Russian Journal of Immunology

Peer-review quarterly medical journal.





Founded in 1996.

“Russian Journal of Immunology” is a scientific and educational journal in the field of fundamental and clinical immunology, the purpose of which is to promote the scientific achievements of fundamental and clinical immunology for various fields of medicine, publish reviews, lectures, articles by leading domestic and foreign experts in the field of fundamental and experimental immunology, clinical immunology, allergology, immunodiagnosis and immunotherapy of infectious, allergic, autoimmune and oncological diseases.

The journal is distributed throughout the territory of the Russian Federation and CIS countries. The journal is included in the register of subscriptions:  in the catalog "The Russian Press" - 15590.


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Types of accepted articles

  • reviews
  • systematic reviews and metaanalyses
  • original research
  • clinical case reports and series
  • letters to the editor
  • short communications
  • clinial practice guidelines


  • in English and Russian
  • quarterly, 4 issues per year
  • continuously in Online First
  • with NO Article Processing Charges (APC)
  • distribution in Open Access with the Creative Commons Attribution 4.0 International License (CC BY 4.0))



Russian Journal of Immunology has been transferen to the Eco-Vector online publishing platform

Posted: 19.02.2022

From February 2022, the Russian Journal of Immunology has been transferen to the Eco-Vector online publishing platform. We would like to thank the Eco-Vector employees for prompt and high-quality content transfer. The journal archive and all services of the electronic editorial system are active and functional. We look forward to a long and fruitful cooperation!

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Current Issue

Vol 26, No 4 (2023)

Cover Page

Full Issue

Forum Sochi 2023

Immunobiology of lymphotoxin: role in a mouse model of multiple sclerosis
Gogoleva V.S., Drutskaya M.S., Nedospasov S.A.

Complex immunobiology of lymphotoxin (LTα) is due to multiple modalities of signal transduction, involving a soluble homotrimer and membrane-bound heterotrimers that engage at least three different receptors. While LTα is crucial for the formation and maintenance of secondary lymphoid organs, its overproduction is observed in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Initially, LTα was considered pathogenic in the development of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, as demonstrated by the resistance of mice with genetic LTα inactivation to EAE induction. However, conflicting observations arose when EAE was induced in RAG1-deficient mice that underwent adoptive bone marrow transfer from LTα-deficient mice, thereby calling into question previous conclusions about the role of LTα in EAE development.

This study aimed to investigate the role of LTα in MOG35-55-induced EAE using mice deficient in LTα or its membrane receptor, LTβR. LTα knockout mice used here were designed to avoid the artifact involving TNF gene downregulation in myeloid cells, which occurred in the conventional LTα knockout mice.

Surprisingly, LTα-deficient mice with normal TNF expression developed EAE clinically comparable to wild-type mice. Conversely, genetic inactivation of LTβR delayed EAE onset. However, during the later stages of the disease, LTβR deletion exacerbated clinical symptoms of EAE.

These findings demonstrate that the involvement of LTα in EAE development is more complex than previously estimated, and that LTβR exhibits diverse functions depending on the disease stage: pathogenic at the early stage and protective at the later stages of EAE.

Russian Journal of Immunology. 2023;26(4):437-442
pages 437-442 views
Interaction between MSCS and blood mononuclear cells during in vitro co-cultivation in the presence of a three-dimensional artificial matrix mimicking regenerating bone tissue
Yurova K.A., Norkin I.K., Khaziakhmatova O.G., Malashchenko V.V., Melashchenko O.B., Ivanov P.A., Ligatyuk D.D., Khlusov I.A., Litvinova L.S.

Bone tissue repair and regeneration is a complex process involving many cells and controlled by multiple factors. Immune cells and cytokines play a crucial role in regulating the balance of bone formation and resorption. However, the immunomodulatory mechanism of bone regeneration is still unclear. Nevertheless, the reciprocal regulatory influence of immunocompetent cells and mesenchymal stem cells (MSCs) is well known. MSCs and immunocompetent cells secrete various cytokines, growth factors, and extracellular matrix molecules that play important roles in regulating hematopoiesis, angiogenesis, immune and inflammatory responses. Several studies confirm that different molecules expressed by MSCs may induce lymphocyte proliferation. Therefore, the study of the mutual influence of MSCs and blood mononuclear cells during in vitro co-cultivation, even in the presence of an artificial matrix mimicking regenerating bone tissue, is relevant and expedient. In this experimental series, the studies were performed at the interface between living and non-living substrate phases thus mimicking the “regenerating bone / hematopoietic microenvironment” system. A series of separated in time experiments was performed on a plastic surface (2D culture model) and in the presence of three-dimensional artificial matrices mimicking regenerating bone tissue (3D culture model).

Russian Journal of Immunology. 2023;26(4):443-448
pages 443-448 views
In vitro production of myeloid-derived suppressor cells from peripheral blood monocytes
Timganova V.P., Shardina K.Y., Bochkova M.S., Usanina D.I., Zamorina S.A.

Myeloid-derived suppressor cells (MDSCs) are of interest as key regulators of the immune response for the development and improvement of cellular technologies in biomedicine. Enhancing the suppressive activity of these cells is important for developing therapies for autoimmune diseases and miscarriages, and their suppression may be useful in the treatment of cancer, since MDSCs are known to suppress antitumor immunity. However, there is a problem that prevents the active study of MDSCs, i.e., the difficulty in obtaining sufficient numbers of this cell population. Isolation of MDSCs in cancer patients poses an ethical challenge. Moreover, these MDSC may differ in subpopulation composition and suppressive activity due to individual factors. Researchers who generate human MDSC from bone marrow cells may also face similar problems. Therefore, finding a reliable and affordable source of these cells to facilitate the study of their functions is extremely important. Attempts to obtain human MDSCs in vitro have been ongoing for a long time. GM- CSF, IL-6, IL- 1β, IL-4, PGE2, LPS, M-CSF, IFNγ are described as factors that induce the ex vivo MDSC differentiation. However, despite multiple factors used, not all protocols are clearly reproducible, leading to generation of a sufficient number of cells in the target population. Previously, we had also developed a scheme for MDSC differentiation from CD11b+ cells derived from human peripheral blood, which made it possible to obtain a tangible but still insufficient percentage of cells to study functional activity.

To increase the number of MDSCs in cultures, we developed a protocol aimed for differentiation of these cells from peripheral blood monocytes (CD14+ cells) previously transformed into PCMO (programmed cells of monocytic origin). The monocytes isolated by immunomagnetic separation were cultured in a de-differentiating medium (complete culture medium supplemented with M-CSF, IL-3 and β-mercaptoethanol) for one week. Later on, the medium was replaced by the addition of GM-CSF, being cultured for three days, followed by addition of LPS and IL-1β in order to induce suppressive activity. We have found that culturing CD14+ cells on a two-week schedule with prior creation of dedifferentiation conditions resulted in a slightly decreased percentage of viable cells in culture. However, there was a trend towards an increased ratio of MDSCs in culture (from an average of 34 to 40%) and an increase in their suppressive activity (arginase and IDO expression). The percentage of Arg+ cells increased by average of 10%, and IDO+ cells, by 16%. Moreover, the percentage of mature M-MDSCs was significantly (several-fold) higher when compared with differentiation protocol using CD11b+ cells. Hence, this method of MDSCs production enables us to increase the number of cells belonging to the conditionally “mature” monocyte subpopulation of MDSCs, as well as the percentage of functional suppressor cells in the population. The described scheme may be used to improve the quality of studies aimed at modulating MDSC functions in order to develop new therapeutic approaches.

Russian Journal of Immunology. 2023;26(4):449-456
pages 449-456 views
In vitro immunomodulatory effect of siRNA complexes in the influenza infection
Pashkov E.A., Samoilikov R.V., Pryanikov G.A., Bykov A.S., Pashkov E.P., Poddubikov A.V., Svitich O.A., Zverev V.V.

About 1.2 billion cases of influenza infection with up to 5 million cases of severe disease and up to 650,000 deaths from influenza and its complications are registered annually worldwide. High rates of morbidity and mortality are attributed to immunomodulatory properties of some proteins produced by the influenza viruses. Among these proteins, NS-1 is the most studied. One of its main functions is to disrupt the functioning of interferon-mediated defense mechanisms of the body thus causing suppressed production of different components of humoral immunity, which leads to an insufficiency of the immune response. It is known that miRNAs directed to cellular genes, which are involved in the process of viral reproduction, showing a pronounced antiviral activity. At the same time, only few studies have been focused on evaluation of their immunotropic effects. Therefore, the aim of our study was to quantify the concentrations of IFNα, IFNγ, TNFα and IL-10 cytokines as a result of complex suppression of the cellular FLT4, Nup98 and Nup205 gene activity, whose expression products play an important role in the reproduction of the influenza virus.

We have shown that the use of siRNA complexes also leads to an increase in the IFNα, IFNγ, TNFα and IL-10 concentrations. IL-10 production is absent on the first day after infection, but begins to increase on the second and third days. Moreover, in some cases, there is an increase in IFNα and IFNγ concentration on the first day after infection followed by decrease in their concentrations by the third day. This finding indicates that, upon supplement of the siRNA complexes, the cytokine profile is normalized under the influence of IL-10.

Russian Journal of Immunology. 2023;26(4):457-462
pages 457-462 views
Therapeutic effect of a new immunotropic composition tested in the model of periodontitis in experimental animals
Khlystova K.A., Chumakov N.S., Sarkisyan N.G., Kataeva N.N., Drozdova L.I., Tuzankina I.A.

The article deals with usage of a novel immunotropic drug composition in experimental model of periodontitis. The composition contains silicoorganic glycerogel, exhibits broad spectrum of action upon the etiological pathogen. A good therapeutic effect was revealed by clinical, laboratory and histological criteria. Histology showed absence of osteoclasts, reduced lacunas, higher density and normalization of tissue structures, recovery of microcirculation, angiogenesis and formation of granulation tissues. However, the phosphorus-to-calcium ratio in the group supplied with peroral vitamin D treatment, was characterized by significant decrease in alkaline phosphatase and inorganic phosphorus thus confirming efficiency of complex topical effect of the given composition and vitamin D.

Russian Journal of Immunology. 2023;26(4):463-470
pages 463-470 views
sIgA-protease activity of microorganisms isolated from the prostate secretion
Pashinina O.A., Kartashova O.L., Pashkova T.M., Gritsenko V.A.

Our aim was to characterize the ability of bacteria from prostate secretions of different taxonomic affiliations to inactivate secretory IgA (sIgA). Materials and methods: We performed experiments with 122 isolates of eight types of microorganisms isolated from prostate secretions of the patients with chronic bacterial prostatitis (CBP) and healthy males. The bacterial spectrum of microbiota was studied by bacteriological techniques, the species identification of microorganisms was carried out by mass spectrometry. The sIgA-protease activity of microorganisms was determined by the enzyme immunoassay using the “IgA secretory – ELISA-BEST” kit. Results: A wide prevalence of sIgA-protease activity has been detected in the microorganisms of different types isolated from prostate secretions of patients with CBP and healthy males. E. faecalis was the most active producer of sIgA proteases. We revealed an intraspecific and interspecific variability of the levels of sIgA-protease activity among Staphylococci. The microorganisms isolated from CBP were shown to express a significantly more pronounced ability to inactivate sIgA compared to strains isolated from healthy men.

Russian Journal of Immunology. 2023;26(4):471-476
pages 471-476 views
Differences in the skin microbiota spectrum and parameters of local immunity in the areas of inflammation in skin diseases and healthy people
Sennikova S.V., Toptygina A.P., Voropaeva E.A.

Alteration of microbiota composition is a trigger, and, sometimes, an etiological factor in the development of chronic skin diseases, e.g., psoriasis or eczema. Recognition of microflora by keratinocytes and immune cells leads to the production of antimicrobial peptides, chemokines and growth factors, which contribute to the differentiation of T lymphocytes to autoaggressive effector cells of Th1, Th17 and Th22 types that implement autoimmune inflammation in the psoriatic plaque. The aim of our work was to study the differences in the skin microbiota spectrum and the parameters of local immunity in capillary blood taken near the focus of inflammation in patients with autoimmune (psoriasis) and allergic (eczema) diseases compared with the parameters of healthy people. 24 patients with psoriasis (group 1), 20 patients with eczema (group 2) and 20 healthy adults (group 3) were examined. Biological materials were taken, i.e., the smears taken with sterile dry swab to the Amies transport medium with activated carbon, and capillary blood was taken in 2 microvets, 200 µL each) from the foci of inflammation on affected skin from the hands of patients, or from the fingers of healthy people. Inoculations of diagnostic media, microscopy with Gram staining and microbial identification were performed in a microbiological analyzer. Immunophenotyping of 22 subsets of mononuclear cells was performed by four-color staining of capillary blood with erythrocyte lysis and evaluation of subsets by a flow cytometer. Cytokines in blood plasma were determined by multiplex method. The spectrum of hand skin microflora of the group 3 was more diverse in the species composition. In patients with psoriasis and eczema, the coccal flora dominated, with a shift towards pathobionts in the microbiota spectrum. Activation of T and B cells, production of pro-inflammatory cytokines, IL-23/IL-17/IL-22 axis cytokines and cytokines – markers of epithelial cell damage (IL-25 and IL-33), as well as anti-inflammatory factors insufficiency were detected. Differences in changing parameters of the local immune status in patients with autoimmune (psoriasis) and allergic (eczema) diseases were revealed, thus reflecting the distinct features of immunopathogenesis in these diseases.

Russian Journal of Immunology. 2023;26(4):477-474
pages 477-474 views
Role of NLRP3 in the immunopathogenesis of neurodegenerative eye diseases
Balatskaya N.V., Gavrilova T.V., Kinkulkina A.R., Avagyan A.S., Svitich O.A.

Neurodegenerative eye pathology is one of the leading causes of visual impairment and blindness worldwide. Primary open-angle glaucoma (POAG) belongs to the group of neurodegenerative ophthalmic diseases and is characterized by a permanent or periodic increase in intraocular pressure, followed by development of typical visual field defects, decreased visual acuity and optic nerve atrophy. Recent studies show that local inflammation, triggered by the innate immune system is the first line of defense against the pathogens and tissue destruction products, playing an important role in the POAG pathogenesis. The aim was to study the neurodegenerative ophthalmic disorder in a rabbit model, and to compare the data on distribution of alleles and genotypes of the polymorphic marker rs7525979 of NLRP3 gene in the patients with POAG. At the first stage, we studied the complex tissue samples of the retina/retinal pigment epithelium (TCS/RPE) isolated from the eyes of 14 experimental animals and 7 intact rabbits without eye damage. Neurodegenerative pathology of the eye in rabbits was carried out in the Experimental Center at the Helmholtz National Medical Research Center by a single subretinal injection of 0.01 ml of 0.9% sodium chloride solution. NLRP3 gene expression levels in TCS/RPE samples were evaluated by real-time polymerase chain reaction (PCR-RV). At the second stage, peripheral blood samples were examined in patients who were diagnosed with POAG of various stages, as well as without glaucoma. DNA was isolated from blood samples, which was subsequently analyzed for the polymorphic markers study using PCR-RT technique. According to the results of the study, we noted an increased expression of the NLRP3 gene in the TCS/RPE samples from experimental animals with simulated retinal degeneration. Moreover, an association of alleles and genotypes of the NLRP3 gene was revealed in patients with POAG. The data obtained may be indicative for involvement of NLRP3 inflammasome components in development of neurodegenerative retinal lesions in POAG.

Russian Journal of Immunology. 2023;26(4):485-490
pages 485-490 views
Coordination of the NF-κB signaling pathway and lymphocyte metabolism in children with autoimmune diseases
Kurbatova O.V., Radygina T.V., Kuptsova D.G., Petrichuk S.V., Movsisyan G.B., Potapov A.S., Murashkin N.N., Abdullaeva L.M., Fisenko A.P.

Metabolic aberrations underlie many chronic diseases, including autoimmune diseases (AUD). Immune metabolism is an area of immunological research that is actively developing and studying the processes of metabolic reprogramming in immune cells. The regulation of the nuclear factor kappa B (NF-κB) activity, which is involved in the coordination of innate and adaptive immunity, inflammatory reactions and other processes, is being actively studied. The studies on immune metabolism and regulation of NF-κB is a promising direction in searching for new therapeutic approaches in the AUD treatment. The aim of the present study was to evaluate the informative value of NF-κB and the activity of intracellular lymphocyte succinate dehydrogenase (SDH) and glycero-3-phosphate dehydrogenase (GPDH) determined in children with immune-dependent disorders. 350 children with autoimmune diseases were examined: 97 patients with IBD, 72 children with relapsing-remitting multiple sclerosis (MS), 83 pediatric patients with psoriasis vulgaris (PS), and 97 children with autoimmune hepatitis (AIH). The comparison group consisted of 100 conditionally healthy children. Activity of mitochondrial dehydrogenases, i.e., SDH and GPDH, was evaluated by immunocytochemical method. The levels of NF-κB translocation (per cent of cells with NF-κB translocation from cytoplasm to cell nucleus) was determined by flow cytometry, with visualization. Statistical evaluation and plotting were carried out using the Statistica 13.0 software. The highest activity of SDH and GPDH was detected in the population of cytotoxic T lymphocytes and T helper cells, and the lowest activity of the enzymes was registered in the population of B lymphocytes, both in children with AUD and in comparison group. In children with AUD, there was a significant decrease in SDH activity in T lymphocytes, cytotoxic T lymphocytes, B lymphocytes and NK cells against the comparison group (p < 0.01). In children with PS, AIH and IBD, a decrease in SDH activity was revealed in Treg and Th17 cells. The most pronounced decrease in GPDH was characteristic of patients with AH (in T cells, cytotoxic T lymphocytes, B cells, NK cells and Tregs against the comparison group). In children with PS, the activity of GPDH was reduced only in Tregs (p < 0.05). For children with multiple sclerosis, a decrease in GPDH was revealed in populations of T lymphocytes, B lymphocytes and activated T helpers (p < 0.01). In the group of patients with IBD, there were no significant differences in the activity of GPDG relative to the comparison group. A significant increase in the level of NF-κB translocation in T helpers was revealed in all children with AUD relative to the comparison group. In children with AIH and PS, a significant increase in the level of NF-κB translocation was revealed in Treg, Thact and Th17 cells, in children with MS it was found in Treg cells, in patients with IBD, it was registered in Thact against the comparison group (p < 0.05). An inverse correlation was found between the levels of NF-κB translocation in lymphocyte populations, and activity of mitochondrial dehydrogenases in the lymphocytes. The most significant dependencies are characteristic of NK cells and T cell populations, and these correlations are valid for all groups of AUD patientsh. In the course of in vitro experiments with a drug of metabolic action, a decreased number of cells with NF-κB translocation and an increased SDH activity was observed; the degree of SDH activation depended on the cell population type, the greatest changes were detectable in the population of T lymphocytes (by 61%), in B lymphocytes (by 30%), in NK cells (by 19%). The study of the metabolic activity of lymphocytes and the NF-κB signaling pathway allows us to assess the general mechanisms of immunopathological processes in children with autoimmune diseases of various etiologies. As based on the inverse correlation between the level of translocation of NF-κB and the activity of SDH in lymphocytes, one may consider the use of an available immunocytochemical method being an analogue for assessing activity of the NF-κB transcription factor. The studies of immune metabolic correction of immunocompetent cells are a promising direction in the AUD treatment.

Russian Journal of Immunology. 2023;26(4):491-500
pages 491-500 views
Mitochondrial dysfunction as a probable mechanism for triggering inflammatory joint diseases
Goncharov A.G., Tatarkina M.A., Lobanova V.V., Kozenkov I.I., Dzhigkaev A.K., Gunbin K.V.

The article concerns the contribution of mitochondrial dysfunction to the development of inflammatory joint diseases. Mitochondria are the main suppliers of adenosine triphosphate (ATP). Reactive oxygen species (ROS) are a by-product of this metabolic process. Mitochondria also have an effective antioxidant mechanism: there is a certain balance between the ROS formation and their inactivation. Accumulation with age of mutations (single nucleotide substitutions, e.g., transversions, transitions, and deletions) in mitochondrial DNA, may cause a disorder in selective destruction (utilization) of damaged and dysfunctional mitochondria (mitophagy) thus leading to imbalance between the ROS production and their neutralization. This process is triggered by both internal factors (ROS overproduction) and external factors, i.e., tissue damage / injury and infection. The failure of quality control mechanisms resulting from disruption of mitophagy leads to a significant increase in terminally damaged mitochondria, which become a threat to cell survival. High level of genetic mutations accumulating with age in mitochondrial genome causes an increased formation of ROS, which, in turn, are one of the leading activators of the cytosolic NLRP3 protein, the main component of inflammasome type of the same name. Increased inflammasome formation ultimately triggers caspase-1 dependent production of pro-inflammatory interleukins-1β (IL-1β) and 18 (IL-18). Inadequate removal of damaged mitochondria leads to hyperactivation of inflammatory signaling pathways and, subsequently, to chronic systemic inflammation and development of inflammatory diseases, including primary osteoarthritis (OA). To assess the level of mitochondrial dysfunction, we assessed the numbers of mitochondrial genome copies in post-mitotic muscle cells in 48 patients aged 45 to 95 years who were diagnosed with OA of the knee or hip joints. As a result of our study, we have discovered and confirmed some regularities of human mtDNA mutations corresponding to those in vertebrates, and, in particular, in mammals. Degenerate mutation spectra (without classification of mutations by mtDNA chains and the context of surrounding nucleotides) were constructed for mtDNA in general, and for each individual sample. It was demonstrated that, in one-third of muscle samples, the critical threshold of mtDNA heteroplasmy was exceeded, at which the aberrant biochemical phenotype, in terms of oxidative phosphorylation functioning, (OXPHOS) becomes dominant. Of note, the heteroplasmy rates are lower in older patients who have had significant physical activity during their lives (sports, moderate physical work, etc.). Moreover, the heteroplasmy showed an inverse correlation with high mtDNA copy number. The results obtained can be used to diagnose pathologies in elderly, and the process of healthy aging.

Russian Journal of Immunology. 2023;26(4):501-506
pages 501-506 views
Сytokines as non-hormonal regulators in the pathogenesis of endocrinopathies
Valikova O.V., Zdor V.V., Sarychev V.A., Tikhonov Y.N., Boroda A.V.

Cytokines regulate the activity of hypothalamus – pituitary – adrenal hormonal axis, also affecting thyroid gland and ovaries. However, their exact role in pathogenesis of endocrine diseases is still under study. Altered cytokine secretion in autoimmune thyroid diseases and polycystic ovary syndrome is well known. Meanwhile, the main immunological predictors of severe prognosis in endocrinopathies and biomarkers for administration of targeted immunotherapy have not yet been determined. Therefore, our objective was to study the relationships between the cytokines and hormones in pathogenesis of autoimmune and non-autoimmune endocrinopathies, i.e., autoimmune thyroiditis (AIT), Graves’ disease (GD), nodular and multinodular goiter, polycystic ovary syndrome (PCOS).

101 patients with GD and 105 patients with AIT, 110 patients with PCOS were examined; 51 patients with nodular and multinodular euthyroid goiter and 50 healthy individuals; their average age was 34.5±2.9 years old. The study was approved by the Interdisciplinary Ethics Committee of the Pacific State Medical University. Clinical examination included ultrasonography. ELISA technique was applied for determination of thyroid and sex hormones, TSH, autoantibodies to TPO, TSH receptor, cytokines in blood serum, in follicular fluid samples, cell culture media (primary cultures of cumulus cells). Genetic studies were carried out with PCR. Morphological verification was performed by inverted microscopy CKX41 (Olympus) with a phase contrast system, camera AxioCam5 (Carl Zeiss) with software Zen 2, Blue Edition.

IL-6 and TNFα in the blood serum of patients with PCOS were most significantly increased, Sharply decreased IFNγ/IL-10 ratio in blood serum and cumulus cell culture was found in PCOS when compared with controls. Significant changes in the content of thyroid hormones in GD and TSH in AIT have been proven to affect the hyperproduction of pro- and anti-inflammatory cytokines. Before treatrment, the direct or reverse corelations were found between the levels of cytokines and thyroid hormones in GD, and TSH in AIT. Subsequently, upon correction of hormonal disorders, these associations became weaker, or faded away. In patients with nodular and multinodular euthyroid goiter, only the IFNγ level was significantly increased, being twice as high as in the control group.

A significant imbalance in the ratio of Th1/Th2 marker cytokines and their hyperproduction in autoimmune thyroid diseases made it possible to characterize the cellular response system in autoimmune thyroid disorders as highly active and directly associated with thyroid dysfunction, performing its effector function under the impaired immunoregulation. The revealed changes in pro-inflammatory cytokines in polycystic ovary syndrome represent new immunological markers of fertility, which may be a promising target for pathogenetic immunotherapy.

Russian Journal of Immunology. 2023;26(4):507-514
pages 507-514 views
Expression of IL-7 receptor on Th1, Th17 lymphocytes in patients with psoriatic arthritis
Blinova E.A., Angelskaya O.A., Kozlov V.A.

Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease of the joints, spine, and entheses that can occur in patients with psoriasis. The prevalence of psoriatic arthritis is high in Russia, in recent years there has been an increase in its incidence rates. The pathogenesis of PsA is based on the activation of Th1, Th17 cells. Pro-inflammatory cytokines produced by the cells are involved in the cascade of reactions leading to the joint deformity and bone destruction. For some autoimmune diseases associated with the Th1/Th17 response, IL-7 has been found to be involved in pathogenetic mechanisms. At the same time, IL-7 is assumed to support autoreactive T lymphocytes. Effect of the cytokine on cells is provided by the binding to a specific receptor thus causing a signal transmission into the cell and inducing the processes of differentiation, proliferation, and production of cytokines. In animal models of autoimmune diseases, usage of blocking antibodies to α-chain of the IL-7 receptor (IL-7R) was shown to cause reduced inflammation in target tissues and decreased number of infiltrating T lymphocytes. Therefore, the aim of this work was to investigate the in vitro effects of IL-7 and blockade of the α-chain of the IL-7 receptor on the contents of Th1, Th17 lymphocytes and expression of IL-7 receptor subunits on these cells in normal subjects and in psoriatic arthritis. The study included nine patients with PsA in the stage of exacerbation of the underlying disease (mean age 44±6.5 years) and 6 healthy individuals (mean age 45±2.7 years). The in vitro effects of IL-7 and specific blocking monoclonal antibodies (aCD127) was evaluated in cultures of mononuclear cells from peripheral blood. Flow cytometry was used to determine the expression of IL-7 receptor subunits (CD127, CD132) and to assess cell phenotypes in peripheral blood and cultured cells. We have shown for the first time that patients with PsA have an increased number of CD127+CD132- and CD127+CD132+ cells among Th17 lymphocytes, as well as CD127+CD132-, CD127+CD132+ and CD127-CD132+ cells among Th1 lymphocytes, which suggests participation of IL-7 in maintaining these cell populations. Upon the in vitro supplement of IL-7, an increase in the Th1 cell contents and a decreased number of Th17 cells were observed, both in donors and PsA patients, and the opposite effect was observed under the conditions of IL-7R of blockade. Under the influence of IL-7, as well as with blocking antibodies, there was a significant decrease in CD127 expression on Th1, Th17 lymphocytes. However, a decrease in the number of CD127-132+ among Th1, Th17 lymphocytes occurred only following blockade with antibodies. That is, despite redistribution of Th1 and Th17 lymphocytes in culture, the cells of these populations were not activated under the IL-7 receptor blockade. The obtained data may serve as a basis for choosing the IL-7 receptor as a target in the development of targeted drugs for the treatment of PsA.

Russian Journal of Immunology. 2023;26(4):515-520
pages 515-520 views
Single nucleotide polymorphism of osteoprotegerin as a possible biomarker of rheumatoid arthritis in Bashkir population of Chelyabinsk region
Chumacheva Y.V., Stashkevich D.S., Devald I.V., Suslova T.A.

Rheumatoid arthritis (RA) is a multifactorial autoimmune rheumatic disease of unknown etiology characterized by chronic erosive arthritis. The protein osteoprotegerin (OPG) is a member of bone tissue homeostasis (RANK/RANKL/OPG) which is responsible for the regulation of osteoclast differentiation and osteolysis. The altered binding of RANKL and OPG is one of the causes of many diseases with increased production of pro-inflammatory cytokines, including rheumatoid arthritis. Polymorphic variants of the genes that control protective reactions could affect the level of production for encoded proteins and, thus, changing the course of immune response in RA. G1181C SNP in osteoprotegerin gene leads to disruption of its transcriptional activity and conformation of the protein itself, which can lead to an imbalance of pro- and anti-inflammatory cytokines. We analyzed the relationship between the TNFRSF11B gene polymorphism at the 1181 G > C position and the risk of developing RA in the Bashkir population. The analysis was based on a molecular genetic study of single nucleotide polymorphism in groups of patients with rheumatoid arthritis and conditionally healthy individuals of the Bashkir population of the Chelyabinsk Region. Statistical evaluation was carried out using standard criteria generally accepted in immunogenetics. The 1181*GC polymorphism of the osteoprotegerin gene is characterized by interpopulation differences, which confirms the importance of using an ethnically identical comparison group to assess the association with a predisposition to multifactorial pathology. We showed that the carriage of genotype 1181 G/C was increased in the group of Bashkirs with rheumatoid arthritis. This genotype could be considered a biomarker of susceptibility to RA. No differences in the SNP allelic frequencies and genotypes were found among women with RA. Our research is a part of comprehensive assessment of the interaction of cytokines and their receptors from the TNFα superfamily as an immunogenetic component of RA genesis.

Russian Journal of Immunology. 2023;26(4):521-526
pages 521-526 views
Expression of “non-classical” molecules of the main histocompatibility complex in rheumatoid arthritis and bronchial asthma
Boeva O.S., Borisevich V.I., Kozlov V.A., Vladimirovna D.V., Sizikov A.E., Pashkina E.A.

HLA-E is a minor understudied non-classical HLA genes. HLA-E transcription is revealed in many cell types, especially, in immune cells, e.g., T and B cells monocytes, macrophages. In this work, we evaluated expression of HLA-E on CD8+, CD4+ and CD14+ cells in conditionallу healthy donors and in the patients with bronchial asthma (BA) and rheumatoid arthritis (RA). Peripheral blood mononuclears (PBMNC) were used as initial biomaterial. PBMNC from RA patients (n = 15), BA (n = 11) and healthy donors were separated from peripheral blood in Ficoll-Urographin density gradient (1.077 g/mL). The cells were then stained with fluorochrome-conjugated monoclonal antibodies: anti-CD3-APC, anti-CD4-APC-Cy7, anti-CD-14-FITC, and anti-HLA-E-PerCP/Cy5. The cell phenotype was analyzed by flow cytometry with FACS Canto II (BD Biosciences, USA). We have found an increased expression of HLA-E on CD8+, CD4+Т cells, like as on CD14+ cells (monocytes) in the RA patients, when compared with BA patients. We have also shown significant differences of HLA-E expression on CD8+Т cells between the conditionally healthy donors and RA patients.

Russian Journal of Immunology. 2023;26(4):527-532
pages 527-532 views
Characteristic changes of extracellular Dna levels, indices of netosis and inflammation in peripheral blood in patients with asthma
Gavrilova E.D., Goiman E.V., Demchenko E.N., Demina D.V., Volskiy N.N., Kozlov V.A.

Many studies have shown that the level of cell-free DNA (cfDNA) in blood of patients with oncological diseases, sepsis, systemic lupus erythematosus, and some rheumatic diseases significantly exceeds the value of similar index in healthy donors and is closely related to the clinical features of the disease. Systemic inflammatory response is among the most frequent pathophysiological processes along with markedly changed levels of cfDNA in blood plasma. The levels of cfDNA in blood plasma of patients with RA are shown to be closely associated with a shifted balance of helpers to the Th1-side. It is an adequate intensity index of inflammatory processes and effectiveness of therapy. At the same time, there only limited number of works concerning changes in cfDNA levels in pathological processes with predominance of Th2 lymphocytes. According to generally accepted concept, the pathogenesis of bronchial asthma is of distinct interest, being critically dependent on the production of specific antibodies controlled by activated Th2 lymphocytes. The aim of this work was to study the level of cfDNA in blood and compare its changes with intensity of NETs and inflammation in patients with asthma. The study included 20 patients with asthma, who underwent hospital treatment at the Department Allergology (Clinic of Immunopathology, RIFCI, Novosibirsk), and 10 conditionally healthy donors. We have shown that, upon admission to the clinic, the level of cfDNA in patients with asthma was significantly reduced against the control group of healthy donors. After a course of therapy, the average level of cfDNA in patients’ plasma was increased and did not differ statistically significantly from this index in controls. The data obtained for other parameters indicate that the patients with asthma did not reveal any signs of pronounced systemic inflammatory response. One should suggest that the observed changes in the level of cfDNA in blood plasma in bronchial asthma are not caused by chronic inflammatory process in lungs of these patients, but they are determined by some other pathophysiological mechanisms. It has been shown that the level of in vitro stimulated NETs in patients with asthma is higher than in healthy donors, thus being consistent with current opinions on the role of neutrophils in pathogenesis of asthma.

Russian Journal of Immunology. 2023;26(4):533-540
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Concomitant infections in children with allergic pathology in the Kaliningrad region
Markhaychuk A.Z., Pleshkova A.O., Mun A.C., Goncharov A.G.

The aim of our work was to study the structure and prevalence of the infectious syndrome in children from Kaliningrad Region with moderate-to-severe allergic pathology, with a complex manifestations of allergic reactions, both on skin and on the mucous membranes of the digestive and respiratory tract.

Ninety children from 0 to 18 years old with various symptoms of allergic pathology were examined and included in the study group using standard clinical, objective and laboratory criteria. The severity of clinical course was associated with the severe and long-lasting symptoms, as well as with frequent bacterial and bacterial-fungal complications, with impaired quality of life and night sleep. The children were consulted by the specialists in otorhinolaryngology, hematology, pulmonology, surgery, ophthalmology, infectology, endocrinology, cardiology. Diagnoses according to nosological forms were made in accordance with the current clinical recommendations of Russian Ministry of Health. Our article presents data on concomitant infectious diseases and their impact on general condition and severity of hypersensitive responses. The average age of allergic manifestations in the group of children was 3.12±2.72 years. The average duration of the disease in the observed group was 7.5±0.88 years. The number of boys in our group prevailed (n = 56) by 1.6 times. Complicated heredity factors were reported by < 15% of the patients’ parents. However, with careful collection of medical history taking, upon dynamic observation, the aggravated heredity on the mother’s side was detected in 45.56% (n = 41), and on the father’s side, in 31.1% of cases (n = 28). In eight families, both parents suffered from allergic pathology, in siblings, 21.1% (n = 19) of the examined children had allergies. In the families, including grandparents, allergic pathology was reported in 56 cases (62.2%).

Almost all patients had problems with nasal breathing, 77 (85.6%) children with adenoid hypertrophy had a habit of breathing through the mouth. Postnasal drip syndrome was found in 78 cases. Allergic rhinitis with adenoid hypertrophy is, generally, accompanied by postnasal leakage, which can provoke aspiration bronchitis and pneumonia, especially if pathogenic or opportunistic flora is transferred to the nasal cavity and/or to the pharynx.

Conclusions: 1. Identification and rehabilitation of chronic foci of infection, bacterial, fungal, should be a necessary component of the personalized therapy of allergic pathology in children. 2. In cases of recurrent sowing or finding of pathogenic flora (iodophilic flora, fungi, coccal flora) in the coprogram, one should exclude not only transient lactase deficiency, but also congenital lactase deficiency, thus preventing development of enterocolitis in the future like as worsening of skin status and respiratory manifestations. 3. In case of severe respiratory viral infections in children during the period of adaptation for pre-school institutions, one should exclude sensitization to allergens of house dust mites and epidermal allergens of domestic animals. 4. A comprehensive and personalized approach to the diagnosis of allergic disorders and comorbid conditions enables us to create conditions for stable remission, making it possible to conduct allergen-specific immunotherapy, which may provide a disease-modifying effect upon the hyperreactive states in our patients.

Russian Journal of Immunology. 2023;26(4):541-546
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Markers of eosinophilic inflammation of airways in patients with fungal sensitilization
Vasiliev N.Y., Kozlova Y.I., Frolova E.V., Uchevatkina A.E., Filippova L.V., Aak O.V., Sobolev A.V., Vasilieva N.V.

Immunological characteristics of airway inflammation in asthma patients with sensitization to various fungal allergens are not well understood, and the search for new markers is necessary to establish future targets for targeted therapy. The purpose of our study was to assess the levels of eosinophilic inflammation markers of the respiratory tract in patients with severe asthma and allergic bronchopulmonary aspergillosis, depending on the spectrum of fungal sensitization.

The study included 31 patients with severe asthma with fungal sensitization and 29 patients with allergic bronchopulmonary aspergillosis (ABPA). The levels of total, specific IgE to fungal allergens and periostin in blood serum were determined by enzyme immunoassay. The study of basophil activation was performed by flow cytometry.

The patients with severe asthma and sensitization to Aspergillus spp. and Alternaria spp. had significantly higher levels of eosinophils, periostin, and stimulation index to Alternaria spp. in the basophil activation test when compared with the group of asthma patients with sensitization to Aspergillus spp. only. In patients with ABPA with combined sensitization, we have found significantly higher levels of eosinophils, periostin, and stimulation index to Alternaria spp.

The finding of pronounced eosinophilic type of inflammation in patients with asthma and combined sensitization to thermotolerant and thermolabile fungi may result from aggressive effect of fungal allergens on the barrier functions of bronchial epithelium, which should be taken into account when choosing therapeutic strategy and administration of immunobiological therapy.

Russian Journal of Immunology. 2023;26(4):547-552
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Indices of cellular and humoral immunity in a patient with a history of central precocious puberty in anamnesis
Khisamutdinova D.R., Kozlova Y.I., Башнина E.B., Frolova E.V., Uchevatkina A.E., Filippova L.V., Vasilyeva N.V.

The etiology of precocious puberty includes organic anomalies, genetic mutations, but the primary cause remains unclear in the vast majority of cases. Gonadotropin-releasing hormone (GRH) agonists are used as a treatment of gonadotropin-dependent precocious puberty. Blocking the secretion of gonadotropin-releasing hormone, these drugs stop the premature development of sexual features, prevent premature closure of ossification zones, thereby increasing the child’s expected adult height. The interest in the effects of this group of drugs beyond the hypothalamic-pituitary-gonadal axis has been recently increased. A series of clinical cases have been reported on the development of autoimmune diseases, e.g., autoimmune thyroiditis, Graves disease and type 1 diabetes. The article presents a clinical observation of a patient with central form of premature development who exhibited satisfactory response to treatment with a GRH agonist drug. Further follow-up did not show any reproductive dysfunction. Upon immunological examination, a disturbance was revealed only in the cellular component of immunity. An increased metabolic activity of neutrophils was found, thus, probably, indicating a nonspecific inflammatory process. The levels of immunoglobulins A, M, G matched the reference values. Thus, the therapy with a drug from the group of GRH agonists was effective and safe in terms of influencing the patient’s immune system. The role of hormonal disorders and effects of GRH agonists on the development of immunopathological conditions require further research.

Russian Journal of Immunology. 2023;26(4):553-558
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A clinical case of secondary eosinophilia in a child
Mukhametzyanova V.G., Rybakova O.G., Palchenko P.M., Петрунина S.Y.

A couple of decades ago, the diagnostic search for the cause of blood eosinophilia concerned, mainly, the three major allergic diseases (bronchial asthma, allergic rhinitis, atopic dermatitis), or parasitic invasion. In recent years, more and more complex clinical syndromes, from reactive (secondary) eosinophilia to eosinophilic leukemia are increasingly considered by the doctors of different specialties. The aim of our work was to present a clinical case of secondary eosinophilia in a child with minimal clinical manifestations. Highlights: Sometimes blood eosinophilia in a patient is an “unexpected finding” for a physician, especially if the complaints are scanty, nonspecific, and objective examination does not reveal any significant health abnormalities. In the presented case, secondary (reactive) peripheral blood eosinophilia was diagnosed due to intestinal damage induced by food allergens. This clinical case is of practical interest to physicians, presenting a diagnostic search for the cause of blood eosinophilia, which eventually proved to be a mixed IgE/ non-IgE mediated food allergy manifesting as allergic enterocolitis. The IgE-mediated mechanism of food allergy is evidenced by a high level of IgE and its decrease with administered elimination diet; delayed-type response and low severity of clinical manifestations of food allergy, as well as blood eosinophilia suggest a non-IgE mediated food allergy. In this particular case, the severity of laboratory changes (blood eosinophilia, a significant increase in the levels of specific IgE) was associated with scarce intestinal symptoms. An opposite situation is observed, especially, in young children where the disease manifests with a pronounced clinical pattern of enterocolitis in the absence of laboratory changes.

Russian Journal of Immunology. 2023;26(4):559-566
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Contents of matrix metalloproteinase type 2 (MMP-2) and complexes MMP-9/TIMP-1, MMP-2/TIMP-2, and total cholesterol in practically healthy people and patients with hypertension
Chepurnova N.S., Knysh S.V., Yushchuk V.N., Markelova E.V., Sanatsky K.R., Yushchenko A.N., Yermolitskaya M.Z.

Arterial hypertension (AH) is the most common age-associated disease among the working population. Polyetiology of AH requires a more thorough definition and study of its predictors aiming for understanding the role of external influences, as well as detection of genetic polymorphisms at early stages, in order to limit their implementation. The scientific reviews discuss the important role of abnormal vascular remodeling in the pathogenesis of hypertension. The main factor of such alterations is the rearrangement of extracellular matrix due to matrix metalloproteinases (MMP), the zinc-dependent enzymes with a wide substrate specificity. In addition, in more than 70% of cases, AH is combined with lipid metabolism disorders, including an increase in cholesterol levels. These mechanisms should be taken into account when assessing risk factors for development of cardiovascular accidents. The role of MMP-2 and the complexes MMP- 9/ TIMP- 1, MMP-2/TIMP-2 in pathogenesis of vascular restructuring is insufficiently described in the review articles. The article presents our results of studying the system of proteolytic enzymes and the level of total cholesterol in 110 practically healthy people and 90 persons with AH aged 18 to 74 years old. The levels of MMP-2, MMP-9/ TIMP- 1, MMP-2/TIMP-2 complexes in blood serum were studied by the sandwich variant of ELISA technique. Statistical processing of the obtained data was carried out using the analytical software IBM SPSS Statistics, v. 22.0.1. It was found that in the groups of women, regardless of the presence, or absence of pathology, the level of total cholesterol is higher if compared with male subjects. MMP-2 values were low both in the general group of practically healthy people, regardless of gender, and in the group of men with hypertension. Proteolytic activity of MMP-2 shows a broader substrate activity in women with hypertension. In the group of practically healthy men and women, we have registered lower levels of the studied MMP complexes and their tissue inhibitors. An imbalance in the proteolysis/antiproteolysis system is observed both in the group of hypertensive women with more pronounced effects upon migration, proliferation and apoptosis of smooth muscle cells, endothelial and inflammatory cells, thus determining formation of intima and arterial remodeling, as well as in the group of men with hypertension with predominance of remodeling factors that affects the rigidity of vascular wall.

Russian Journal of Immunology. 2023;26(4):567-572
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Dynamics of the level of transforming growth factors in blood serum in acute kidney injury in patients after coronary artery bypass grafting
Markelova E.V., Fisenko V.G., Zenina A.A., Silaev A.A., Yermolitskaya M.Z., Shumatov V.B.

Acute kidney injury (AKI) is among most dangerous and common complications after oper-heart cardiosurgical operations. Therefore, a search is carried out for biological markers which could timely detect this condition. The article presents dynamics of TGF-β1, TGF-β2, TGF-β3 in blood serum prior and after a coronary artery bypass (CAB). The study included 120 patients with multivascular affection of coronary blood flow , and 50 conventionally healthy persons of similar age. The 1st group included 50 patients without evidence of AKI, the 2nd group consisted of 70 patients with AKI. Serum TGF-β1, TGF-β2, TGF-β3 was determined by ELISA technique in the main groups before (1) and after surgery (2) as well as on day 2 after operation (3), on day 7 after surgery (4), and once tested in the control group.. The results were expressed in ng/mL or pg/mL, as median values, upper and lower quartiles. Significance levels were determined by the Wilcoxon criterion. We have revealed dynamic changes of TGF-β levels in serum of the patients before and after CAB. Initially, before operation, we have found normal TGF-β1 levels and low TGF-β3 levels in the both main groups. Meanwhile, increased TGF-β2 levels are found only in the subgroup with subsequent AKI development. The dynamics of TGF-β1 showed a decrease just after surgery and 2 days later, being increased over initial level on day 7, and there were no significant differences for the groups with versus without complications. No dynamic differences were revealed for TGF-β2 in the patients of group 1 after surgery. Meanwhile, the group 2 after CAB displayed higher TGF-β2 values compared with controls during the entire follow-up period, neing, however, higher that in the group on the 2nd day following surgery. The TGF-β3 levels were increased just after surgery in both groups followed by subsequent decrease in group 1. In the 2nd group after CAB, the initial deficiency of TGF-β3 was changes in wave-like mode, over 2nd and 3rd period of monitoring. It was increased on day 7, becoming higher than in group1 but did not reach reference values. Further studies in the AKI group after CAB which depend on their severity and outcomes may detect new features of TGF-β system in the patients with this disorder.

Russian Journal of Immunology. 2023;26(4):573-578
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Immune system dysfunction in purulent inflammatory diseases of the maxillofacial area in pediatric patients
Mitropanova M.N., Ponomarenko T.A., Chudilova G.A., Teterin Y.V., Chapurina V.N.

The issues of treatment of purulent inflammatory diseases of the maxillofacial region (PMMA) are quite urgent, due to increasing number of such patients. Their clinical course is getting worse, and the efficiency of antibiotic therapy is decreasing. Clinical outcomes of purulent maxillofacial pathology in children are complicated by potential severe local deformities at the growth areas of the jaw bones which are difficult to eliminate. The number of cases of prolonged and chronic inflammatory processes, development of local and general complications is increased. The reason for these complications may be an impaired susceptibility to infectious agents, which is determined by the state of the immune system. Therefore, our aim was to reveal some features of immune functions in children with purulent-inflammatory diseases of maxillofacial area.

The study included a group of pediatric patients 8-17 years old with maxillofacial inflammatory diseases of the maxilla (the study group), and 13 conditionally healthy children (the comparison group). The contents of T cells (CD3+CD19-, CD3+CD4+, CD3+CD8+, CD3+CD4+/CD3+CD8+), and В cells (CD3-CD19+), NK (CD3-CD16+CD56+) was determined using Cytomics FC-500 (Beckman Coulter, USA);concentrations of serum IgA, IgM, IgG were determined by ELISA technique (Vector-Best, Russia). Phagocytic activity of neutrophilic granulocytes (NG) was evaluated as percentage of actively phagocytic NGs, capturing processes were assessed by appropriate phagocytic indices, and the digestive activity was evaluated against S. aureus (strain 209).

Combined defects of immune response in children with maxillofacial hypertension were established: decrease of T lymphocytes contents along with decrease of T helpers and CTL ratio along with unchanged content of NK cells and B lymphocytes. Increase of IgA and IgG levels was also found. Defects of phagocytosis were revealed, primarily connected with the processes of completed phagocytosis and increased content of actively phagocytizing NG.

Treatment of children suffering with purulent inflammatory diseases of maxillofacial region is still an urgent problem in dentistry. The revealed dysfunction of immune response to pathogens in the purulent maxillofacial disorders may explain a prolonged clinical course of inflammatory processes, thus determining a need for usage of immunotropic therapy in complex treatment schedules including operative aid as well as conventional drug and physiotherapeutic treatment aiming for increase of rehabilitation efficiency and prevention of postoperative complications in these patients.

Russian Journal of Immunology. 2023;26(4):579-586
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Analysis of regulatory T lymphocytes in patients with traumatic brain injury
Norka A.O., Vorobyev S.V., Kuznetsova R.N., Serebriakova M.K., Kudryavtsev I.V., Kovalenko S.N., Monashenko D.N.

In recent years, traumatic brain injury (TBI) has been one of the most urgent medical and social problems due to its prevalence, predominantly affecting young people of working age, causing high mortality, disability and economic costs for treatment and subsequent rehabilitation of patients. At present, the role of patients’ immune system in evolving neuroinflammation after traumatic brain injury has been proven. Treg cell populations represent an important factor determining the outcome of the disease due to promoting induction of immunological tolerance, being a significant component of immunoregulation. As a result of our study, we found a decrease in the relative content of Treg within the total lymphocyte pool of peripheral blood, which has the CD3+CD4+CD25bright phenotype in patients of the 3rd and 4th groups, in comparison with the data from control group. Moreover, a decreased relative content of Tregs (CD4+CD25+T cells) was revealed which is due to the degree of brain tissue damage and, as a result, their migration to suppress inflammation due to production of anti-inflammatory cytokines (TGF-â, IL-10). The Treg population is heterogeneous, thus prompting us for analysis of the Treg subpopulations profile based on the expression of CD45R0 and CD62L. When assessing subpopulations of regulatory T lymphocytes within CD45Ro and CD62L, significant changes were found only in patients with brain contusion. The changes were revealed within the pool of “naive” T regulatory lymphocytes with the CD3+CD4+CD25brightCD39+ Treg phenotype, capable of producing a wide range of cytokines specific for Th1, Th2, Th17, in patients with mild, moderate and severe TBI. Meanwhile, the level of highly active CD3+CD4+CD25brightCD73+ Tregs was significantly reduced in patients with moderate and severe TBI. These changes indicate an imbalance in immunoregulatory processes resulting from extensive damage to brain tissues.

Russian Journal of Immunology. 2023;26(4):587-592
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Leukocyte cytokine expression is associated with severity of autism in children
Filippova Y.Y., Alekseeva A.S., Burmistrova A.L.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with unknown etiology, high clinical heterogeneity and marked aberrations of the immune system. Evidence for an association between immune dysfunction and behavioral traits highlights the need for a study of the immune cell functional activity in order to search for pathogenesis mechanisms and potential targets for therapy at ASD. The purpose: to determine the expression levels of IL-1β, IL-2, IL-4, IL-6, IL-10, IL-18, IFNγ and TNFα in peripheral blood leukocytes of children with mild and severe ASD. The study included 81 children with ASD (77.8% boys) and 45 children with typical neurodevelopment (TDC, 71.1% boys). According to the Childhood Autism Rating Scale, 51 children (63.0%) had mild autistic symptoms (CARS score 32.0±1,5) and 30 children had severe ASD symptoms (CARS score 39.0±3,4). Cytokines expression in leukocytes was determined by quantitative PCR with SYBRGreen. The data were transformed using Box–Cox transformation. The differences between groups were assessed by one-way ANOVA and Dunn’s test for multiple comparisons. In leukocytes of children with ASD, regardless of the severity, the expression of IL-1β, IL-18 and IL-2, was significantly reduced compared to TDC. Moreover, in children with mild ASD, low expression of TNFα, compared with TDC was found. In children with severe ASD, the expression of the main cytokine of Th1 – IFNγ, was significantly increased, without an increased expression of an important cytokine of Treg – IL-10. Activation of the Th1 adaptive immune response without compensation by cytokines of Treg, the number of which is reduced in ASD, can lead to increased inflammation, even in the central nervous system, and correlates with the severity of ASD clinical symptoms. Despite extensive immunological evidence suggesting immune system dysregulation, further research is required to clarify the relationship between immune system cell function and ASD pathology.

Russian Journal of Immunology. 2023;26(4):593-598
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Immunological and biochemical markers of adverse outcome in COVID-19 and arterial hypertension
Mordyk A.V., Bagisheva N.V., Moiseeva M.V., Antipova E.P., Streltsova V.V.

Coronavirus is able to affect various organs and systems including the immune system. At the same time, the state of the immune system may be initially changed in patients with pre-existing comorbid non-infectious disorders. The aim of our study was to evaluate biochemical and immunological markers of adverse outcomes in the patients with new coronavirus infection with underlying arterial hypertension.

The retrospective study included 47 patients with COVID-19 and arterial hypertension, who underwent a study of C-reactive protein (CRP), interleukin-6 (IL-6), assessing the increased values of these markers and the outcomes of the disease. The study group included 23 male and 24 female patients at the median age of 54 (for men), and 57 years old (for women).

Upon admittance of the patients with COVID-19 and hypertension to the hospital, a parallel increase in both CRP and IL-6 was registered in these cases. Statistically significant differences were found in the levels of CRP and IL-6 in patients with a favorable versus unfavorable clinical outcomes. The levels of CRP and IL-6 in deceased patients were higher and did not tend to decrease. Thus, the simultaneous increase in CRP and IL-6 in patients with COVID-19 and hypertension is considered an unfavorable prognostic parameter for patients’ survival.

Russian Journal of Immunology. 2023;26(4):599-602
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Сytokine expression and production in severe cases of SARS-CoV-2 infection
Abramova N.D., Meremyanina E.A., Kalyuzhnaya N.O., Poddubikov A.V., Kostinov M.P., Grechenko V.V., Svitich O.A.

Most respiratory viral infections proceed in mild form including COVID-19. Gowever, some patients experience severe systemic inflammation, tissue damage, acute respiratory distress syndrome, and cytokine storm with potentially lethal outcomes. The cytokines have been thought to play an important role in immunopathology of viral infection. However, an excessive immune response, manifesting as massive release of pro-inflammatory cytokines, may cause immune damage in the body. Production and release of the cytokines in healthy individuals presumes a significant balance of inflammatory and homeostatic factors. Meanwhile, in the case of COVID-19 disease, uncontrolled increased production of cytokines often occurs with fatal consequences for patients. The aim of this work was to study the level of IL-1β, IL-18 and TNFα gene expression, as well as production of these cytokines at the level of mucous membranes of the upper respiratory tract, in particular in oral cavity, in patients with severe COVID-19 disease.

The present study included patients who recovered from severe COVID-19. The control group consisted of conditionally healthy individuals. Expression levels of the IL-1β, IL-18, and TNFα genes were determined by RT-PCR. The levels of IL-1β, IL-18 and TNFα protein production were determined by multiplex enzyme immunoassay.

The expression levels of IL-1β, IL-18 were reduced at the onset of the disease, as well as in the midpoint of the COVID-19 disease, but increased on the 30th day. The protein production of these cytokines was also reduced in the first days from the onset of the disease. The levels of pro-inflammatory TNFα cytokine was high at the onset of the disease. The level of TNFα production at the onset of the disease was also higher relative to the control group. Subsequently, the TNFα gene expression levels decreased upon progression of the disease.

Thus, the increased expression level of pro-inflammatory cytokines may be explained by the fact that the S protein of the SARS-CoV-2 virus induces increased expression of these cytokines in human monocytes. Meanwhile, appropriate protein levels remain low, especially on day 1 from the onset of the disease. Thus, one may conclude that the virus triggers pyropotosis, however, within 15-30 days from the onset of the disease, when viral replication is already minimal.

Russian Journal of Immunology. 2023;26(4):603-610
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Levels of TREC and KREC molecules significance determining in peripheral blood for predicting the outcome of COVID-19 disease in the acute period
Saitgalina M.A., Ostankova Y.V., Arsentieva N.A., Korobova Z.R., Liubimova N.E., Kashchenko V.A., Kulikov A.N., Pevtsov D.E., Stanevich O.V., Chernykh E.I., Totolian A.A.

The disease caused by the highly contagious SARS-CoV-2 virus – “novel coronavirus infection (COVID-19)” – had killed more than 6.5 million people at the end of December 2022. The severity of the manifestation of the infectious process varies from asymptomatic forms to rapid progression to life-threatening conditions requiring emergency measures. One of the factors, the severity of which affects the outcome of the disease, is lymphopenia, the cause of which may be a violation of lymphopoiesis. The identification of laboratory markers of a high risk of mortality in patients with COVID-19 plays an important role in improving patient care algorithms and increasing their survival. Levels of TREC and KREC molecules in peripheral blood, respectively, can serve as molecular markers of the severity of T and B lymphopenias. The aim of our work was a comparative analysis of the levels of TREC and KREC molecules in the peripheral blood of surviving and deceased patients with COVID-19. The material was whole blood samples obtained from 1745 people, including: 1028 patients diagnosed with novel coronavirus infection (COVID-19) (ICD-10 code – U07.1), of which 937 patients recovered and 91 died; 717 apparently healthy individuals (control group). The levels of TREC and KREC molecules were assessed by quantitative multiplex Real-time PCR using the TREC/KREC-AMP PS reagent kit (Federal Scientific Research Institute Pasteur, St. Petersburg). Statistically significant differences in the levels of KREC and TREC molecules between the control group and patients, both surviving and deceased, were established. A significant decrease in median concentrations of KREC molecules was shown in patients with a lethal outcome compared with survivors (p = 0.0019, 95% CI). Among the deceased patients, in 63.7% of cases, the levels of TREC or KREC molecules were reduced relative to the corresponding age norms. Of these, in 20.9% of cases, both analytes were reduced in patients. When assessing the diagnostic significance of the levels of the analytes under study for predicting the outcome of the disease, the area under the AUC curve for KREC was 0.63±0.029, which indicates the average strength of the prognostic model of the patient's death depending on the level of KREC in the blood. The constructed model is statistically significant (p = 0.002). Monitoring laboratory parameters of patients with COVID-19, including those who died, allows you to determine the prognostic factors that are most significant for assessing the outcome of the disease. Based on the assessment of the KREC level, a predictive model with high specificity reflects the risk of death in patients with COVID-19. Thus, the quantitative determination of the level of KREC molecules in the peripheral blood can be attributed to the methods of preventive personalized diagnostics aimed at improving the survival of patients.

Russian Journal of Immunology. 2023;26(4):611-618
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Features of immune status in patients with acute coronary syndrome with and without COVID-19, depending on the level of B1 lymphocytes
Safronova E.A., Ryabova L.V., Zurochka A.V.

The aim of our study was to evaluate the blood cell indices and phagocytic activity of neutrophils in persons with acute coronary syndrome, depending on their history of COVID-19 infection.

The study involved 65 males aged 35 to 65 years with acute coronary syndrome (acute myocardial infarction and unstable angina pectoris). All patients underwent coronary angiography and stenting of the coronary arteries within 3 days from the terms of admission to the hospital. The following clinical examination were carried out: a general blood test by a standardized method on a hematological analyzer Medonic M20 (Sweden). Of immunological indices, the phagocytic activity of neutrophils was assessed. Spontaneous and induced NBT test of neutrophils was determined by light microscopy using light microscopy (Olimpus, Japan). The phagocytic activity of neutrophils was recorded by their ability to absorb latex particles. B1 lymphocytes were determined using flow cytometry.

All patients, depending on the content of B1 lymphocytes and the presence or absence of COVID-19 in previous history, were divided into 6 groups: patients with COVID-19 and those with reduced (group 1), normal (group 2), or elevated number of B1 lymphocytes (group 3). The patients who did not have COVID-19 were also classified into those with low (group 4), normal (group 5), or elevated B1 lymphocytes (group 6). The numbers of leukocytes in routine blood test were significantly higher, and the average corpuscular volume of hemoglobin was lower in the patients who have undergone COVID-19. Platelet counts were higher in post-COVID-19 patients, being maximal at normal B1 lymphocytes. The largest number of monocytes was recorded in patients with COVID-19 and normal B1 lymphocytes, and the minimal content of monocytes was registered in patients of group 4. The highest number of granulocytes was observed in individuals who did not have COVID-19, with reduced B1 lymphocytes. Thrombocytocrit was the highest in group 2 patients. The activity and intensity of neutrophil phagocytosis was lower in individuals with a history of COVID-19 and elevated B1 lymphocytes. The phagocytic number of neutrophils was minimal in those patients without COVID-19 who had low B1 lymphocytes. The maximal spontaneous HBT activity was recorded in individuals with high B1 lymphocytes and a history of COVID-19, and the minimal values have been recorded in those with low B1 lymphocytes and previous COVID-19. NBT spontaneous index was also the highest in patients of the 3rd group. The minimal NBT-induced activity and index were noted in group 1. The most severe patients were in groups 1 and 2. In group 1, 50% were diagnosed with acute myocardial infarction, stent thrombosis was diagnosed in 2 patients, four patients deceased. Among patients with normal B1 cell contents and a history of COVID-19, 2 patients died, 2 patients had stent thrombosis, 65% had acute myocardial infarction. These groups had higher platelet levels and lower HBT activity, both spontaneous and induced.

In patients with acute coronary syndrome and prior COVID-19, in comparison with persons without a history of COVID-19, there is an increased number of leukocytes, platelets, a decrease in the activity and intensity of neutrophil phagocytosis, spontaneous and stimulated NBT activity, which was most pronounced in patients with low B1 lymphocytes. The most clinically severe patients were found in the group of people who had undergone COVID-19 and had low B1 lymphocytes.

Russian Journal of Immunology. 2023;26(4):619-626
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Time-dependent changes of platelet and D-dimer parameters in vaccinated versus non-immunized COVID-19 patients
Kostinov M.P., Zhang C., Khrapunova I.A., Pechenik A.S., Utkin V.A., Loktionova M.N., Mashilov K.V., Soloveva I.L.

There are increasing data concerning changes in hematological (clinical) and biochemical blood tests in patients with COVID-19 infection, which indicate the severity of the manifestations of the infectious process. Coagulopathy often correlates with the severity of COVID-19 disease and the risk of death. In this regard, prediction of developing coagulopathy and its prevention remain quite relevant. The aim of our study was to identify differences in the content of platelets and D-dimer in patients with COVID-19. The study included cohorts of patients vaccinated against SARS-CoV-2, and those not immunized against this infection.

A prospective, randomized, observational study of the patients’ response was performed in cohorts of 588/52.2% vaccinated (vaccinated) and 588/52.2% non-immunized (non-vaccinated) patients with diagnosed COVID-19 over the period from 23.06.2021 to 01.05.2022. The levels of blood platelets and D-dimer, as well as clinical outcomes of the disease in patients with COVID-19, were studied in dynamics on days 1-2, 5-6 and 10-12 of hospitalization.

Upon admission, the normal value of the blood platelet counts did not differ between the compared groups, being 206.58 × 109 in vaccinated group and 204.85 × 109 in the unvaccinated group, respectively. a moderate increase in the concentration of D-dimer was noted in both groups upon admission, i.e., 2838.60 ng/mL in the group of vaccinated patients and 3242.08 ng/mL among the unvaccinated patients. In the course of the study, we have shown that the dynamics of D-dimer index in vaccinated versus non-immunized persons was similar according to the days of disease, showing an increase from the first day and a trend towards an higher values, starting from 5-6 days. At the same time, the dynamics in the vaccinated patients was somewhat less favorable than that of the non-immunized subjects. In the patients who were not immunized throughout the entire observation period, the platelet count exceeds the levels found in vaccinated subjects, thus suggesting higher risk of thrombosis and cytokine storm.

The data obtained show that the dynamics of D-dimer and platelet counts in vaccinated and non-immunized people is similar on appropriate terms of the illness. However, the changes are more pronounced in vaccinated cohort, but it does not indicate a greater risk of adverse outcomes.

Russian Journal of Immunology. 2023;26(4):627-632
pages 627-632 views
Mucosal humoral immune response of respiratory tract in medical workers during the post-COVID-19 period
Kryukova N.O., Khasanova A.А., Baranova I.A., Kostinov M.P., Svitich O.A., Chuchalin A.G.

Currently, the role of local respiratory tract immunoglobulins in COVID-19 and rearrangement of mucosal immune response in the post-COVID period have not been sufficiently studied. Our aim was to evaluate long-term effects of novel coronavirus infection on the mucosal immunity in healthcare workers over the post-infection period.

A total of 180 healthcare workers, ranging in age from 18 to 65 years, were enrolled in a one-stage, cross-sectional study. The subjects with a history of COVID-19 were divided into three groups, depending on the severity of their disease. The control group consisted of 44 healthcare workers who had no history of novel coronavirus infection. Secretory immunoglobulin A (sIgA) and total immunoglobulin G (IgG) levels were quantified in saliva samples, induced sputum samples, naso- and oropharyngeal scrapings by ELISA technique. Specific anti-SARS-CoV-2 IgG antibodies were quantified in the serum by chemiluminescence immunoassay.

Numerous shifts in adaptive immune response were detected for different mucosal compartments, i.e., in subjects who suffered from severe or moderate-to-severe COVID-19, salivary sIgA levels were significantly higher than those in the control group (p < 0.05 and p < 0.005, respectively). An inverse correlation was demonstrated between the levels of total sIgA in all mucosal sites, and the number of days from the onset of disease to the start of study (r = 0.278, р < 0.05). When compared to the control subjects, all the patients with prior COVID-19 had significantly higher levels of total IgG in the induced sputum samples. Total IgG in saliva was also higher in the group of patients who had severe infection (p < 0.05). By contrast, IgG levels in nasopharyngeal samples were decreased in severe and moderately severe groups compared to the control group, thus, probably, indicating an immunodeficiency state in these cases. A direct significant correlation was also detected between the levels of total IgG in all studied samples and the levels of specific IgG antibodies against SARS-CoV-2 in the serum.

Long-term changes in the humoral mucosal immune response were most pronounced in the healthcare workers with a history of severe or moderate-to-severe COVID-19.

Russian Journal of Immunology. 2023;26(4):633-640
pages 633-640 views
Approaches to correction of immune system disturbances in post-COVID patients
Dobrynina M.A., Zurochka A.V., Zurochka V.A., Ryabova L.V., Sarapultsev A.P.

SARS-CoV-2 virus can induce immune system disorders in post-COVID patients, which may persist for an extended period beyond the acute phase of the disease. Therefore, the search for immunocorrection approaches to address the detected disorders is a significant challenge in clinical immunology. This study aimed to investigate the impact of a synthetic peptide derived from the active center of GM-CSF on the immune system of patients with post-COVID immunopathological syndrome. A total of 21 patients who previously suffered with SARS-CoV-2 infection were included in the study. Flow cytometry was used to analyze various immune cell populations, including panleukocyte markers for gated lymphocytes (CD45+ and CD46+), T lymphocytes (CD3+), helper inducers (CD3+, CD4+), cytotoxic T lymphocytes (CD3+, CD8+), TNK cells (CD3+, CD56+), natural killer cells (CD3-, CD56+), B lymphocytes (CD3-, CD19+), activated helper cells (CD3+, CD4+, CD25+), and activated T lymphocytes (CD3+, HLA-DR). Moreover, IgA, IgM, IgG antibodies specific to SARS-CoV-2, phagocytosis and NBT activity of neutrophils, and complement fragments C1q, C3a, and C5a were assessed. The results demonstrated that topical application of the synthetic peptide derived from the active center of GM-CSF (Acegram-spray) upon mucous membranes significantly influenced the functional bactericidal activity of neutrophils (NBT-activity), increased the percentage of T helper cells, and elevated the C3a complement fragment. These findings indicate that the synthetic peptide primarily affects innate immunity factors. However, no significant differences were observed in other immune system parameters. Therefore, the development of therapeutic approaches for post-COVID patients with impaired immune systems may require a search for additional immunomodulators that target T, B, and NK cells. Further research is needed to explore the effects of various immunomodulators on the immune system of post-COVID patients.

Russian Journal of Immunology. 2023;26(4):641-646
pages 641-646 views
Positive effects of recombinant interferon α2b on the phenotype of CD16+INFα/βR1-CD119+, CD16+INFα/βR1+CD119- neutrophil granulocyte subset in patients with post-COVID syndrome and herpesvirus infections
Atazhakhova M.G., Nesterova I.V., Chudilova G.A., Matushkina V.A., Kovaleva S.V., Chapurina V.N.

Post-COVID syndrome (PCS) is a multisystem inflammatory condition with manifestations of chronic fatigue syndrome (CFS) and cognitive disorders (CD), along with reactivation of chronic herpesvirus infections (HVI). The PCS manifestations require studying the molecular mechanisms associated with the production of IFN and receptor functions of neutrophil granulocytes (NG), which is relevant and promotes the search for immunotherapeutic strategies in patients with PCS. Our objective was to study the in vitro effects of recombinant interferon α2b (recIFNα2b) on the phenotype of CD16+IFNα/βR1-CD119+, CD16+IFNα/ βR1+CD119+ subsets and functional activity of NG in patients with post-COVID syndrome and herpesvirus infections. Materials and methods: 45 patients (24-60 years old) with PCS and HVI (HSV 1, EBV, HHV6, CMV) comprised the study group 1 (SG1). A questionnaire was conducted to assess the severity of PCS symptoms using a point scale. We performed a study of the content and phenotype of NG subsets, i.e., the CD16+IFNα/βR1-CD119+, CD16+IFNα/βR1+CD119-, CD16+IFNα/βR1+CD119+ subpopulation, phagocytic and NADPH oxidase function of NG before and after in vitro incubation with recIFNα2b (50 IU/ µL, for 60 min, at 37 °C) in the study group 1a (SG1a). The comparison group (CG) of 30 volunteers examined during the pre-COVID period. Results: We revealed more pronounced clinical manifestations of CFS and CD in SG1 patients with mixed HVI, than in mono-HVI cases. Increased expression density of all receptors was registered on CD16+IFNα/βR1+CD119-NG and CD16+IFNα/βR1-CD119+ NG, thus suggesting the NG activation with initiation of cytotoxicity or NETosis, a decrease in phagocytic function and intensity of NADPH oxidase activity with depletion of NG reserve capacity in SG1. We have obtained some data on the positive effect of recIFNα2b in vitro (SG1a), e.g., decreased CD16 expression density and enhancement of IFNα/βR1 receptor expression in the CD16+IFNα/βR1+CD119- subset. In the CD16+IFNα/βR1-CD119+ subset, we have found persistence of increased MFI CD16 and MFI CD119 receptors, restoration of defective NG phagocytic function and reduced excessive activity of NADPH oxidases. Conclusion: The positive effects of the recIFNα2b influence on deficient function of NG in PCS patients suggest an oppoptunity of using immunotherapy with a recIFNα2b-based drug, combined with highly active antioxidants for treatment of various PCS manifestations including CFS, CD, HVI, thus, probably, ensuring adequate functioning of antiviral and regulatory mechanisms of the immune system.

Russian Journal of Immunology. 2023;26(4):647-656
pages 647-656 views
Secretory IgA in patients with COVID-19 at different regimens of using multicomponent vaccine Immunovac-VP-4
Kostinov M.P., Abramova N.D., Osiptsov V.N., Tatevosov V.R., Gainitdinova V.V., Kryukova N.O., Baranova I.A., Khromova E.A., Korovkina E.S., Chuchalin A.G., Svitich O.A., Mashilov K.V.

The mucosal immunity performs an important function in prevention of respiratory infections including COVID-19. The search for approaches to activate the synthesis of post-infectious antibodies by correcting the factors of innate and adaptive immunity at mucous membranes of respiratory tract in patients with infection caused by the new coronavirus may be relevant for the treatment of patients with COVID-19. The aim of our study was to assess the concentrations of sIgA in the upper respiratory tract in patients with a confirmed diagnosis of Coronavirus infection caused by the COVID-19, and to evaluate the effect of an immunostimulating drug of bacterial origin upon the sIgA secretion.

The patients were divided into two groups: group 1 (n = 45), received basic therapy; group 2 (n = 33), in addition to basic therapy, received the bacterial vaccine Immunovac-VP-4 according to a combined scheme. The biomaterial sampling was carried out by scraping of epithelial cells from the nasal mucosa, pharyngeal scraping and salivary gland secretion on days 1, 14 and 30 of the study. sIgA levels in all biological fluids were studied using ELISA technique (JSC Vector-Best, Russia).

14 days after the start of observation, the dynamics of sIgA levels in nasal scrapings in group 1showed a significant decrease relative to the baseline values (p = 0.02), whereas the level of sIgA remained unchanged during the specified period (p = 0.07) in the group of patients receiving, along with basic therapy, additional Immunovac-VP-4 treatment. The dynamics of sIgA level in pharyngeal scrapings in the group of patients receiving only basic therapy did not change throughout the study period. Menwhile, the group of patients receiving basic therapy supplemented with Immunovac-VP-4 showed a significant increase in sIgA levels by the 30th day of follow-up over the baseline values (p = 0.02). The level of sIgA in salivary gland secretions did not differ significantly between the study groups during the entire follow-up period.

The results of our study showed that, in order to assess the state of mucosal immunity in patients with COVID-19, one may recommend determination of sIgA in nasal secretions. The Immunovac-VP-4 prescribed in complex therapy is accompanied by an increase in the sIgA levels at the mucous surfaces of the respiratory tract.

Russian Journal of Immunology. 2023;26(4):657-664
pages 657-664 views
Comparison of immune response to various SARS-CoV-2 vaccines within 6 months after starting vaccination and following revaccination
Astrakhantseva I.V.

The pandemic of coronavirus infection (COVID-19) has stimulated the development, testing and widespread use of preventive vaccines based on various platforms. Our aim was to perform a direct comparison of immunogenicity of various vaccines within a single study in small groups within six months of SARS-CoV-2 vaccination and revaccination.

The stdy group included subjects vaccinated with Sputnik V adenovirus vaccine, mRNA vaccines, and CoviVac whole-virion vaccine. Their immune status was assessed by enzyme immunoassay as specific antibody levels. Moreover, the neutralizing ability of detected antibodies was assessed using a cell test system based on pseudoviral technology.

All of the mentioned vaccines were shown to elicit an immune response against SARS-CoV-2 RBD antigen, however, appropriate antibody titers and neutralizing capacities differed depending on the type of vaccine. The mRNA vaccines proved to be the most immunogenic, the effectiveness of the immune response to the Sputnik V adenovirus-based vaccine was lower. However, 6 months after vaccination, the effectiveness of virus neutralizing antibodies induced by these vaccines did not differ. The whole-virion CoviVac vaccine with proven efficiency by independent epidemiological studies, induced an antibody response against the RBD protein to a lesser extent.

The seropositive participants of the study, both previously exposed to COVID-19 disease or vaccinated, exhibited high-titer production of antibodies already after the first dose of the Sputnik V vaccine, and a significantly higher antibody titer 6 months after the booster immunization as compared with initial level of antibodies, along with direct correlation between the antibody titers and their neutralizing activity.

Russian Journal of Immunology. 2023;26(4):665-670
pages 665-670 views
Efficiency of combined postoperative treatment including an immunomodulatory Hexapeptide in children with acute destructive pneumonia
Chapurina V.N., Nesterova I.V., Chudilova G.A., Kovaleva S.V., Lyagusha D.E., Teterin Y.V., Barova N.K., Tarakanov V.A.

Acute destructive pneumonia (ADP) is a severe purulent and septic infectious disorder of childhood, characterized by a high level of morbidity and associated with imbalance of the immune system (IS). Hence, there is an obvious need to study the immunopathogenesis of this disease in order to develop new therapeutic strategy aimed at eliminating the pathogen, detoxifying the body, relieving respiratory failure and correcting functional immune deficiency. Our aim was to perform a clinical and immunological study in order to evaluate efficiency of immunomodulatory therapy using a medical drug with hexapeptide as an active substance. This drug was included into the complex postoperative treatment of children with acute destructive pneumonia. Clinical and immunological examination of 15 children 2-5 years old with ADP was performed before (study group 1 – SG1) and after (study group 1a – SG1a) combined postsurgical treatment including immunomodulatory therapy with a Hexapeptide-based pharmaceutical (HP, Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine). Comparison group (CG) included twenty healthy children. The contents of T and B lymphocytes, natural killer cells (NK) were measured by means of flow cytometry (CYTOMICS FC 500, USA). Serum levels of IgA, IgM, IgG (ELISA), phagocytic and microbicidal activity of neutrophil granulocytes (NG) were also evaluated. Prior to the treatment in SG1 patients, a decreased number of CD3+CD19-T lymphocytes, CD3+CD8+ TCTL lymphocytes was revealed along with significant decrease in the contents of CD3-CD16+CD56+ NK (p1-3 < 0.05). It was found that in children with ADP, the IgG level did not differ from indices of control group, with a decrease of IgM (p1, 2 > 0.05), and increased level of IgA (p < 0.05). We have also found a deficiency of NG effector functions, i.e., insufficiency of active phagocytic NG with impaired capture and killing of bacterial antigen. Assays of NADPH-oxidase activity showed lacking response to both inflammation and additional induction by S. aureus. After complex treatment including immunomodulatory therapy in the SG1a group, we revealed a recovery in CD3+CD19-T lymphocyte contents, CD3+CD8+TCTL lymphocytes, CD3-CD16+CD56+ NK (p1-3 < 0.05). The trends towards normalization of IgA, IgM, improved NG effector functions (killing ability) were revealed due to activation of NADPH-oxidases. The restoration of immunological parameters in ADP was associated with earlier recovery from the purulent-destructive process in lungs, absence of postoperative complications including the prevention of septic process. The clinical and immunological effects of the immunomodulatory therapy program with HP-based pharmaceutical preparations suggest its potential usage during postoperative period in immunocompromised children with ADP.

Russian Journal of Immunology. 2023;26(4):671-678
pages 671-678 views
Clinical and immunological efficacy of the immunomodulating hexapeptide arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine in the complex postoperative treatment of children with acute osteomyelitis
Chudilova G.A., Chicherev E.A., Teterin Y.V., Chapurina V.N., Tarakanov V.A., Barova N.K., Nesterova I.V.

The recurrent and persistent nature of osteomyelitis, like as associated high morbidity of patients, prolonged hospitalization and expensive treatment require development of new approaches in therapy and pathogenetic justification of the immunotropic drugs usage in complex etiopathogenetic treatment of this disorder. Our objective was to evaluate the clinical and immunological efficacy of hexapeptide (HP), arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine implemented in the complex treatment of acute osteomyelitis in children during the postoperative period. 19 children aged 8-15 years with acute osteomyelitis (AOM) were studied: the study group 1 (SG1, n = 11) received a standard treatment at all the disease stages; in study group 2 (SG2, n = 8), the standard therapy was supplemented with a medical drug Imunofan, containing hexapeptide (НP) as the active substance. Prior and after the course of drug treatment, we determined the following parameters: the contents of T cells (CD3+CD19-, CD3+CD4+, CD3+CD8+, CD3+CD4+/CD3+CD8+) and B cells (CD3-CD19+), NK (CD3-CD16+CD56+) by means of Cytomics FC-500 (“Веckman Coulter”, USA), the levels of serum IgA, IgM, IgG (ELISA tests), assessment of phagocytic activity of neutrophil granulocytes (NG) with determining the ratio of actively phagocytic NG (%PhAN), capture processes (PhN, PhI) and the completeness of phagocytosis (%D, DI) tested with S. aureus (strain No. 209). In the studied groups with AOM, a decreased content of T lymphocytes, T helper cells, T lymphocytes, NK cells was revealed, along with unchanged content of B lymphocytes. In SG2, the increased IgA and IgG levesl have been shown. We have also revealed a deficiency of phagocytic function associated with the processes of phagocytosis completion. The use of immunomodulatory therapy with an HP-containing pharmaceutical drug in combination with standard treatment was associated with restoration of immunological parameters to the reference values of healthy children, thus leading to shorter febrile period, milder manifestations of intoxication, earlier periods of reconvalescence from purulent-inflammatory process, and reduced hospital stay. The obtained positive clinical and immunological effects demonstrate the expediency of targeted immunomodulatory therapy including a pharmaceutical HP-containing drug as the active substance in the complex postoperative treatment of children with AOM. Restoration of the disturbed mechanisms of anti-infectious immunity in AOM under usage of immunomodulating HP contributes to more effective elimination of pathogens and, as a result, improvement of the clinical course of the disease, as well as prevention of chronic inflammatory processes and aggravation of immune system dysfunction.

Russian Journal of Immunology. 2023;26(4):679-688
pages 679-688 views
In vitro effects of recombinant IFNα2B on the content of antigen-presenting CD66b+CD16+CD33+HLA-DR+ subset of neutrophils in children with acute osteomyelitis
Nesterova I.V., Chudilova G.A., Teterin Y.V., Chicherev E.A., Chapurina V.N., Tarakanov V.A., Barova N.K.

Negative impact of S. aureus, seems to be a sufficient condition for the spread of the infectious process in the bone in acute osteomyelitis (AOM) due to its altered elimination caused by dysfunction of the immune system (IS), in particular, of neutrophilic granulocytes (NG). Correction of NG dysfunction in AOM under the influence of immunotropic substances and cytokines via modulation of the NG phenotypic subsets is of sufficient interest. Our aim was to evaluate the in vitro effects of recombinant IFNá2b on the number and phenotype of CD66b+CD16+CD33+HLA-DR-, CD66b+CD16+CD33+HLA-DR+ subsets and on phagocytic function of neutrophilic granulocytes in acute osteomyelitis in children.

The study of peripheral blood (PB) samples from children aged 8-15 years was carried out as follows: patients with АOM (n = 24) comprised study group 1 (SG1), healthy children (n = 13) were included into comparison group (CG). PB samples of children with AOM were incubated with recIFNá2b (50 IU/µL, 60 min, 37 °C.) in the study group 1a (SG1a). Before and after incubation with recIFNá2b, the number of NG subsets CD66b+CD16+CD33+HLA-DR-, CD66b+CD16+CD33+HLA-DR+ and the density values of receptor expression by fluorescence intensity (MFI) were also determined (FC 500, Beckman Coulter, США). Phagocytic activity of NCs was evaluated as the contents of actively phagocytic NCs (%PhAN), volume of the engulfed S. aureus (strain 209) by assessing their phagocytic number (PhN), phagocytic index (PhI). Bacterial killing was determined as the percentages of microbe digestion (%D), digestion index (DI).

The cells from AOM patients revealed a subset expressing the HLA-DR receptor – СD66b+CD16+CD33+HLA-DR+NG, which is absent in the PB of CG children. The cells with primed phenotype exhibited an increased expression density of activation receptors CD16 and CD66b. Incubation of PB in AOM with recIFNá2b led to an increased proportion of CD66b+CD16+CD33+HLA-DR+ NG subset which showed active phagocytosis and improved digestion processes. The present study shows the emergence of activated subset of “long-lived” CD66b+CD16+CD33+HLA-DR+ NCs in children with AOM. This subpopulation has APC features, by presenting AG to T lymphocytes, with preserved effector properties. In an in vitro experimental system, a positive effect of recIFNá2b was demonstrated, leading to an increased number of NGs of the CD66b+CD16+CD33+HLA-DR+ subset and recovery of S. aureus phagocytosis by NGs, thus being promising in the future for development of new approaches to optimization of complex therapy in the postoperative period of AOM treatment, prevention of complications and the opportunity to alleviate the disorders in the immune system.

Russian Journal of Immunology. 2023;26(4):689-696
pages 689-696 views
Clinical and immunological efficacy of immunomodulating hexapeptide associated with the restoration of CD11b+CD64-CD32+CD16+ and CD11b+CD64+CD32+CD16+ neutrophil granulocytes subset in women with chronic infectious and inflammatory diseases of the pelvic organs
Kovaleva S.V., Nesterova I.V., Chudilova G.A., Pikturno S.N., Lomtatidze L.V.

Failure of anti-infectious immune protection is considered a reason for the prolonged course and recurrence of chronic infectious and inflammatory diseases of pelvic organs (PID). Our aim was to evaluate the effect of an original hexapeptide (HP) on negatively altered subpopulations of neutrophil granulocytes (NG) CD11b+CD64-CD32+CD16+ and CD11b+CD64+CD32+CD16+, their phenotype and associated effector functions in immunocompromised women with PID.

35 women (20-40 years old) with PID were studied during the period of clinical exacerbation (study group 1, SG1). Study group 1a (SG1a) consisted of patients who underwent treatment including the HP injections (45 mcg/ mL, 1 ml intramuscularly once a day for 10 days). The comparison group (CG) consisted of 20 conditionally healthy women. The numbers of CD11b+CD64-CD32+CD16+NG and CD11b+CD64+CD32+CD16+NG cell subsets and the density of receptor expression, phagocytic and microbicidal function of NG were determined.

In SG1, decreased counts of the major NG subpopulation (CD11b+CD64-CD32+CD16+NG) was revealed (p < 0.05), with a trend for increase of minor subset CD11b+CD64+CD32+CD16+NG (p > 0.05). In the CD11b+CD64-CD32+CD16+NG subset, we noted a decreased expression of CD16 (1.4-fold), CD11b (2-fold) (p1, 2 < 0.05). In the minor subset CD11b+CD64+CD32+CD16+NG, the expression densities were decreased in CD16 (1.7-fold), CD11b (2.1-fold, p1, 2 < 0.05). At the same time, the phagocytic and microbicidal functions of NG were found to be decreased. In the course of immunomodulatory therapy with the HP-based drug, positive changes in immunological parameters were revealed. In SG1a, an increased number of major NC subset was observed, with an increase in the expression density of CD16 by 1.2 times, CD11b by 1.7 times relative to SG1 (p1, 2 < 0.05). The contents of minor NG subset tended to decrease, along with CD16 expression density reaching the indices of comparison group. CD11b increased 1.3 times relative to SG1 (p < 0.05). Higher ratios of actively phagocytizing NG and their killing ability have been registered. Clinically, we observed faster regression of clinical PID exacerbation symptoms and decreased frequency of relapses 6 months after treatment in 88.6% of cases. The positive immunomodulatory effects of the HP-based drug upon altered subsets of CD11b+CD64-CD32+CD16+ and CD11b+CD64+CD32+CD16+ NGs, their phenotype and associated effector functions suggest an opportunity of its usage for the correction of NG dysfunctions in immunocompromised women with PID, thus providing stable clinical and immunological remission and protective effect.

Russian Journal of Immunology. 2023;26(4):697-704
pages 697-704 views
Clinical and immunological efficacy of intranasal interferon in the post-vaccination period in patients vaccinated against SARS-CoV-2 coronavirus
Savin T.V., Tyurina T.O., Milichkina A.M., Drozd I.V., Kuznetsova R.N., Simbirtsev A.S., Totolyan A.A.

The COVID-19 pandemic, caused by SARS-CoV-2, remains one of the actual medico-social issues of today's world. Novel coronavirus infection officially listed in dangerous infections. When an ingress of coronavirus infection in the background of intensive production of inflammatory inducers comes with decreased levels of type I interferon that cause loss of protective abilities of the body against the background of the destruction of its own tissues. Herd immunity development via vaccination increases the proportion of people with protective immunity against SARS-CoV-2 is an important factor in stopping the spread of the infection. However, during the first days after vaccination, patients remain susceptible to possible infection. A promising prophylactic agent is interferon-containing drugs widely used in Russia and CIS countries for the prevention and treatment of viral infectious diseases, in particular SARS and influenza. Our study showed that intranasal recombinant IFNα-2b has clinical and immunological efficacy after two courses of the drug (within 5 days after V1 and after V2 vaccination with the EpiVacCorona vaccine).

Russian Journal of Immunology. 2023;26(4):705-712
pages 705-712 views

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