopulations relative to the total pool of monocytes in healthy and sick CAD. The study included 20 men aged 46 to 70 years, 10 of them without CAD and 10 patients with CAD. A coronary angiography was performed, according to the results of which the patients were divided into patients with coronary atherosclerosis with detected stenosis in 2 or more arteries (CAD) and healthy ones without stenosis in the arteries. Next, blood was taken to study circulating monocytes. Monocyte subpopulations were detected by flow cytometry from the leukocyte fraction using antibodies against CD14- FITC and CD16-PB450-A. Immediately after isolation, monocytes were stimulated with LPS with a final concentration of 1 ug/mL, and a supernatant was selected 24 hours later for further enzyme immunoassay. The inflammatory response was assessed by the secretion of cytokines TNFα, IL-1β, IL-6, IL-8, IL-10, and CCL2 using ELISA. The monocytes of CAD patients had an altered inflammatory response in response to LPS stimulation compared to patients without CAD. This was manifested in increased secretion of IL-1β and TNF, and decreased secretion of CCL2 and IL-6. An increase in the number of intermediate and non-classical monocytes in patients with CAD was associated with changes in the inflammatory response of cells to the secretion of cytokines IL-1β and CCL2. It can be assumed that pathological changes in the representation of monocyte subpopulations in the bloodstream may be one of the causes of chronic inflammation in the walls of the arteries, contributing to the progression of atherosclerotic lesions.

Russian Journal of Immunology. 2024;27(4):893-898
pages 893-898 views

Determination of proinflammatory cytokine levels to assess the reparative potential of tissues in ischemic damage and local correction with hyaluronic acid

Shperling M.I., Kubyshkin A.V., Uryupin K.I.

Abstract

The hypothesis of the study was the assumption that local correction of secondary alteration stops excessive inflammation activity and promotes early activation of reparative processes. Objective: in an animal experiment, to evaluate the dynamics in blood plasma of the concentration of circulating inflammatory cytokines in acute ischemic damage to soft tissues and after local action of a hyaluronic acid-based drug.

In anesthetized Wistar rats, acute ischemic damage to the soft tissues of the thigh was simulated by mechanical compression with a vise for 7 hours. After removing the vise, the rats were divided into 2 groups of 32 individuals: control (without treatment) and experimental (3 hours after removing the vise, the drug was injected into the area bordering the compression zone with a sterile syringe based on hyaluronic acid “Hyalift-3.5”, diluted with 0.9% solution to the final concentration of the drug – 1.75%). The concentration of cytokines in blood plasma was determined, histological sections of soft tissues in the compression area were examined.

An increase in the plasma concentration of proinflammatory cytokines (IL-1β, TNFα, IL-6) was revealed during the entire follow-up period (21 days), especially 7 days after the injury. To the greatest extent, these changes were observed in animals in the control group, which was manifested by a statistically significant increase in the concentration of IL-1β, TNFα and IL-6, relative to the values in intact rats: on average by 7.2; 3.7 and 5.3 times, respectively. In rats in the experimental group, local administration of a hyaluronic acid-based drug already in the early period after injury limited the severity of inflammation (an increased concentration of IL-10 was recorded in blood plasma).

The sanogenetic role of local administration of hyaluronic acid in the wound process is mediated by the relief of inflammation in the early period of damage and is realized in increasing the reparative potential of tissues according to the variant of earlier and significant formation of musculoskeletal tissue regenerates.

Russian Journal of Immunology. 2024;27(4):899-906
pages 899-906 views

Modern problems of sensitization to panallergens

Zheltikova T.M., Akhapkina I.G., Antropova A.B., Konishcheva A.Y., Mazurina S.A., Mokronosova M.A.

Abstract

Pan-allergens are molecules, mainly proteins of various families, responsible for cross–reactivity to a wide range of related and unrelated allergens. The clinical significance of having sensitization to some pan-allergens, for example, nsLTP, parvalbumins, storage proteins grows from the fact that severe, generalized reactions can develop, for example, nsLTP syndrome. Sensitization to pan-allergens depends on many factors, such as geographical location, age, food preferences, socioeconomic characteristics of the patient. The aim of the study is to identify the pattern of the sensitization to various molecules of pan-allergens in patients with allergic diseases living in the central part of Russia.

We analyzed the sera of a total of 556 patients with allergic diseases in a multiplex enzyme immunoassay. Six profilin molecules, 2 polcalcin molecules, 12 – nsLTP, and 7 parvalbumin molecules were used.

The frequency of IgE-ab to profilins in patients in central Russia is low (5-7%). At the same time, almost all patients with IgE-ab to profilins have IgE-ab to Bet v 1 (PR-10) and concomitantly to other profilins. In this regard, Bet v 1 can be considered as a primary sensitizer. The peculiarity of sensitization to polcalcins and LTPs was the low frequency of detection of IgE-ab to them (from 0.2% to 3%). At the same time, neither the nsLTP molecules of a peach, nor even apples, which are often consumed in central Russia, provoke the development of nsLTP syndrome. The detection rate of IgE-ab to parvalbumin in the sera of all patients with allergic reactions is also relatively not high and is 7-10%. Whereas the frequency of detection of IgE-ab to parvalbumins in the sera of patients with fish allergy is very high and reaches 63-90%. As a rule, IgE-ab are detected to all molecules, i.e., for parvalbumins of all studied fish species.

The sensitization profile to profilins, polcalcins, nsLTP and parvalbumins in patients living in central Russia has its own unique characteristics. One of the primary sensitizers in patients with sensitization to pollen of wind-pollinated trees is Bet v 1 (PR-10 homologue), IgE-ab to which was detected in 42% of patients. The detection rate of IgE-ab for various molecules of pan-allergens in general was low as follows: profilins – 5-7%, polcalcins – 0.5%, nsLTP – 0.2-3%, and parvalbumins – 7-10%.

Russian Journal of Immunology. 2024;27(4):907-912
pages 907-912 views

Rank correlation between atopic comorbidity and laboratory parameters in allergic rhinitis

Kukharev Y.V., Klimov A.V., Klimov V.V., Tcherbik N.V., Shkatova A.N., Slezkin M.I., Huseinova K.D.

Abstract

One of the current cutting-edge problems in allergy and ENT is the study of comorbidity in allergic rhinitis, which is the most common atopic disease among all other atopies. Two decades ago, a new endotype of the disease, local allergic rhinitis, was discovered. In the past, some patients with typical complaints of chronic nasal congestion, persistent runny nose, and other similar symptoms, did not display such characteristic diagnostic criteria as positive allergy skin tests and an increased value of serum total IgE and specific IgE antibodies. They were qualified by allergists and ENT specialists as individualists with non-allergic rhinitis and, accordingly, did not receive adequate treatment. However, their symptoms remained, prompting them to abuse decongestants and resulting in an increased burden on the cardiovascular system. This, along with the burden of concomitant pathology, including other atopies, can be considered a significant medical and social problem. With the purpose to study rank correlation between comorbidity and three laboratory biomarkers, 46 patients with allergic rhinitis were examined. The list of parameters included two routine items such as serum total IgE and eosinophilic cationic protein, and rarely studied IL-4 in skin exudate. Clinical analysis showed that significantly more often allergic rhinitis in patients was combined with bronchial asthma (in 39.1%, p < 0.05), less often with food allergy (in 19.6%), atopic dermatitis (in 10.9%), insect allergy (in 8.7%), and allergic urticaria (in 4.5%). In one case, local perennial rhinitis was identified, accompanied by conventional seasonal rhinitis with a high content of serum total IgE and positive allergic skin tests with pollen allergens. Skin tests with household allergens, including house dust mite products, showed a negative result. This case was regarded as a manifestation of the so-called “double” allergic rhinitis. The Spearman correlation demonstrated a negative mean strength relationship between comorbidity and serum IgE and eosinophilic cationic protein (p < 0.05). The seemingly paradoxical result can be interpreted quite logically, taking into account immunopathogenetic mechanisms of allergic inflammation. In particular, with an increase in the frequency of atopic comorbidity, the migration of eosinophils from the blood to sites of eosinophilic inflammation increases.

Russian Journal of Immunology. 2024;27(4):913-918
pages 913-918 views

The role of immuno-mediated dysregulation in the progression of allergic pathology in military personnel under occupational stress

Zaitseva N.S., Sizyakina L.P., Urazmambetov R.T.

Abstract

In order to identify clinical and immunological predictors of the progression of allergopathology in military personnel participating in special operations under conditions of professional stress, 43 military personnel participating in special operations divided into two groups were examined. Group 1 consisted of officers with allergopathology or who first debuted symptoms of allergic diseases during or within 6 months after participating in special operations (n = 13, average age 36.4±4.5 years). Group 2 included officers participating in special operations who did not have symptoms of allergic diseases (n = 13, average age 36.4±4.5 years). The analysis of complaints and medical documentation were carried out. Clinical and laboratory examination was performed without exacerbation of somatic pathology. The immune status was assessed by the expression of CD3+, CD4+, CD8+, CD16+, CD19+, HLA-DR+, intracellular FoxP3 content in CD4+CD25+T cells, granzyme B in CD3-CD16+ and CD3+CD8+ lymphocytes using appropriate monoclonal antibodies (Beckman Coulter) and taking into account the results on the cytofluorometer “FC 500”. Immunological monitoring was performed before participation in hostilities and 6 months after return. A comparative assessment of the cellular and humoral state of military personnel of both comparison groups before leaving for an area with an unfavorable operational situation revealed the following differences. In the group of military personnel with allergic manifestations, significantly fewer CD4+ lymphocytes were noted, as well as significantly fewer CD3+CD4+CD25+FoxP3 regulatory lymphocytes and an increase in the number of circulating B lymphocytes were recorded. When dynamically monitoring the parameters of the cellular and humoral immune response in military personnel participating in hostilities, 6 months after returning from a business trip to areas with an unfavorable operational situation, unidirectional changes in the immune status were recorded in the form of a violation of the differentiation processes of the T cell link of the immune system. In the group of servicemen suffering from allergic diseases, the revealed changes were accompanied by a weakening of the processes of physiological immunosuppression in the form of a persistent decrease in the content of regulatory T lymphocytes in the dynamics of observation for 6 months.

Russian Journal of Immunology. 2024;27(4):919-924
pages 919-924 views

Allergic rhinitis: a brief overview of the etiopathogenesis and rehabilitation of patients

Ignatova I.A., Ivanenko D.B.

Abstract

The article presents a brief overview of modern literature sources concerning the prevalence, etiopathogenetic approaches in the diagnosis and treatment of allergic rhinitis. The relevance of the problem under consideration is due to the high prevalence of this pathology, the variety of etiopathogenetic mechanisms and the variability of classifications. One of the most popular classifications is seasonal. When studying pathogenetic mechanisms, the following patterns were revealed: the nasal mucosa is the main air conditioner of the respiratory tract and the first line of defense against infectious agents transmitted by airborne droplets. These roles require maintaining and restoring epithelial integrity and the ability to initiate immune responses. When conditions or factors are present that compromise the integrity of the mucosa, the epithelium releases alarmins and other molecular patterns associated with damage that trigger repair mechanisms but can also cause protective inflammation. In allergic rhinitis, the same mechanisms can activate the development of the disease. Many authors consider various diagnostic methods for allergic rhinitis. Such as a detailed and competent collection of complaints and anamnesis, including family history, physical examination, endoscopic examination of the nasal cavity, rhinomanometry, skin prick tests, radiological studies, including computed tomography of the paranasal sinuses, intradermal tests, study of total and specific immunoglobulins E in blood serum, basophil activation test, nasal provocation test, nasal cytology and biopsy histology, acoustic rhinometry, nasal inspiratory peak flow testing, and nitric oxide measurements are used. Attention is also paid to laboratory and instrumental methods for the differential diagnosis of rhinitis of pseudoallergic origin; the following methods are used: ultrasound diagnostics of the hepatobiliary system, biochemical blood test, and immunological studies.

Treatment of patients with allergic rhinitis requires an integrated and interdisciplinary approach and, of course, requires differential and personalized methods taking into account etiopathogenetic mechanisms.

Russian Journal of Immunology. 2024;27(4):925-928
pages 925-928 views

Tissue pool of hypersegmented neutrophils in patients with precancerous and tumor diseases of the larynx and laryngopharynx

Kologrivova E.N., Pleshko R.I., Cheremisina O.V., Boldyshevskaya M.A., Gereng E.A., Nasibov T.F.

Abstract

The presence of neutrophils in a tumor often correlates with an unfavorable prognosis, however, there is still no clear answer about the role of tumor-associated neutrophils and the relationship of their morphofunctional features with the prognosis of the course of the disease. The aim of the study was to evaluate the structural features of tissue neutrophil nuclei in the pathological zone in patients with precancerous changes and malignant neoplasms in the larynx. Eight people with precancerous changes in the larynx, 18 patients with localized cancer of the larynx (stages II and III of the tumor process and the absence of metastases – T2- 3N0M0), and 12 patients with advanced cancer (stage III of tumor diseases and regional metastases – T3N1- 2M0) were examined. Blood slides and smear prints of tissue biopsies from three localizations were examined: 1 – zones of the pathological focus; 2 – boundaries between the pathological focus and conditionally healthy tissue; and 3 – conditionally healthy tissue. In the blood of patients with precancerous changes in the larynx and cancer patients, the main part of neutrophils was represented by cells with a 4-segment nucleus, and the number of hypersegmented forms (5 or more segments) was higher than in the blood of healthy volunteers (p < 0.002). The same type of changes in smear prints of biopsies from different areas of the pathological focus in patients with precancerous and malignant neoplasms were revealed: as they approached the pathological focus, an increase the cells with 4-5 or more segments was observed. The content of hypersegmented forms was maximum in the pathological focus. Only in patients with a widespread tumor process, neutrophils with a 4-segment nucleus dominated the immediate environment of the tumor. As the tumor spreads and metastases form, the proportion of hypersegmented cells increases in the population of intra-tumor neutrophils. It is very likely that the morphological features of tissue neutrophils in different zones of the pathological focus reflect their functional heterogeneity, and hypersegmetation of nuclei can be considered as a potential predictor of the development and progression of the tumor process.

Russian Journal of Immunology. 2024;27(4):929-938
pages 929-938 views

Comparative characteristics of the blood cytokine profile in gastritis in schoolchildren with a family predisposition to gastric cancer and peptic ulcer

Polivanova T.V., Vshivkov V.A.

Abstract

The formation of diseases of the gastric and duodenum in the adult population begins at school age. Among the leading risk factors for their formation are family predisposition (to peptic ulcer disease (PU), gastric cancer). The basis for their formation is gastritis, the course of which is actively influenced by cytokines. Aim. To study the characteristics of cytokine levels in blood serum in schoolchildren with gastritis and a family history of gastric cancer and peptic ulcer. A total of 179 schoolchildren with gastroenterological complaints were examined. All subjects underwent an endoscopic examination with biopsies taken from the antrum of the gastric and morphological confirmation of gastritis (Sydney classification). The presence of H. pylori was also determined by morphological method. The level of cytokines in the blood (IL-2, IL-4, IL-8, IL-18, IL- 1β, IFNα, TNFα) was determined by ELISA. The study found that schoolchildren with a burden of ulcer had a decreased IL-1β in comparison with children without aggravation (p = 0.005), and with children with a burden of cancer (p = 0.030). Also, IFNα was increased in schoolchildren with a burden of ulcerative disease (p = 0.001) and gastric cancer (p = 0.038). A decrease in IL-1β was found in children with aggravated ulcer disease, both with H. pylori infection (p = 0.048) and without it (p = 0.043). IL-1β plays an important role in the immune response to H. pylori infection. In addition, it is known that during H. pylori infection the level of IL-1β increases, which is accompanied by inhibition of gastric acidity. There was a decrease in IL-1β and an increase in IFNα in children with aggravated ulcer disease, regardless of the activity of inflammation. In addition, they observed an increase in TNFα (p = 0.04) with high gastritis activity (stage 2-3). In addition, in children with ulcer burden and high gastritis activity, IL-4 is increased (p = 0.018). Thus, in children with a family history of both peptic ulcers and gastric cancer, there are features of the association of specific cytokines with gastritis, as well as its activity and H. pylori infection.

Russian Journal of Immunology. 2024;27(4):939-946
pages 939-946 views

Blood cytokines in children with erosive gastritis

Polivanova T.V., Vshivkov V.A.

Abstract

Aim: To evaluate the cytokine profile of blood serum in children with erosive gastritis depending on the activity of the inflammatory process, bacterial invasion of H. pylori and family predisposition to peptic ulcer disease. Gastroscopy was performed with the collection of biopsy material from the gastric mucosa in 168 children aged 7-17 years with gastroenterological complaints. Subsequently, a morphological examination of biopsy specimens confirmed the diagnosis of gastritis in all examined patients and determined H. pylori invasion. The content of cytokines in the blood serum (IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IL-1β, IFNα, TNFα) was determined using the enzyme immunoassay method. When analyzing cytokine levels in schoolchildren infected with H. pylori, there were no differences in cytokine concentrations (p > 0.05). While in uninfected children in the presence of erosive changes, a decrease in IL-2 content was noted (p = 0.026). In individuals with a family history of peptic ulcer disease with erosive gastritis, an increase in the content of IL-8 was observed (p = 0.006), which is known to play an important role in maintaining innate immunity. Whereas, in the absence of a family predisposition, schoolchildren with erosive gastritis showed a decrease in IL-2 (p = 0.027), which is similar to the level of IL-2 in schoolchildren with erosive gastritis without H. pylori infection. IL-2 is considered an activator of the antitumor response and this property is being actively studied in patients with gastric cancer. In the context of these data, it can be assumed that in individuals with erosive gastritis, even without a family predisposition and H. pylori infection, inhibition of IL-2 synthesis is observed. What causes this influence is an open question. Thus, the variety of components of the cytokine profile involved in the regulation of the inflammatory process and the influencing negative factors create difficulties in assessing and, even more so, predicting the role and significance of changes in the content of a particular cytokine in the blood serum in children with erosive gastritis.

Russian Journal of Immunology. 2024;27(4):947-952
pages 947-952 views

Immunological indicators of the risk of the transition from chronic gastritis to gastric ulcer in adolescents

Shodieva M.S., Teshaev S.J., Navruzova S.I.

Abstract

As is known, gastric ulcer (GCC) and duodenal ulcer (duodenal ulcer) are chronic, complex-etiology diseases, the mechanism of which is based on complex transformations of nervous, hypothalamic-pituitary, hypothalamic-pituitary-adrenal and local gastroduodenal processes that lead to a change in trophism in the mucous membrane of the stomach and duodenum. In turn, the incipient ulcerative defect is a source of irritation of the enteric receptors, supporting disorders of neurohormonal regulation. Thus, the resulting “vicious circle” causes the chronic course of peptic ulcer disease. During the study of chronic diseases of gastroduodenal localization, including peptic ulcer disease, many doctrines of its occurrence have been proposed. However, the issue of the origin of peptic ulcer disease still remains insufficiently studied; approaches and tactics for managing patients with erosive and ulcerative lesions of the upper gastrointestinal tract are being developed. The aim of the study was to evaluate immunological indicators that determine the risk of chronic gastritis turning into gastric ulcer. The study included 120 children aged 14-17 years, permanently residing in the Bukhara region of the Republic of Uzbekistan. Taking into account the importance of H. Pylori in the development of HCG, patients were distributed depending on the association of HCG with H. Pylori. To study cytokines, blood tests of patients were performed to determine the titer of antibodies (IgG and IdM) to H. Pylori, immunoglobulins A, M, G in blood serum, secretory IgA in oral fluid, IL-1β, IL-10, TNFα, VEGF in the serum of patients. At the same time, blood sampling was carried out in the periods before and 3 weeks (21 days) after treatment. Thus, the study of the value of immunological blood parameters in the progression of HCG to gastric ulcer disease dictates the need to develop immunological indicators for predicting the progression of HCG to gastric ulcer in adolescents. An increase in TNFα levels indicates a high risk of developing gastric ulcer as a result of vascular damage and impaired local circulation. In the study, an established increase in the level of IL-1β indicates activation of the synthesis of proinflammatory cytokines in HCG, especially in HCG associated with H. Pylori. The use of these recommendations contributes to the monitoring of HCG, improving the effectiveness of diagnosis and the correct choice of treatment for patients with HCG, reducing mortality and disability at the same time.

Russian Journal of Immunology. 2024;27(4):953-958
pages 953-958 views

The diagnostic value of cytokines in chronic glomerulonephritis in children

Navruzova S.I., Ergasheva M.U.

Abstract

In modern clinical practice of pediatricians, the problem of timely adequate treatment of chronic glomerulonephritis (CGN) in children is of particular relevance, due to both the high prevalence of the disease and the severity of its course, the complexity of therapy and the ambiguity of the prognosis. Lesions of the urinary system in children are not only common, but also tend to grow, and often at an early age. Deterioration of the environmental background, toxic and allergic effects of drugs lead to damage primarily to the kidneys, which are the eliminating organ. The aim of the study was to study urocytokines to assess the immune response in children with HCG, depending on the association with cytomegalovirus infection. The study included 100 children aged 4-7 years, permanently residing in the Bukhara region of the Republic of Uzbekistan. At the time of the study, the patients were undergoing routine treatment in the Department of Pediatric Nephrology of the Bukhara Regional Children’s Multidisciplinary Medical Center. All children underwent general clinical (general blood test with leukoformula, general urine analysis, biochemical blood test with determination of urea, creatinine and cystatin C, immunological (TNFα, IL-18, MCP-1, IgM and IgG antibodies to cytomegalovirus infection (CMVI) in blood serum, IL-1β and IL-17A in urine) examination methods. Thus, it was found that the concentration of cystatin C in the blood serum was inversely proportional to the glomerular filtration rate in the kidneys – with a decrease in kidney function in sick children, a twofold increase was noted, that is, the accumulation of cystatin C in the blood. An increase in the concentration of IL-18 in serum and IL-1β in urine relative to the control group in CGN was an indicator of the severity of an autoimmune reaction, and a relatively low concentration of cytokines in both blood and urine in CGN with CMVI indicated suppression of the specific antiviral immunity of CMVI. It was found that an increase in serum MCP-1 by 1.4 times in group 1 and 2.9 times in group 2 of CGN with CMVI is an indicator of viral kidney damage. A significantly high concentration of IL-17A in urine in CGN with CMVI indicated local cytokine production in the kidneys and acted as an indicator of the prognosis of the outcome of CGN.

Russian Journal of Immunology. 2024;27(4):959-966
pages 959-966 views

A view of immunologic male infertility from the perspective of preserving seminal fluid homeostasis

Minasova A.A., Savochkina A. ., Nokhrin D.Y., Sharabakina K. ., Pashkina N.V., Nikushkina K.V.

Abstract

The basis of the pathogenesis of immunologic male infertility is the production of antisperm antibodies against sperm antigens by plasmocytes. Extracellular nucleic acids, among other antigens, are perceived as DAMPs. The clearance system for biological fluids is complex. Endonucleases are responsible for the utilization of extracellular DNA. Among endonucleases, DNase 1 is the most studied. Its concentration in biological fluids is higher than others. For the first time, we determined the concentration of DNase 1 in the seminal fluid of men of reproductive age. DNase 1 concentration values were compared with the level of antisperm antibodies in the ejaculate, after which the relationship between the enzyme level and standard spermogram parameters was determined. The material for the study was the ejaculate of 44 relatively healthy men of reproductive age. During spermiological analysis, macroscopic and microscopic parameters of seminal fluid were determined, the concentration of deoxyribonuclease 1 (DNase 1) in the material was determined by enzyme immunoassay, and the presence of antisperm antibodies was assessed using a direct diagnostic method – the MAR test. Statistical processing of the obtained data was carried out using analytical software PAST v. 4.06. Reference intervals for DNase 1 concentrations were calculated using the MedCalc v. 17.4 program. The relationship between spermogram parameters and DNase 1 concentration was assessed by calculating Spearman’s linear rank correlation coefficients. As a result, a negative correlation was found between the DNase 1 ratio and such ejaculate parameters as liquefaction time (rS = -0.37; p = 0.013) and viscosity (rS = -0.37; p = 0.013), as well as the level of antisperm antibodies A (rS = -0.43; p = 0.003) and G (rS = -0.33; p = 0.027), the mucous component of the ejaculate (rS = -0.37; p = 0.012) and agglutination of male germ cells (rS = -0.33; p = 0.029). According to the data obtained, the optimal level of DNase 1 is directly related to the quality of the ejaculate. Determination of DNase 1 concentration can serve as an additional diagnostic criterion for male immunological infertility. These data will expand our understanding of a man’s fertile potential.

Russian Journal of Immunology. 2024;27(4):967-974
pages 967-974 views

Dental implantation in patients with comorbid diseases: yes or no?

Labis V.V., Isakina M.O., Kozlov I.G.

Abstract

Patients with multiple pathologies are a high-risk group, which requires a personalized approach to surgical rehabilitation in dentistry. Inadequate diagnosis of clinical manifestations when a patient is in remission often leads to severe surgical complications. However, modern methods of dental implantation and rehabilitation are possible even in patients with oncology, those who underwent surgical therapy, chemo- or radiotherapy. Gilbert syndrome, one of the risk factors for post-surgery inflammatory complications, is associated with defects in bilirubin metabolism. It inhibits platelet activity. It is a genetic disease leading to a loss of liver enzyme activity and the accumulation of indirect bilirubin that can aggravate the course of other diseases in patients. In acute stages, it is characterized by jaundice of the skin, eyes, and mucosa and is followed by immunosuppression and the post-surgical complications associated with it. A patient with Gilbert syndrome was administered for surgical treatment of a chronic infection and follow-up rehabilitation via dental implantation and reconstruction of the bone. In this case, we faced Gilbert syndrome in association with polycythemia (a myeloproliferative disease in the compensation stage). In such cases, dental implantation cannot be achieved in the complex dental rehabilitation process. Such diseases require special attention from dental surgeons due to possible complications (bleeding, thrombosis, or disseminated intravascular coagulation). In this specific case, the patient belongs to the risk group, and its history, although in remission, is still a contraindication for dental surgery and dental implantation.

Russian Journal of Immunology. 2024;27(4):975-980
pages 975-980 views

Efficacy and pharmacodynamics of herbal medicine in patients with metabolic phenotype of osteoarthritis

Shirinsky I.V., Filatova K.Y., Shirinsky V.S.

Abstract

High prevalence of the metabolic phenotype of osteoarthritis (MPOA) and unsatisfactory methods of its treatment necessitate the development of novel therapeutic approaches for this phenotype of OA. Turmeric preparations have a wide range of biological activity; their use in patients with MPOA can be effective and reduce the drug burden. In the present paper, we review our own published research findings on the effectiveness and pharmacodynamics of turmeric preparations in patients with MPOA. In the two studies, we evaluated the effects of two curcumin-containing parapharmaceuticals: Epigenorm Antivir (EA) and Curcumin. Forty-one women with MFOA were included in both studies. Twenty-three patients received EA at a daily dose of 1000 mg for 12 weeks, and 18 patients received curcumin from Evalar at a dose of 1000 mg for 8 weeks. The endpoints for both studies were VAS pain, dysfunction and other symptoms of OA measured using the KOOS scale. After 12 weeks of EA treatment, there was a 2.5-fold decrease pain levels. The decrease in pain was associated with an improvement in the patient’s daily and sports activities and quality of life. These effect sizes were classified as moderate to large according to Cohen. No adverse events were observed during the period of taking EA. Clinical improvement was associated with a decrease in the content of MS individual components: low-density lipoprotein cholesterol and triglycerides. The treatment caused a decrease in the level of systemic inflammation, as evidenced by a decrease in the concentration of TNFα, histamine, IL-18, C-reactive protein, and neopterin. The concentrations of IL-10 and adiponectin increased after treatment. In another study, treatment with curcumin for 4 weeks had an analgesic effect, improved measures of function and quality of life. Clinical improvement was associated with the reductions in serum levels of a number of proinflammatory cytokines, C-reactive protein, and lipids. Thus, the results of the pilot studies evaluating efficacy, safety, and pharmacodynamics of parapharmaceuticals EA and Curcumin in patients with MFOA indicate pleiotropic effects of the interventions. The findings provide a rationale for conducting larger, controlled, blind, randomized clinical trials.

Russian Journal of Immunology. 2024;27(4):981-986
pages 981-986 views

Specific anti-toxic immunotherapy: use in medical practice and perspectives

Kozlov V.K.

Abstract

The results of use of approaches and means of antitoxic immunotherapy in medical practice are summarized: passive transfer of various variants of antibodies specific to toxic compounds, vaccination – specific active immunization with vaccines carrying determinants of the immunochemical specificity of target toxic compounds. The practical effectiveness of the known approaches of passive transfer and vaccination is associated with the ability of specific antibodies, by binding target bioactive compounds with pronounced toxicity, to change the availability of corresponding structures in the body-targets and, in the presence of a sufficient number of specific antibodies with high binding ability to the target compounds, neutralize their toxicity. In medical practice, polyspecific heterologous antisera or the gamma globulin fraction of antisera (extremely rare monoclonal antibodies of narrow specificity) are widely used for passive transfer as antidotes in the treatment of victims in order to prevent deaths and extensive necrosis of soft tissues at the site of the bite of poisonous snakes and insects. Active immunization – vaccination with appropriate antigenic drugs should create in immunized individuals a state of humoral immunity with the corresponding characteristics of antibody formation specific to the target compound. When a target toxic compound enters an immunized organism, it is also possible to neutralize its toxicity. The most successful experience in using the principles of active immunization as a technology for specific antitoxic therapy is associated with the practice of using toxoids for toxinemic infections. Specific practical techniques used to achieve the effectiveness of possible approaches to specific antitoxic immunotherapy in the form of passive transfer of specific antibodies or their fragments are considered: to combat lethal infections in the pathogenesis of which the toxic effects of bacterial exotoxins are significant; when treating victims of snake and insect bites, exposure to poisons of marine organisms, algae and plant toxins; in the treatment of severe intoxication with certain low molecular weight toxic substances: digoxin, colchicine, tricyclic antidepressants. The most successful experiences of using the principles of active immunization as a technology for specific antitoxic therapy, based on the use of toxoids with specificity for diphtheria, tetanus, botulism, cholera, typhoid fever, dysentery, gas gangrene and other toxinemic infections, are also considered. The fairly high immunogenicity of toxoids with the possibility of activating both constitutional and adaptive immunity has become the basis for their use as macromolecular carriers of hapten analogues of narcotic substances – a promising direction in drug addiction, in the implementation of which a number of experimental molecular and combined vaccines of opiates, methamphetamine, cocaine, and nicotine. This variant of practical efforts in medicine can be regarded as a new direction of specific antitoxic immunotherapy – an option to combat drug addiction by vaccinating drug addicts.

Russian Journal of Immunology. 2024;27(4):987-994
pages 987-994 views

VDR gene polymorphisms rs731236 and rsS2228570 affect vitamin D levels in people of the Kaliningrad region

Bograya M.M., Vulf M.A., Safiullina L.A., Paskidov D.V., Shnar V.A., Gazatova N.D., Mikhailova L.V., Litvinova L.S.

Abstract

Vitamin D is an essential micronutrient that is involved in numerous biological processes. It not only keeps bones healthy, but also has a protective effect on the cardiovascular system, the pancreas and fatty tissue. Around 50% of the world’s population suffers from vitamin D deficiency or insufficiency. The prevalence of these diseases is significantly higher in obese people, regardless of age and place of residence. The presence of polymorphisms in the VDR gene (vitamin D receptor) can explain individual differences in the concentration of vitamin D 25(OH) in blood serum. Of particular interest are the effects of the polymorphisms rs731236 and rs2228570 on vitamin levels. Thus, the VDR polymorphism rs731236 is a synonymous substitution, whereas the polymorphism rs2228570 is a non-synonymous substitution. The article investigated the polymorphisms of the VDR gene rs2228570 (T/C), rs731236 (T/C) and determined their association with blood vitamin D levels in people from the Kaliningrad region with different body mass index (BMI). The material for the study was venous blood taken in the morning on an empty stomach from 232 people (mean age 50±13.5 years, 103 men and 129 women). The vitamin D content in the blood was determined by ELISA and the polymorphisms of the VDR gene were analyzed by PCR.

In individuals with a BMI > 30 kg/m2, changes in the lipid profile and liver function tests were recorded. The vitamin D level did not depend on the BMI of the study participants. Significant changes in blood vitamin D levels were found depending on the distribution of the VDR genotype. Vitamin D levels were higher in individuals with the CC genotype than in the TT and CT genotypes of the rs2228570 polymorphism and did not depend on BMI. In contrast, the presence of the rs731236 polymorphism in the VDR gene is associated with BMI. In obesity, vitamin D levels are therefore only reduced in people with the TT genotype of the rs731236 polymorphism, but not in people with the CC and TC genotype.

Russian Journal of Immunology. 2024;27(4):995-1000
pages 995-1000 views

Phagocytic activity of neutrophil blood granulocytes in children with chronic non-specific lung diseases with post-inflammatory pneumofibrosis

Evseeva G.P., Knizhnikova E.V., Abdulina N.O., Pichuginа S.V., Chaika M.S.

Abstract

One of the reasons for the development of chronic forms of lung diseases and pneumofibrosis as a pathological outcome of this inflammation may be an insufficient immune response. The key position belongs to neutrophilic granulocytes. Given the importance and renewed interest in neutrophils as tools for regulating immunity, leading to the progression of the fibrous process in children with CKD is an urgent problem. The purpose of the study was to study the phagocytic activity of blood neutrophils as an important component of innate immunity in patients with CNLD. Seventy children with CNLD with focal or segmental post-inflammatory pulmonary fibrosis were examined. Of these, 27 were children with progression of PPF (main group) and 43 children with PPF without progression (comparison group). The controls were the indicators of 23 healthy children, comparable by gender and age. The studies were carried out during clinical remission. The phagocytic activity of neutrophils (PНAN), phagocytic number (PN), spontaneous and stimulated NBT test were determined. The stimulation index of the NBT test (NBTst-NBTsp) was calculated. The mitochondrial membrane potential was determined using a BD FACS Calibur cytometer (USA) (BD Pharmigen, USA).

PN in children with chronic heart disease with progressive PF was significantly reduced in comparison with patients in the comparison group and with the control group. The PHAN in children with CKD in both groups was within the standard values, however, it was lower than in the control group. The activity of the spontaneous HBT test in children of the main group was 1.7 times higher than in children in the comparison group and 3 times higher than in children from the control group. However, the stimulation index in the main group was significantly lower than in the control group. An increase in cells with a reduced membrane potential of granulocyte mitochondria was revealed in children of the main group compared with the control group. Children with CKD with the progression of fibrosis processes develop changes in the functional and metabolic activity of peripheral blood neutrophils typical for an inflammatory reaction, characterized by an increase in oxygen-dependent and a decrease in phagocytic cell activity.

Russian Journal of Immunology. 2024;27(4):1001-1008
pages 1001-1008 views

The paradigm of possibilities leading to the formation of autoimmune and infectious phenotypes of common variable immune deficiency

Sizyakina L.P., Andreeva I.I., Danilova D.I.

Abstract

The term variable in the definition of CVID is associated with the heterogeneity of the genetic nature and clinical manifestation of this variant of PI. Deciphering of the mechanisms or identifying biomarkers of clinical heterogeneity may be important in the timely diagnosis and prognosis of the course of CVID. The purpose of the study was to identify distinctive features in the parameters of the innate and adaptive immune response of the patients with infectious and autoimmune manifestations of CVID in remission and clinical manifestation. Fifteen patients, 11 women and 4 men with an average age 39.7±11.7 years were examined, and they were divided into two subgroups depending on clinical verification: infectious phenotype (10 people) and autoimmune phenotype (5 people). In the absence of clinical signs of activation of autoimmune pathology or exacerbation of chronic infectious processes, peripheral blood monocytes became the application point of distinctive values. An increase in the number of TLR9-expressing monocytes has been shown in patients with autoimmune clinical verification of CVID. The differences in the parameters of the immune status of patients conducted during the period of clinical manifestation consisted of a decrease in the relative content and absolute number of T regulatory lymphocytes, and an increase in the number of monocytes containing TLR9, TLR2 and HLA-DR in patients with an autoimmune phenotype relative to the subgroup with infectious manifestation. The data obtained reflect the involvement of the immunoregulatory potential of the immune system in the clinical manifestation of primary immunodeficiency, even under the conditions of pathogenetic substitution therapy. The evidence of the stated position is a decrease in immunosuppression in autoimmune manifestation due to a decrease in the number of peripheral T-regulatory cells and a smaller proportion of monocyte cells belonging to the M2 suppressive category. Attention is also drawn to the increased potential of primary response to patterns of various nature in autoimmune manifestation due to an increase in the number of monocytes expressing Toll-like receptors of various specificity. The presented results can be proposed as a diagnostic and prognostic indicator of the difference in clinical phenotypes of CVID.

Russian Journal of Immunology. 2024;27(4):1009-1016
pages 1009-1016 views

A novel immunopharmacological biocompound

Zabokritskiy N.A.

Abstract

The publication is devoted to topical issues of experimental study of new biocompounds, based on the creation of a consortium of biological composite compounds – biological active substances (metabiotics) produced by strains 59T and 60T of saprophytic compounds of the genus Bacillus subtilis. These strains are very promising for the creation of hepatopicts, new medicinal substances, in the creation and development of a new pharmacological class of hepatoprotectors. Previous studies have shown the safety and hepatoprotective effect of biologically active drugs. It is worth noting that the very effective compounds are the produced biologically active substances – metabolites of bacterial origin, on the basis of which it seems appropriate to create a new class of drugs – metabiotics. The absence of vegetative probiotic cells in such compounds will reduce the additional immune load on the body. The combined use of these compounds provides a potentiated pharmacological effect. In this regard, it seemed appropriate, under the conditions of modeling toxic liver damage by carbon tetrachloride, to conduct an experimental assessment of the immunotropic effect of biologically active substances (BAS) on laboratory animals in order to confirm the effect on cellular factors of immunity. The purpose of the study was to study the effect of the combined use of dietary supplements produced by Bacillus subtilis microorganisms on indicators of cellular immunity in laboratory animals with toxic liver damage. Acute toxic hepatitis was reproduced in white laboratory rats with repeated intragastric administration of carbon tetrachloride. The comparison drug was a registered hepatoprotective drug – ursosan. The immunotropic effect was assessed using factors such as: phagocytic activity of macrophages and neutrophils (FA), NBT test, quantitative assessment of antibody-forming cells, T and B lymphocytes. As a result of the studies performed, reliable data were obtained on an increase in the number of T and B lymphocytes, antibody-forming cells, as well as an increase in FA, which confirms the activation of all parts of cellular immunity in conditions of acute toxic liver damage. The data obtained allow us to recommend the studied biocompound for the creation of new drug candidates of microbiological origin, hepatoprotective agents with immunotropic effects.

Russian Journal of Immunology. 2024;27(4):1017-1020
pages 1017-1020 views

Evaluation of the preventive effectiveness of russian influenza vaccines in the epidemic seasons of 2018-2021

Erofeeva M.K., Buzitskaya Z.V., Shakhlanskaya E.V., Pisareva M.M., Stukova M.A., Lioznov D.A.

Abstract

Monitoring the effectiveness of influenza vaccines annually enables the development of measures aimed at decreasing influenza incidence, hospitalization, and mortality rates. The epidemiological effectiveness of several Russian domestic influenza vaccines was evaluated in St. Petersburg in the 2018-2021 epidemic seasons. Male and female participants (N = 6912) aged 18-23 were monitored from 2018 to 2021. Sovigripp, Grippol Plus, Ultrix, and Ultrix Quadri inactivated influenza vaccines were used for immunization. In 2018-2019, when the vaccine strains fully matched the circulating influenza viruses, prophylactic vaccination resulted in a 2.7 to 7.1-fold reduction in influenza cases. The protective effectiveness of the vaccines against influenza and acute respiratory infections (ARIs) totalled 52.4%, reaching 73.0% effectiveness against influenza after laboratory confirmation. In the epidemic season 2019-2020, when the circulating viruses and vaccine strains did not fully match, the incidence of influenza and ARIs reduced twice due to vaccination; the total vaccine effectiveness against influenza and ARIs amounted to 50.0%. The Grippol Plus, Ultrix, and Ultrix Quadri vaccines proved to be the most effective, demonstrating a total effectiveness of 70.6%-75.0% and a 65.5%-83.5% effectiveness against influenza A and B. In the 2020-2021 epidemic season, no data on the preventive effectiveness of the influenza vaccines could be obtained due to the outbreak of COVID-19 and the absence of detectable influenza virus shedding in the study participants. The results obtained are consistent with WHO experts’ estimates which indicate that modern influenza vaccines reduce the incidence of influenza in adults by 70-90% if the vaccine strains match the circulating virus strains.

Russian Journal of Immunology. 2024;27(4):1021-1028
pages 1021-1028 views

Use of mobile communication technology to overcome vaccine skepticism

Aleshina L.V., Gamova I.V., Girsha A.Y., Belikova A.V., Aleshin D.V.

Abstract

Despite significant advances in clinical medicine, infectious diseases and their prevention remain the leading problem of our time. Low literacy of the population reggarding immunization, combined with high activity of the anti-vaccination movement, creates unhealthy skepticism about immunoprophylaxis and the risks of epidemics.

The work uses theoretical analysis of literature, methods of anonymous questionnaires of students of medical and non-medical specialties, methods of statistical and bioinformatics data processing, and modern internet technologies: the platform of the social network “Vkontakte” and the program for creating a chatbot “Senler”.

The analysis of commitment to vaccination of medical and non-medical students showed that 65.8% to 96.2% of respondents have a positive attitude to preventive health measures. From 1.9% to 6% believe the disease is easier to treat than to prevent, and almost 30% of respondents do not think about prevention and diseases in general, considering themselves young. Almost 10% of non-medical students (1 group) consider vaccination useless, 8.4% dangerous for immunity, 18.3% know nothing about vaccinations and cannot compare the benefits of vaccination with the risk of infectious pathology. In order to form medical literacy of the population, including in strategic issues of preserving the health of the nation, the team of authors developed and implemented through the social network “Vkontakte” chatbot “Vaccine and point” containing up-to-date information about vaccines, methods multiplicity and age features of their use. People [n = 156] used the chatbot during the month of work, noting its high informational value, motivating to vaccination.

Analysis of commitment to vaccination of students of medical and non-medical specialties showed an insufficient level of trust in domestic preventive medicine, which forms an unhealthy attitude to vaccine prevention. Insufficient vaccine coverage creates real threats to the spread of infectious diseases at the population level. Developed and implemented in real practice, the “Vaccine and point” chatbot is an effective tool for increasing the knowledge of compatriots about the real possibilities of protection against the main vaccine-controlled infections and an additional attempt to overcome anti-vaccination skepticism.

Russian Journal of Immunology. 2024;27(4):1029-1034
pages 1029-1034 views

The results of vaccination against novel coronavirus infection in adolescents with allergic diseases

Andreeva N.P.

Abstract

Novel coronavirus infection requires analyzing its course in patients with allergic diseases. Patients with atopic allergic diseases remain insufficiently studied with regard to the peculiarities of the course of both the underlying allergic disease and infectious processes caused by viruses and bacteria. Epithelial cells in bronchial asthma do not respond sufficiently to interferons, suggesting that SARS-CoV-2 infection may suppress spontaneous upregulation of angiotensin-converting enzyme expression, which ultimately reduces disease severity, but at the same time makes patients with allergic atopic diseases susceptible to other viral infections. The results obtained indicate statistically significant differences in the formation of anti-RBD IgG antibodies to SARS-CoV-2 between the group of adolescents with bronchial asthma vaccinated against a new coronavirus infection and those not vaccinated against it. During the follow-up period after 6 months, a statistically significant increase in anti-RBD IgG titer to SARS-CoV-2 due to novel coronavirus infection was observed among the unimmunized children. Clinical parameters indicated a favorable course of atopic process and control of bronchial asthma exacerbations in adolescents who received vaccination against both new coronavirus infection and influenza, while those who did not receive vaccination against these viral infections had bronchial asthma exacerbations due to respiratory infection. Also among patients with bronchial asthma who received influenza vaccination, there were no cases of influenza A and bronchial asthma exacerbations due to respiratory infections. In this regard, influenza vaccination is an important intervention to maintain control of asthma exacerbations. It is noteworthy that no new coronavirus infection was reported among vaccinated adolescents within a year after immunization. At the same time, 6 months after vaccination against a new coronavirus infection, we observed a statistically significant increase in antibody levels in unvaccinated adolescents, indicating the presence of high viral neutralizing activity. Vaccination against novel coronavirus infection in patients with bronchial asthma may be considered a possibility.

Russian Journal of Immunology. 2024;27(4):1035-1040
pages 1035-1040 views

New concept for the prevention of acute respiratory infections

Borisov A.G., Tikhonova E.P., Kostromina R.A., Anisimova E.N., Sadowsky I.S., Bronnikova E.P., Peretyatko O.V., Savchenko A.A.

Abstract

Medical personnel and family members of patients with acute respiratory diseases (ARD) are at increased risk of infection during epidemics or pandemics. In this regard, it is necessary to develop and implement accessible preventive measures. The aim of the study was to evaluate the effectiveness of the use of IFNα-2b for the prevention of acute respiratory viral infections in persons located at the source of infection (medical personnel and members of their families).

Patients (n = 31) with acute respiratory infections and 117 people from their environment (family members in constant contact with patients) were examined. The subjects underwent a clinical examination and laboratory tests a clinical blood test and a study of the content of the main populations and subpopulations of lymphocytes in the blood. Persons in contact with ARD patients were divided into three groups: persons who received the drug “Grippferon” for 7 days; persons who received the drug “Grippferon” in a prophylactic dose for 7 days; persons in contact with patients with ARD but who have not received the drug “Grippferon”.

When assessing the state of the immune system, it was found that the most common type of immune reaction in patients and their people around was activation of innate immunity (48.39% and 66.67%, respectively). At the same time, immunodeficiency in the group of patients with ARD was detected much more often than in persons in contact with them. In addition, patients were more likely to have monocytosis (1.4 times), T lymphocytopenia (2.1 times) and an increase in the number of regulatory T lymphocytes (7.6 times). More than 50% of those examined in both groups showed an increase in the number of NK cells in the blood. An examination of persons in contact with patients with ARD after 7 days of using the “Grippferon” in different doses revealed that the lowest frequency of acute respiratory viral infections symptoms was found in the group receiving IFN at a therapeutic dose. In the group receiving IFN in a prophylactic dose, the frequency of acute respiratory viral infection (ARVI) symptoms was detected in almost 40% of those examined. More than 80% of people from the group who did not receive the “Grippferon” had symptoms of ARVI after a week of contact with patients with ARD.

Thus, the use of IFN in therapeutic doses during the epidemic for persons in contact with patients is proposed as a new concept for the prevention of ARD.

Russian Journal of Immunology. 2024;27(4):1041-1048
pages 1041-1048 views

Study of the state of humoral immunity to COVID-19 in Arkhangelsk residents

Krieger E.A., Samodova O.V., Samoylikov R.V., Shchepina I.V.

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 has affected healthcare, society and the economy in all countries, including Russia. Several vaccines have been created as the method for COVID-19 prevention. One of the most widespread vaccines in Russia, which has received international recognition, is the Gam-COVID-Vac (Sputnik V) vaccine and its variant Sputnik Light, which represents its first component. This vaccine, like similar vaccines in many countries, was used during the pandemic. The purpose of this work is to study the humoral immunity status of Arkhangelsk city residents and the effect of vaccination on them. Adult residents of Arkhangelsk [N = 281] were enrolled in the randomized study. Samples from vaccinated people and the control group were collected for the study in October 2022.The median from the time of last vaccination/booster to sample collection was 10 months. The samples were tested for the level of IgG to the receptor-binding domain of the SARS-CoV-2 S protein. The work assessed the humoral immunity status among residents of Arkhangelsk. It was shown that in October 2022 high IgG values were recorded among the people in the studied groups, most likely caused by contact with the SARS-CoV-2 virus. The humoral immunity status of unvaccinated residents, for those who have had COVID-19 and those who have not, is described; a significant increase in the level of IgG among those vaccinated compared to unvaccinated people is shown, despite the fact that the average time after vaccination was more than 10 months. A comparative analysis of IgG levels among different age groups was carried out. The study found no difference in post-vaccination antibody levels among people over 65 years old compared to younger age groups. Also there were no statistically significant differences in antibody levels among unvaccinated people over 65 in respect to younger age groups.

Russian Journal of Immunology. 2024;27(4):1049-1056
pages 1049-1056 views

Features of proinflammatory activation of macrophages in patients with rheumatoid arthritis and systemic lupus erythematosus

Bogatyreva A.I., Kiseleva D.G., Cherednichenko V.R., Markina Y.V., Kirichenko T.V.

Abstract

Autoimmune rheumatic diseases (ARDs) are chronic pathological conditions that arise from an abnormal immune response and are accompanied by systemic inflammation. The most common ARDs include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). The exact pathogenesis of ARDs remains unclear, but the complex influence of genetic, immunological and external environmental factors leads to the occurrence and further progression of ARDs. It has been shown that the cause of chronic inflammation may be proinflammatory activation of macrophages, in which an increase in the secretion of cytokines is observed. The aim of this study was to evaluate the inflammatory response of macrophages in patients with RA, SLE and SSc. Materials and methods. The study included 143 participants: 47 patients with RA, 45 patients with SLE, 34 patients with SSc, and 17 people without ARDs and other chronic diseases. Isolation of a primary culture of monocytes was carried out by centrifugation in a ficoll gradient using magnetic separation from the whole blood of study participants. Lipopolysaccharide (LPS) was added to stimulate cells along the proinflammatory pathway. Cell cultivation was carried out for 24 hours. Determination of basal and LPS-stimulated secretion of IL-8 by macrophages was carried out in the culture fluid using an enzyme-linked immunosorbent assay (ELISA). Proinflammatory activation of macrophages was calculated as the ratio of LPS-stimulated and basal IL-8 secretion. Research results. Basal secretion of IL-8 by macrophages was statistically significantly higher in the groups of patients with RA and SSc compared with the SLE and control groups. LPS-stimulated secretion of IL-8 by macrophages in the SSc group had statistically higher values compared to the RA and SLE groups. Proinflammatory activation of macrophages was reduced in the group of patients with RA compared to patients with SLE and the control group, and was also statistically significantly lower in patients with SSc compared to the control group.

Russian Journal of Immunology. 2024;27(4):1057-1064
pages 1057-1064 views

Some parameters of the immune system in women with hyperandrogenism

Yuldashev U.K., Muzafarova S.A.

Abstract

The article is dedicated to studying certain parameters of the immune system, which holds great significance in obstetrics and gynecology. Examining immune system parameters allows for identifying disruptions in reproductive-aged women with hyperandrogenism, which holds crucial practical implications. The authors conducted an immunological study of women with hyperandrogenism and women without this pathology. The aim of the study was to investigate the immune system status in women suffering from hyperandrogenism. Materials and methods of the study: 58 reproductive-aged women diagnosed with hyperandrogenism, under observation at the Women’s Health Center “AyolCare” in Tashkent, were examined. Comprehensive clinical and laboratory examinations were conducted for all women. The control group comprised 35 practically healthy reproductive-aged women. The obtained results indicate that women with altered hormonal balance, including those with hyperandrogenism, experience specific changes in the immune system. The conducted research revealed that the levels of T lymphocytes and T helper/inducer cells decrease, while the number of T killer cells, CD25+ cells (carrying IL-2 receptor), and CD95+ cells (carrying apoptosis signaling receptor) increases. The elevated levels of CD95+ cells indicate increased activation of apoptosis processes, which serve as a protective function of T killer cells. This increase in lymphocyte activation is likely associated with elevated levels of mature activated macrophages and a range of cytokines they produce, which directly stimulate lymphocytes. The detected imbalance in immunological parameters likely indicates that in hyperandrogenism, either the elimination of activated clones of T helper cells is absent or disrupted, which usually leads to the formation of immune response suppression. The increase in the number of activated clones of T lymphocytes is observed in the decreased process of their apoptosis, which is likely intensified by the influence of androgens.

Russian Journal of Immunology. 2024;27(4):1065-1070
pages 1065-1070 views

Brown algae of the White Sea as a promising source of fucoidan for increasing resistance in laying hens

Bakhta A.A., Karpenko L.Y., Nikonov I.N.

Abstract

The purpose of this study was to evaluate the effect of a feed additive from fucus algae on resistance indicators of laying hens in industrial poultry farming conditions. In the algae F. vesiculosus and A. Nodosum, it was revealed that the mass fraction of fucoidan in terms of a.d.w. is 3.92±0.12%.When assessing the effect of using a feed additive from fucus algae on resistance indicators of laying hens, it was revealed that it has an effect on white and red blood parameters, leukogram and phagocyte activity. In chickens of the experimental group, there was a tendency towards an increase in the number of erythrocytes, an increase in the color index, a tendency towards a decrease in the number of leukocytes relative to the increase in the control group, while the indicators were within the reference values, after 30 days of using the additive – in the experimental group the proportion of pseudoeosinovils increased by 50% and the proportion of lymphocytes decreased by 6% compared to the control group. After 60 days of using the supplement, this trend continues: the proportion of pseudoeosinophils increased by 22% and the proportion of lymphocytes decreased by 4% in the experimental group relative to the control group. In our opinion, this indicates a normalization of the ratio of leukocyte forms in the experimental group, and, consequently, the immune status. In addition, in the experimental group relative to the control group, there was a significant decrease in the number of eosinophils by 67%, which may indicate a lower allergic reaction of the body’s immune system. Indicators of blood phagocytosis significantly changed after 60 days of use: in the experimental group, phagocytic activity increased by 23%, which indicates a higher ability of leukocytes in the experimental group to absorb foreign bacteria, and, consequently, stronger cellular immunity compared to the control group. Thus, the use of a feed additive from fucus algae for laying hens containing fucoidan in an amount of 3.92±0.12% helps to normalize the ratio of leukocyte forms and increase blood phagocytosis rates, which significantly increases resistance in laying hens.

Russian Journal of Immunology. 2024;27(4):1071-1076
pages 1071-1076 views

The kisspeptin effects on the thymic regulatory cell compositions (Th17, Treg, iNKT) in vitro

Orlova E.G., Loginova O.A., Gorbunova O.L., Shirshev S.V.

Abstract

The peptide hormone kisspeptin, produced by neurons of the hypothalamus anterior zone, is a key regulator of the gonadostat formation and reproductive function, and has immunoregulatory activity. During pregnancy, kisspeptin is produced by the placenta, presents in the peripheral blood and affects on immune cells that express specific receptors for the hormone, including thymus cells. However, the kisspeptin effects on thymopoiesis during pregnancy have not been studied. The purpose of the work was to study the kisspeptin effect on the thymic regulatory cell composition in vitro. Thymocytes were cultured for 72 hours with kisspeptin at a concentration (9.6 pM) characterizing its maximum level in the peripheral blood during pregnancy, in the presence of CD3/CD28-activating particles and further assessed the regulatory cell composition and Ki-67 and Bcl-2 expression by flow cytometry. The percentage of T regulatory lymphocytes (Treg) was assessed as the percentage of CD4+CD25+FoxP3+ cells; T helper cells producing interleukin17 (Th17), as a percentage of CD4+IL-17A+RORγt+ cells; invariant T lymphocytes with natural killer functions(iNKT), as a percentage of CD3hiVa24Ja18+ cells in thymocyte culture. Dexamethasone (10-6M) was added to induce apoptosis. The effect of kisspeptin-primed thymic plasmacytoid dendritic cells (pDCs) on the regulatory cell composition (Th17, Treg, iNKT) in thymocyte culture was assessed. Thymic pDCs isolated by immunomagnetic separation were cultured for 24 hours with kisspeptin, and then intact autologous thymocytes were added in a ratio of 1:10 and cultured for another 72 hours. The thymocyte incubation of with kisspeptin did not affect the Tregs, iNKT and Th17 percentage in vitro, as well as the expression of Ki-67 and Bcl-2 in these cells. Under dexamethasone influence, the Bcl-2+Th17 percentage in thymocyte cultures with kisspeptin was increased. The Th17 percentage was increased in cultures of kisspeptin-primed pDCs with thymocytes, while the Treg and iNKT number did not change. It can be concluded that kisspeptin has regulatory effects on the Th17 percentage in thymocyte culture in vitro, mediating its effects by influencing thymic pDCs. And kisspeptin acted directly on thymocytes, increases the resistance of thymic Th17 to dexamethasone-induced apoptosis. The obtained results expand our understanding of the hormonal regulation of regulatory cell balance during pregnancy.

Russian Journal of Immunology. 2024;27(4):1077-1084
pages 1077-1084 views

Immunocorrective effects of Tricor fenofibrate in the treatment of the early and intermediate stages of age-related macular degeneration

Balatskaya N.V., Kulikova I.G., Eremeeva E.A., Andryushin A.E.

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment, blindness and disability in the elderly. Treatment of end-stage AMD is extremely limited and requires invasive interventions. Currently, there is an active search for remedies aimed at preventing the degenerative process in the retina in the early stages of the disease. AMD is a multifactorial pathology, has common mechanisms with diseases associated with aging, metabolic shifts and hemodynamic disorders. The study of the effects of drugs already used to correct these disorders in the general clinic may also be of interest to ophthalmologists. The aim of the work was to study the dynamics of inflammatory markers of activation of the vascular endothelium and cytokines of the immune response in the tear fluid (TF) of patients with initial and intermediate stages of AMD against the background of the use of Tricor fenofibrate. 65 people were examined, divided into three groups according to the AREDS classification: group I – 20 people with early AMD (AREDS2), group II – 16 patients with intermediate AMD (AREDS3), 29 healthy elderly people without ophthalmopathology entered the age control group (AREDS1 – risk group). Patients of groups I and II received Tricor at a dose of 145 mg once a day for 9 months. Tear fluid (TF) was taken twice: before and immediately after the completion of the course of treatment. The determination of sICAM-1, sVCAM-1, sE-, sP-selectin and MCP-1/CCL2 in CS was performed by flow cytometry using a self-constructed multiplex panel from compatible simplex test kits Human FlowCytomixTM Simplex (Bender MedSystem GmbH, Germany); IL-1β, IL-2 IL-6 TNFα was determined within the framework of the Human Flow CytomixTM 15 Flex system (Bender MedSystem GmbH, Germany). Data processing was performed in the FlowCytomix Pro v 6.0 package (Bender Med Systems GmbH, Germany). According to the results of the study, a significant effect of Tricor fenofibrate was found on the initially high levels of local production of IL-1β, IL-2, IL-6, MCP-1/CCL2 and sICAM-1 in the AREDS2 group, which indicated a direct anti-inflammatory, vasoprotective effect in the treatment of the initial stage of AMD; a similar effect of the drug, but less pronounced, noted in the AREDS3 group. The ophthalmological examination data also indicated stabilization of visual functions and the clinical picture of the fundus, improvement of intraocular blood circulation in patients of the main groups. Thus, the use of Tricor can help prevent the degenerative process in the retina in the early stages of AMD development.

Russian Journal of Immunology. 2024;27(4):1085-1090
pages 1085-1090 views

Morphological changes in purulent wound defect of the oral mucosa when using a non-woven polymer membrane with vancomycin (experimental study)

Sagdullaeva S.A., Varakuta E.Y., Shtyr A.V.

Abstract

Currently, the problem of effective treatment of purulent wounds of the oral mucosa is relevant, scientists are improving dressing materials, creating new coatings. The study tested for the first time a non-woven polymer membrane from a copolymer of vinylidene fluoride with tetrafluoroethylene with Vancomycin, presumably which will meet the requirements of an ideal dressing material.

The purpose of the study is to determine the effect of a non-woven polymer membrane with Vancomycin on the regeneration of a purulent wound defect of the oral mucosa in experiment.

35 white Wistar rats were divided into three groups: first group (n = 15), in which the wound defect was left open according to the standard procedure of the wound process in the oral cavity; second group (n = 15), in which the wound defect was covered with a non-woven polymer membrane with Vancomycin; third group (served as control group), in which the rats had intact oral mucosa (n = 5). Tissue samples were collected from the area of the purulent wound on the 3rd, 7th and 14th days of the study and histological sections were prepared using a standard procedure. The indicators were calculated using the AxioVision SE64 Rel program. 4.9.1: area of loose fibrous connective tissue (%), cellular infiltration (%), granulation tissue (%).The statistical analysis of the obtained data was performed using Mann–Whitney and Wilcoxon tests in Statistica 8.0 (StatSoft, USA) software. Differences were considered statistically significant at p < 0.05.

It has been established that the non-woven polymer membrane from a copolymer of vinylidene fluoride with tetrafluoroethylene with Vancomycin has a beneficial effect on the regeneration of the oral mucosa in the postoperative period and reduces scar changes in the later stages of healing.

Russian Journal of Immunology. 2024;27(4):1091-1096
pages 1091-1096 views

Indicators of the cytokine profile and standard immunogram in the controlled and uncontrolled course of bronchial asthma in children

Suprun E.N., Suprun S.V., Kozlov V.K., Galyant O.I., Evseeva G.P.

Abstract

Bronchial asthma in children is a multifactorial disease, but it is based on atopic inflammation, which is the focus of the main methods of research and therapy of this pathology. However, if we evaluate not only the fact of the appearance of bronchial asthma in a particular patient, but also consider its course in more detail, and especially the possibility of achieving control over the disease, then indicators of not only atopic inflammation, but also local inflammation in general, acquire great influence, which is one of the reasons for the continuing high percentage of uncontrolled and partially controlled course bronchial asthma in children.

The purpose of this work is to identify changes in cytokine status indicators and immunograms – markers of the risk of uncontrolled bronchial asthma.

167 patients with bronchial asthma were examined, who, based on a standard clinical and instrumental examination, according to the criteria of clinical recommendations, were divided into two groups – controlled (70 people) and partially controlled and uncontrolled (97 children). All of them had their cytokines and IgA, IgM, IgG, IgE levels determined, in blood serum by ELISA, subpopulations of lymphocytes by flow cytometry, indicators of neutrophilic phagocytosis by light microscopy.

In the group with uncontrolled asthma, the following significant differences were noted: a decrease in the level of IL-7, IL-9 and an increase in IL-8, there is also a higher level of B lymphocytes, IgE and IgM, and a lower level of IgA, similar changes, but less pronounced, were previously detected in other studies when comparing patients with bronchial asthma and conditionally healthy, as well as mild and severe course diseases. There were no significant differences in the other studied indicators.

It is noteworthy that the greater influence on the control of the disease in bronchial asthma is not exerted by atopic cytokines responsible for the very fact of atopic inflammation, but by cytokines of general inflammation, such as IL-7, IL-8, IL-9, regulating the severity of inflammation in general, the role of IL-8 as a cytokine of granulocyte chemotaxis regulating local inflammation is especially interesting.

Russian Journal of Immunology. 2024;27(4):1097-1106
pages 1097-1106 views

Alterations in expression of TLR2 and TLR4 during successful and pathological aging

Khasanova E.M., Grechenko V.V., Gromova T.V., Skhodova S.A., Gankovskaya L.V.

Abstract

The generally accepted theory of aging is the theory of inflammaging. The leading role in its development is played by the mechanisms of innate immunity. Key receptors of innate immunity are TLRs. The patterns of age-related changes in the functioning of the TLR system remain the subject of study. The purpose of the work is to study the expression of TLR2 and TLR4 receptors in peripheral blood cells of centenarians and elderly people at the level of genes and surface molecules.

The study analyzed the expression of genes and molecules TLR2 and TLR4 in young donors (n = 50), elderly people (n = 50) and centenarians (n = 100). Analysis of TLR2 and TLR4 gene expression was carried out using RT-PCR. Determination of surface expression of TLR2 and TLR4 was carried out using flow cytofluorimetry.

This study is the first to analyze the age-related dynamics of expression of genes and molecules TLR2 and TLR4. It was revealed that in groups of elderly patients and long-livers, TLR2 expression is increased both at the gene and on the cell surface, compared to young donors. In contrast, TLR4 expression decreased with age. Studied groups of patients were divided depending on the aging phenotype into two subgroups: successful and pathological aging. In elderly individuals, TLR2 is increased in both phenotypes, while TLR4 is decreased in the pathological aging. In the group of centenarians with a pathological aging, a decrease in both TLR2 and TLR4 is observed, compared with young. In long-livers with successful aging, an increase in TLR2 expression was observed at the gene and protein level and TLR4 expression was comparable to the group of young individuals.

Identified changes in the expression of TLR2 and TLR4, observed in different age groups, can be considered as markers of various aging phenotypes.

Russian Journal of Immunology. 2024;27(4):1107-1114
pages 1107-1114 views


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