ISSN (print): 1028-7221, ISSN (online): 2782-7291 Founders: Nataliya K. Gorlina, Ivan G. Kozlov, Anatoliy N. Cheredeev Editor-in-Chief: Valery A. Chereshnev, academician of RAS, Doctor of Sc., Professor Frequency / Access: 4 issues per year / Open Included in: White List (4th level), Higher Attestation Commission List, RISC, Scopus
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Analysis of clonal NK cell populations using single-cell transcriptomics data
Natural killer (NK) cells represent a critical component of antiviral immunity, demonstrating remarkable adaptability during infections such as human cytomegalovirus (hCMV) and SARS-CoV-2. Recent advances in single-cell transcriptomics have revealed the clonally expanding NK cell populations with distinct functional profiles, blurring the traditional boundaries between innate and adaptive immunity. However, the functional heterogeneity and immunological significance of these clones remain incompletely understood. Our aim was to dissect clonal NK cell heterogeneity using published scRNA-seq datasets from hCMV-seropositive, seronegative, and COVID-19 patients, focusing on cluster-specific gene expression patterns. Our computational pipeline employed Seurat-based integration and high-resolution clustering of datasets from hCMV-seropositive (n = 5) and seronegative (n = 2) donors, along with COVID-19 patients (n = 2). We analyzed datasets using Seurat 5 in R. Quality-controlled data were normalized (SCTransform), integrated (batch-corrected), and clustered (UMAP). Differential gene expression (Wilcoxon test, log2FC > 0.25, p-adj < 0.05) and annotation were performed. In hCMV-seropositive individuals, we identified 12 transcriptionally distinct NK cell clusters exhibiting KLRC2 (NKG2C)-dependent organization, with specific clones showing either enhanced cytotoxic potential (marked by GZMB/GZMA upregulation), or unique inhibitory receptor profiles (variable KIR expression patterns). The hCMV-seronegative cohort displayed a simpler clonal structure with 9 clusters showing reduced KIR diversity but maintained distinct effector gene signatures. Analysis of COVID-19 patients revealed divergent clonal patterns: one patient showed reduced KLRC2 variability with prominent KLRC1 (NKG2A) expression, while another exhibited KIR heterogeneity without KLRC2 variation. Our analysis reveals distinct clonal NK cell populations in hCMV and COVID-19 contexts, characterized by divergent expression of activating and inhibitory receptors. These findings demonstrate infection-specific dynamics of clonal NK cell populations, highlighting their adaptive potential through differential receptor expression in antiviral responses.
版权所有 © Ustiuzhanina M., Kovalenko E., 2025 https://creativecommons.org/licenses/by/4.0
In vitro positive modification of effector functions and subsets of CD64+CD32+CD16+CD11b+ and CD64-CD32+CD16+CD11b+ neutrophil granulocytes from immunocompromised patients with immunosenescence induced by arginyl-α-aspartyl-lysyl-valyl-tyrosyl-arginine
The increasing proportion of elderly and senile individuals in human population causes a problem of age-associated diseases, with immunosenescence playing a key role. Neutrophil granulocytes (NG) are largely susceptible to this process, which requires studying changes in their functioning during immunosenescence and developing methods for experimental correction of NG dysfunctions. Our objective was to clarify the nature of NG dysfunctions during immunosenescence, and to evaluate the effect of synthetic thymic hexapeptide (HP) on the effector functions and CD64+CD32+CD16+CD11b+ and CD64-CD32+CD16+CD11b+ subsets of NG in elderly and senile individuals. The study involved 15 immunocompromised patients aged 60-78 years with chronic obstructive lung disease (COPD), with prolonged and frequent exacerbations (study group 1, SG1), and 30 conditionally healthy volunteers aged 60-74 years (comparison group, CG). We have evaluated the NG subsets (%), i.e., cell subpopulations with CD64, CD32, CD16, CD11b receptors, expression density of these receptors (MFI), phagocytic and microbicidal functions of NG in intact peripheral blood (SG1) and after incubation with tested hexapeptide (10-6 g/L) for 60 minutes at 37 °C (SG1a). We have revealed an increased contents of CD64+CD32+CD16+CD11b+NG subset and a reduced content of the CD64-CD32+CD16+CD11b+NG subset in SG1 patients in comparison to comparison group, an increased density of CD16 expression along with decreased density of CD11b expression on NG of both subsets. Moreover, an impairment in phagocytic and NADPH-oxidase activity of NG was determined in SG1. Under the influence of the hexapeptide, we have noted a pronounced effect, i.e., a decreased content of CD64+CD32+CD16+CD11b+NG and increased number of CD64-CD32+CD16+CD11b+NG, higher MFI of CD11b on NG of both subsets, digestive functions, stimulated NADPH oxidase activity. The average effect was determined as a decreased MFI of CD16, and an increase in actively phagocyting NG. Low-level effect was registered by the absorption processes, and spontaneous NADPH-oxidase activity of NG. Positive modification of NG functioning under the influence of hexapeptide was shown in vitro upon incubation of NG from immunocompromised patients with immunosenescence.
版权所有 © Kovaleva S., Poezzhaev E., Teterin Y., Pikturno S., 2025 https://creativecommons.org/licenses/by/4.0
HER2-CAR-NK cells exhibit enhanced cytotoxic activity towards HER2-positive tumors
Targeting of adoptive immune cells is among modern approaches to therapy of solid tumors. Expression of an epidermal growth factor receptor HER2 is a common finding (20% of breast tumors) and is associated with a negative outcome. In this regard, obtaining HER2-specific effector cells carrying a chimeric CAR receptor is a relevant task. NK cells have a wide spectrum of activating receptors capable of recognizing tumor-associated markers and do not initiate a graft-versus-host reaction. The goal of this study was to obtain effector CAR-NK cells capable of eliminating the HER2-positive tumor targets. The NK cells were obtained by negative magnetic separation from peripheral mononuclear cells isolated from volunteers’ blood using density gradient centrifugation. Activated NK cells were modified by retroviral transduction. Preliminarily transfected Phoenix Ampho cells were used to accumulate retroviral particles carrying HER2- CAR construct. The DARPin 9-29-HER2 molecule with affinity for the HER2 distal domain I was used as the antigen-recognizing domain. The proportion of transduced NK cells was measured by means of GFP reporter protein expression. The surface emergence of HER2-CAR receptors was detected by expression of the c-Myc extracellular domain. All modified GFP+NK cells were capable of expressing HER2-CAR receptors on the cell membrane. Functional activity of HER2-CAR NK cells was measured using flow cytometry, by degranulation intensity and IFNγ production in the presence of HER2-positive target cells BT-474. To assess lytic activity of HER2-CAR NK cells, the cultures of HER2-CAR-expressing GFP+NK cells and unmodified GFP-NK cells were obtained by cell sorting. Lysis of BT-474 targets was measured by calcein release upon incubation with HER2-CAR and GFP- effectors. HER2-CAR NK cells were characterized by higher levels of degranulation and IFNγ production compared to GFP-NK cells. Moreover, HER2-CAR-NK cells had higher lytic activity towards BT-474. Thus, by means of genetic modification based on primary NK cells, we obtained highly effective HER2-CAR-NK agents capable of HER2-positive target recognition and possessing cytotoxic and cytokine-producing potential in presence of tumor cells. Expanding the variety of cellular effectors aimed at treating HER2-positive breast tumors will increase the potential of personalized tumor therapy in the future.
版权所有 © Alekseeva N., Streltsova M., Vavilova Y., Deyev S., Kovalenko E., 2025 https://creativecommons.org/licenses/by/4.0
Сell-free DNA in blood of mice with Th1- and Th2-dependent variants of chronic graft-versus-host disease
According to current concepts, the levels of extracellular DNA (cfDNA) in patients with various disorders may significantly depend on the severity of their systemic inflammation. Predominance of Th1- or Th2-dependent immune responses during the disease development is directly related to the mechanisms of emerging inflammatory process. The aim of this work was to study the effect of Th1/Th2 balance on the cfDNA levels in blood of experimental animals using an animal model chronic graft-versus-host disease (cGVHD). This condition was induced by transferring lymphoid cells from DBA mice to the first-generation hybrid mice (C57Bl/6xDBA/2)F1. In a subgroup of animals, the predominance of Th1-dependent variant led to a pronounced immunodeficiency state. In other subgroup, this immunological disorder manifested as a Th2-dependent variant, ultimately resulting in the formation of immune complex glomerulonephritis. Cell-free DNA (cfDNA) was measured at different time points during the development of cGVHD. We have shown that in a subgroup of mice, an increased level of plasma cfDNA was observed as soon as at early stages upon induction of cGVHD, whereas the contents of cell membrane-associated cfDNA remained unchanged. By the time of registering clinical outcomes of cGVHD, in the case of the Th1-dependent variant, the concentrations of cfDNA do not differ from appropriate values in the animals subjected to syngeneic transplant. The data obtained suggest that the dominance of Th1 lymphocyte activity does not lead to increased cfDNA level in murine blood. In another group of animals, with a predominance of the immunopathology developing via Th2-dependent pathway, a significantly increased level of cfDNA in blood is found, apparently, due to development of immune complex-associated glomerulonephritis. Thus, the preceding dominance of Th2 lymphocyte activity does not prevent the occurrence of nephritis, accompanied by increased cfDNA levels.
版权所有 © Gavrilova E., Goiman E., Demchenko E., Volskiy N., 2025 https://creativecommons.org/licenses/by/4.0
Effect of enriched environment on spatial memory and expression of microglial activation markers in Balb/c mice
Enriched habitat of laboratory animals causes stimulation of neuronal plasticity including increased level of hippocampal neurogenesis and more efficient spatial orientation. In addition, the enriched environment has an immunomodulatory effect on both peripheral immune cells and microglia, i.e., resident brain macrophages. Since immune cells and their secreted products modulate the processes of neuronal plasticity, studying the effects of enriched environment is relevant on the level of neurogenesis in rodents with different immune status. Compared with C57Bl/6, Balb/c mice are characterized by predominance of humoral (Th2) rather than cellular (Th1) types of immunity which is associated with differences in the H2 region of the major histocompatibility (MHCI) gene locus, as well as a higher level of anxiety revealed by behavioral phenotyping. The aim of our study was to evaluate the effect of enriched environment on spatial memory, levels of neurogenesis, and activation features of resident macrophages (microglia) in hippocampus of Balb/c mice. The study was performed on 4-month-old female Balb/c mice. To assess the spatial memory and learning ability, the Barnes labyrinth was used. Gene expression levels were assessed by means of gene-specific PCR using primers for BDNF, CD68, DCX, FGF2, IBA1, IL-1B, IL-10, SOX2, TMEM119, TNFα; GAPDH was used as a reference gene. The obtained data suggest that keeping Balb/c mice under the enriched conditions promotes increased levels of hippocampal neurogenesis, along with more efficient spatial orientation. Expression of genes encoding neurotrophic factors, as well as cytokines and markers of microglia activation proved to be increased for FGF2, TNFα, Iba1 and TMEM119, whereas expression of BDNF, IL-1β, IL-10 and CD68 genes did not change. Hence, expression of BDNF and IL-10 genes in Balb/c mice from enriched environment was not increased, being typical for C57BL/6 mice. However, it does not prevent the proliferation and differentiation of neurons in gyrus dentatus and successful spatial orientation in Barnes labyrinth. Microglial cells in Balb/c mice under enriched conditions are probably polarized according to the M0/M2 type.
版权所有 © Lebedeva T., Kurilova E., Sidorova M., Tuchina O., 2025 https://creativecommons.org/licenses/by/4.0
Assessing effects of an antigen complex from opportunistic bacteria on activation of CD54 receptor expression by human promonocytic U937 cell line
Opportunistic pathogens play an important role in development of respiratory infections, causing high morbidity and mortality rates. A promising approach is the use of antigen-based drugs from opportunistic bacteria that stimulate the immune system. Search for appropriate assay techniques and biomarkers of immune response is an important task in their development. Potential stimulation of myeloid cells is of particular interest for these purposes. The U937 cell line is widely used as a model for analyzing the functional activity of monocytes and macrophages, being derived from human histiocytic lymphoma cells and exhibiting promonocyte characteristics, The CD54 (ICAM-1) molecule is a surface glycoprotein that functions as an adhesion receptor and plays a key role in targeted migration of leukocytes from bloodstream to inflamed tissues. Under the inflammatory stimulation, expression of ICAM-1 increases significantly on the surface of immune cells, making it a potential activation marker in certain components of innate immune system, including U937 cell model. This study considered activation of CD54 (ICAM-1) receptor expression in human U937 promonocytic cells under the influence of two different antigen complex from opportunistic pathogens, supplied with immunostimulatory copolymer, or without its addition. The test antigen complex included antigens from four species of opportunistic bacteria: Escherichia coli, Proteus vulgaris, Staphylococcus aureus, Klebsiella pneumoniae. As an additional immunostimulating agent, a copolymer of 2-methyl-5-vinylpyridine and N-vinylpyrrolidone hydrochloride was used. Flow cytometry was applied in order to assess CD54 (ICAM- 1) expression on U937 cells, The cells were stimulated with peptidoglycan from S. aureus (positive control), and with mentioned variants of the antigen complex form opportunistic bacteria. The cell activity was evaluated using the activation coefficients, which reflected the increase in CD54 expression. The activation coefficient for positive controls was considered significant if it reached, at least, 50% (activation of cells by the reference antigen), whereas cell activation by the studied bacterial antigen complexes was considered significant at an activation coefficient of at least 30%. It was shown that both variants and the positive control induced a dose-dependent increase in CD54 expression. The optimal stimulation concentration was 25 µg/mL. These effects confirmed ability of the antigen complex from opportunistic pathogens to activate monocyte-macrophage cells and enhance the innate immune response. The obtained results emphasize the importance of using ICAM-1 as a marker of immune cell activation. The tested method seems to be promising in order to test effectiveness of drugs based on opportunistic bacteria.
版权所有 © Kalinichenko E., Kozyreva O., Sidorov N., Sorokina E., Mikhailova N., 2025 https://creativecommons.org/licenses/by/4.0
Alteration of IFNα and IFNβ gene expression by siRNA targeting the Nup98 gene during in vitro HSV-1 infection
Herpes simplex virus type 1 (HSV-1) is taxonomically classified as α-herpesvirus and is a complex double-stranded DNA virus. HSV-1 infections are extremely common among human population, with a global prevalence of 65% in persons under 50. In addition to labial and genital lesions, HSV-1-associated diseases include herpetic stromal keratitis, HSV encephalitis, and Alzheimer’s disease. Therefore, adaptive immune response is essential for controlling HSV infection, its reactivation, and complications. Key components of the adaptive immunity include IFNα and IFNβ, which play an important role at the early stages of infection caused by herpesviruses. Increased IFNα expression induces a systemic immune response, by activating NK cells, T lymphocytes, and increasing their migration to the inflammation site, as well as suppression of the viral life cycle by stimulating NK cell cytotoxicity and Th1 cell differentiation. Moreover, the main functions of IFNβ are to induce expression of interferon-stimulating genes (ISGs), whose expression products are able to inhibit viral reproduction cycle at various stages. A wide range of drug therapies and other approaches are currently used to treat herpes infections. Over time, however, an increased incidence of HSV-1 infection is observed in general population. In view of the current trends, it is necessary to search for new approaches aimed at reducing the incidence of HSV-1 infection and its complications. A promising approach may include usage of RNA interference effect, which underlies the action of potential new-generation antiherpetic drugs. RNA interference is a targeted inhibition of mRNA translation which entails disruption of subsequent protein biosynthesis. During its reproduction, HSV-1 imports viral DNA through the nuclear pore complex (NPC), located at the nuclear membrane. The NPC consists of nucleoporin proteins (Nup98, Nup205, NXF1 and others). Therefore, disruption of NPC structure resulting from miRNA-mediated inhibition of nucleoporin protein formation may hypothetically lead to a decreased HSV-1 reproduction.
版权所有 © Pashkov E., Kulikova L., Svitich O., Zverev V., 2025 https://creativecommons.org/licenses/by/4.0
Content of RANTES, IL-8 and MIP-1β chemokines in platelet lysates obtained from donor blood
Growth supplements obtained from animal sera have a rather variable range of a specific growth factor contents and are subject to potential contamination. Moreover, the growth supplements obtained from animal raw materials contain a composition of proteins, vitamins and microelements necessary for full-fledged cell growth, and one may overcome these drawbacks by replacing them with a product obtained from human donor blood. Platelet lysate contains biologically active molecules derived from endogenous granules of these blood elements. Concentration of distinct biocomponents in the resulting product is variable, depending not only on gender and blood group, but also on other, as yet unidentified individual characteristics. The aim of this study was to examine the content of some chemokines, in particular, RANTES, MIP-1β and IL-8, in platelet lysates obtained from healthy donors. The highest concentrations of MIP-1β cytokine were noted in Rh-negative donors, in females with blood group III, and in males with the IV. blood group. The highest IL-8 contents in platelet lysate were also recorded in Rh-negative, group IV men and women. Platelet lysate of volunteers with the II blood group (men, Rh-negative; women, Rh-positive) contained the highest amount of RANTES. Significant differences were found between the MIP-1β levels in thrombolysate of men and women with the second A (II), and AB (IV) Rh-negative blood groups; between women of the third B (III) blood group with different Rh factors. Moreover, statistically significant differences were found in the RANTES/CCL5 chemokine values in the thrombolysate for the groups of men and women with the second A (II) [with R (+) and R (-)], and AB (IV) blood group (Rh+). Interestingly, in Rh (-) men with the first 0 (I) and second A (II) blood groups, the content of chemokine RANTES/CCL5 in the blood thrombolysate significantly exceeded similar values in the blood obtained from Rh-positive men. Conclusion: The relationship between the donors’ belonging to a particular blood group and the content of these chemokines is not yet clear. Future studies with deep bioinformatics analysis will reveal the unclear interrelations between these indicators.
版权所有 © Shupletsova V., Melashchenko O., Gazatova N., Khaziakhmatova O., Minina A., Kopteva A., Kabanchuk N., Pervenetskaya T., Goncharov A., Litvinova L., 2025 https://creativecommons.org/licenses/by/4.0
Immune status and expression of HLA-E, HLA-G and HLA-DR molecules on conventional T lymphocytes in patients with multiple myeloma before and after autologous hematopoietic stem cell transplantation
Multiple myeloma (MM) is an incurable disease with common recurrence after treatment, including high-dose chemotherapy (HDC) followed by autologous hematopoietic stem cell transplantation (auto-HSCT). Tumor microenvironment is a factor of achieving long-term remission. Its immunosuppressive effects are mediated due to non-classical HLA class Ib molecules, i.e., HLA-E and HLA-G. These molecules interact with inhibitory receptors (NKG2A/CD94 for HLA-E; ILT2, ILT4, KIR2DL4 for HLA-G) on the surface of NK and T lymphocytes, blocking their cytotoxic activity and facilitating tumor evasion from immune surveillance. In contrast, the classical HLA-DR molecule plays an opposite role, enhancing antitumor immunity through the activation of CD4+T helpers. In this study, a comparative analysis of HLA-G/E/DR expression and counts of main immunocompetent cell populations (CD4+, CD8+, NK, NKT cells, B lymphocytes, monocytes) were performed by flow cytometry method in 10 patients with MM before and after HDC with auto-HSCT, and in 8 healthy volunteers. The results showed that, after therapy, the patients had a significant decrease of total CD3+T lymphocyte counts, including CD8+ and CD4+HLA-G+ subpopulations (p < 0.05), thus reflecting a cumulative immunosuppressive effect of melphalan-based conditioning. A decreased number of CD4+HLA-G+ cells, which have regulatory properties and are capable of suppressing the immune response, may indicate partial destruction of the tumor niche. At the same time, a paradoxically increased proportion of CD8+T lymphocytes, along with general lymphopenia, may be associated with clonal expansion of antigen-specific populations with “exhausted” T cell phenotype which requires further study. The results obtained suggest a dualistic role of HLA molecules in pathogenesis of MM: HLA-E/G act as key mediators of immunosuppression, while HLA-DR potentiates antitumor response. The discovered imbalance opens up new prospects for further studies of a role of HLA molecules in the tumor process, which may be applied to personalized therapy, including targeted blockade of NKG2A/LILRB1 receptors or HLA Ib molecules, and development of prognostic models based on a comprehensive analysis of HLA-G/E/DR expression.
版权所有 © Skachkov I., Aktanova A., Denisova V., Pashkina E., 2025 https://creativecommons.org/licenses/by/4.0
Methodological aspects of ex vivo-generated monocyte-derived microglia-like cells in children with autism
Current research findings suggest that dysregulation between the nervous and immune systems is a primary factor contributing to both initiation and progression of autism spectrum disorders (ASD). Microglia consists of resident brain immune cells playing a pivotal role in neuroinflammation and synaptic plasticity impairment. However, understanding these mechanisms has been limited by the lack of relevant experimental models. One promising approach involves microglia-like cells derived from peripheral blood monocytes (MDMi), which can serve as an effective model for studying human microglial function and developing personalized therapeutic strategies for neuropsychiatric diseases. The aim of our study was to optimize a protocol for generating sufficient quantities of microglia-like cells from peripheral blood monocytes of children with autism suitable for functional testing. Peripheral blood samples were collected from 18 children diagnosed with autism (mean age: 8.2 years; range: 6-12 years; 12 boys, 6 girls). Mononuclear cells were isolated using Ficoll density gradient centrifugation. After a 24-hour incubation period, adherent fractions enriched in monocytes were obtained via plate adherence. The monocytes were then cultured for either 10 or 14 days in serum-free RPMI-1640 medium supplemented with antibiotics and various cytokine cocktails to induce differentiation into MDMi. Viability was assessed using supravital staining with DAPI, while phenotyping was performed by flow cytometry targeting specific microglial markers such as P2RY12 and TMEM119. Statistical analyses were performed using PAST software version 4.03. Our findings demonstrate that successful induction of microglia-like cells requires, at least, a ten-day culture period with > 3 × 105 cells per well in RPMI-1640 medium containing stable glutamine, antibiotics, and a cocktail of three cytokines: GM-CSF, 10 ng/mL; IL-34, 100 ng/mL; IL-3, 10 ng/mL. Under these conditions, approximately 6 × 104 viable cells are generated, with over 90% expressing the microglial marker P2RY12. This cell population provides a valuable tool for studying ASD pathogenesis and identifying personalized treatment approaches.
版权所有 © Filippova Y., Rusakova K., Burmistrova A., 2025 https://creativecommons.org/licenses/by/4.0
Basic lymphocyte subsets during the post-traumatic period in children
Severe trauma remains a leading cause of disability and mortality among children over 1 year. This study aimed to assess the dynamics of peripheral blood lymphocyte subpopulations in pediatric trauma, depending on severity, complication risks, and general prognosis in pediatric trauma. A total of 118 children with severe mechanical trauma (ISS ≥ 16) were included. According to the Severe Injury Outcomes Scale (OISS), 60 patients had a favorable outcome; 51, with unfavorable outcome, and fatal outcome was documented in 7 cases. On the basis of clinical course, the subgroups with septic complications (PSC, n = 23) and multiple organ dysfunction syndrome (MODS, n = 19) were discerned. Flow cytometric analysis of lymphocyte subpopulations (CD3+, CD19+, NK cells) was conducted on days 1, 3, 5, 7, 10, and 14 post-trauma, with return to age-specific reference values. A comparison group included 34 children with mild or moderate trauma (ISS < 16), and a control group consisted of 60 age- and sex-matched healthy children. The laboratory findings revealed a significant and sustained reduction in CD3+, CD19+, and NK lymphocyte counts in children with severe trauma as early as day 1, with partial recovery by days 5-7. In children with mild trauma, these changes were less pronounced. Persistent lymphopenia, especially, in CD3+ and NK cells was significantly associated with MODS, PSC, and poor outcomes. These results confirm the prognostic relevance of dynamic monitoring of lymphocyte subpopulations as sensitive markers of immune dysfunction in the context of severe trauma and its complications. Inclusion of cellular immune parameters into risk stratification protocols may enhance the early identification of children at high risk for adverse outcomes and suggest targeted therapeutic interventions.
版权所有 © Zakirov R., Petrichuk S., Karaseva O., 2025 https://creativecommons.org/licenses/by/4.0
A family case of SOPH syndrome in children
Prevalence of SOPH syndrome in the Republic of Sakha (Yakutia) is slightly more than 18 patients per 100,000 Yakut population. Frequency of heterozygous state for the causal mutation is 1,300 per 100,000 healthy Yakuts. As of 2009, the prevalence of SOPH syndrome in the Republic of Sakha (Yakutia) for entire population was 4.53 per 100,000, and among Yakuts, 9.95 per 100,000. This article concerns two clinical cases of SOPH syndrome in a single family (brother and sister) observed for 6 years. This clinical example is of interest to pediatricians and family doctors practicing in the Republic of Sakha (Yakutia). We used outpatient cards of municipal polyclinics for 112,000 children at their residence place, observation cards for children at the Consultative Polyclinic No.1 at the National Center of Medicine. The phenotype of both children is similar. When looking for dysplastic features, we revealed brachycephalic skull, symmetrical face, hypomimia, straight nose with protruding glabella, slight exophthalm, hypoplastic cheekbones, long filter, thin lips, uneven dentition. The skin was dark and dry. Micromelia was also documented, along with short chest and enlarged belly. The limbs were symmetrically shortened. Sex features were by male type. Stools and diuretic functions were normal. Both children underwent radiography of their hands. The delayed bone growth was revealed in both children. Both children underwent KREC and TREC studies and genetic testing. Both children were homozygous for 5741G>A mutation in NBAS gene. Immunograms of both children showed a sharp decrease in IgA, IgM and IgG levels. Both children were administered regular replacement therapy with subcutaneous injections of normal human immunoglobulin. Cutaquig preparation has been also prescribed at a monthly dose of 0.5-0.6 g/kg, according to the protocol (4 g every 10 days, at two subcutaneous injection points). Currently, the children are receiving substitution therapy at their place of residence. These cases are of interest to practitioners and scientists, due to similar gene mutation in brother and sister. One should evaluate clinical course in all cases of SOPH syndrome in order to develop appropriate clinical recommendations. Establishment of the SOPH-syndrome registry in Republic of Sakha (Yakutia) will help in providing medical drugs and medical care to children with this type of primary immunodeficiency.
版权所有 © Ivanova O., Ivanova I., 2025 https://creativecommons.org/licenses/by/4.0
Laboratory criteria for improving the diagnosis of autoimmune hepatitis and Wilson’s disease in children
Specification of laboratory criteria for improving differential diagnostics of children with autoimmune hepatitis (AIH) and Wilson’s disease (WD) is a relevant task in pediatrics. Increased titers of antinuclear factor (ANF) in blood serum is among laboratory criteria for diagnostics of AIH. Some WD cases have been described which can manifest as autoimmune hepatitis (AIH) with detection of non-specific autoantibodies, thus complicating the differential diagnosis. The aim of our study was to identify the specific features for determination of antinuclear factor on the Hep-2 cell line and specific autoantibodies using a triple cell substrate in children with autoimmune hepatitis and WD. We have examined 62 pediatric patients with WD and 28 children with AIH. ANF was determined on the HEp-2 cell line (ANA-HEp-2, AESKUSLIDES®, Germany). Specific auto-antibodies were detected by means of a triple substrate obtained from rodents, which included samples of kidney, liver and stomach tissues (LKS Mouse, Germany) using indirect fluorescence reactions applying an automated analyzer HELIOS® (Germany). The analysis revealed ANF positivity in 15 out of 62 (24%) children with WD. Positive ANF results were obtained in 26 out of 28 children AIH (93%), being significantly more common in AIH compared with WD. The study of specific autoantibodies using a triple substrate revealed positive results in 34 children with WD (55%), versus 26 children with AIH (93%), Hence, the specific auto-antibodies on the triple substrate are more commonly found in children with AIH (p < 0.001) than in children with WD. In children with suspected AIH, when a homogeneous type of luminescence is detected on the HEp-2 cell line, and with a combination of different luminescence types on a triple substrate, the presence of Wilson’s disease in patients cannot be excluded.
版权所有 © Zhuzhula A., Kurbatova O., Petrichuk S., Fisenko A., Snovskaya M., Movsisyan G., Potapov A., Semikina E., 2025 https://creativecommons.org/licenses/by/4.0
Peripheral blood T lymphocytes in burn injury in young children
In our study 31 patients were observed and treated at the burn center of Tyumen city, including 19 boys and 12 girls, aged 1 year to 3 years, with the area of burn wounds of II-IIIAB degree from 7% to 70% of the body surface. Flow cytometry method with monoclonal antibodies CD3, CD4, CD8, CD25 and HLA-DR was used for immunophenotyping of blood lymphocytes. β2-microglobulin (β2-MG) was determined in blood serum using ELISA technique. The venous blood samples conserved with EDTA were taken and analyzed at 24 hours, 7 and 20 days after the injury, thus corresponding to toxic and septic/toxic phase of the disease. Results: There was a statistically significant decrease in the absolute numbers of CD3-positive cells (p < 0.001) and the ratio of CD4/CD8 (p < 0.05) within 24 hours after burn against reference values. The absolute number of CD3+ cells was increased by day 20 of the disease (p < 0.05), yet being under control counts. The number of CD25-expressing T cells did not significantly increase after a burn. Meanwhile, The absolute counts of HLA- DR significantly increase after 20 days (p < 0.001). In addition, there was a significant correlation between the mean values of β2-MG and the levels of CD25 expressing cells (r = 0.58) in the first 24 hours after the injury. Significant negative correlations were found between the average values of β2-MG and the absolute numbers of CD3+ and CD4+ cells after 24 hours and 7 days of illness. The average values of β2-m throughout the duration of the study were significantly higher in patients with burns than in control group, but without significant differences between measurements at 24 hours, 7 or 20 days. The data obtained indicate a constant activation of T cells twenty days after severe burns. Early release of β2-MG is associated with activation of lymphocytes increasing their susceptibility to apoptosis, thus suggesting an altered immune response and a need to support the immune system of patients during first hours after severe burns.
版权所有 © Kostolomova E., Sakharov S., Polyanskih E., Lozovaya P., 2025 https://creativecommons.org/licenses/by/4.0
JAK/STAT signaling: novel prospectives in the obesity diagnostics
The problem of obesity seemed to be nonresolved over the past decades. Obesity has been proven to be an important pathogenetic factor of metabolic disorders in humans, leading to the development of various disorders. Many questions remain open, despite numerous studies, clarifying the aspects of obesity pathogenesis and associated changes in metabolism. The aim of this study was to consider the components of JAK / STAT signaling system: proteins STAT1, STAT3, SOCS1, SOCS3, as well as the level of cytokine IL-6 in blood serum of obese individuals. 210 patients were examined, being divided into groups: I – individuals with normal body weight; II – patients with overweight; III – patients with metabolically healthy obesity, IV – patients with metabolically unhealthy obesity. A set of immunological and general clinical research methods was used in the work. The study revealed significantly altered values of JAK/STAT signaling system components and IL-6 cytokine levels in blood serum of obese patients. Increased serum IL-6 levels were found in obese subjects as well as statistically significant correlation between IL-6 and lipid profile parameters, STAT1, STAT3, and SOCS1, SOCS3 proteins. The STAT1 and STAT3 levels were decreased in obese individuals in contrast to the persons with normal and overweight body weight. An imbalance of SOCS1 and SOCS3 proteins was also observed in individuals with different obesity phenotypes. Significant correlations were revealed between serum IL-6, STAT1, STAT3, SOCS1, and SOCS3 levels, as well as lipid metabolism parameters in patients with metabolic healthy and metabolic unhealthy obesity. The results of these studies are consistent with available literature data on changed expression of STAT1, STAT3 and SOCS1, SOCS3 proteins in obese patients, as well as importance of SOCS1, SOCS3 proteins in STAT expression levels by the negative feedback relations. One may also suggest participation of IL-6 cytokine in activation of JAK/STAT signaling system and maintenance of meta-inflammation in obese individuals. Thus, the study of JAK/STAT signaling indices may be a promising area in diagnostics and search for new strategies in obesity management.
版权所有 © Kulakova A., 2025 https://creativecommons.org/licenses/by/4.0
Reconstructive immunomodulation under the influence of thymic hexapeptide of number and phenotype of subsets CD16+CD62L+CD11b+CD63- and CD16+CD62L+CD11b+CD63+ of neutrophilic granulocytes in children with acute destructive pneumonia, is associated with positive clinical efficacy
Dysfunction of neutrophilic granulocytes (NG) is a decisive factor in the development and progression of atypical purulent-inflammatory diseases, including acute destructive pneumonia (ADP) in children. A promising approach is to include immunocorrective therapy in complex treatment, thus promoting recovery of NG functions. The objective of this study was to assess the features of defective NG functioning associated with changes in relative contents and phenotype of CD16+CD62L+CD11b+CD63- and CD16+CD62L+CD11b+CD63+ neutrophil subsets in children with ADP, to evaluate clinical and immunological effectiveness of immunomodulatory therapy in complex postoperative treatment using a pharmaceutical drug with a synthetic thymic hexapeptide (pdHP) being the active substance. The study included 21 children aged 2-4 years: with a diagnosis of ADP (study group, SG) before complex treatment, and a group after treatment with hexapeptide (SG1). The comparison group included 20 conditionally healthy children (CG), Twenty children treated for ADP comprised the archival comparison group (aCG). The functions of NG were assessed by the content of CD16+CD62L+CD11b+CD63- and CD16+CD62L+CD11b+CD63+ subsets using FC500 (Beckman Coulter) device. We also determined indices characterizing phagocytosis (%PAN, PN, PI, %D, ID), NADPH oxidase activity (%PPC, MCI) in the NBT test. We have found a phenotypic transformation of physiological subset to CD16dimCD62LdimCD11bbrightCD63- NG with defective immune properties, a 3-fold increase in the content of NG subset with hyperactivated phenotype CD16brightCD62LbrightCD11bbrightCD63bright (p < 0.05), a defect in phagocytic function, but increased oxidase activity (p1, 2 < 0.05) in immunocompromised children with ADP. After complex treatment with the inclusion of hexapeptide, we observed normalization of NG effector functions associated with phenotype remodeling and restoration of the subpopulation ratio. Positive clinical dynamics was revealed when compared with aCG children receiving conventional therapy, i.e., a significant reduction in fever duration (|δ| = 0.98), respiratory failure (|δ| = 0.99), more rapid regression of pleural effusion (|δ| = 0.96) and early removal of drainages (|δ| = 1.00). The obtained results indicate a pronounced positive clinical and immunological efficiency of pdHP usage in complex treatment of children with ADP.
版权所有 © Nesterova I., Chudilova G., Safontseva A., Chapurina V., Lyagusha D., Barova N., 2025 https://creativecommons.org/licenses/by/4.0
Changes of peripheral blood parameters in patients with psoriasis
The issues of widespread psoriasis are quite urgent, due to its high prevalence of this disorder, absence of a single etiopathogenetic concept, diversity of clinical forms and systemic nature of the disease manifestations. Metabolic disorders and biochemical defects play an important role in pathogenesis of psoriasis and may be associated with impaired lipid metabolism. High frequency of dyslipidemia and metabolic syndrome in psoriasis determine high risk of cardiovascular diseases. The study of changes in differential leukocyte counts upon general blood testing and biochemical parameters of peripheral blood in psoriasis is of great clinical and diagnostic importance. The purpose of the study was to evaluate basic laboratory parameters of peripheral blood in patients with psoriasis who underwent inpatient treatment at the all-day Department at Chelyabinsk Regional Clinical Dispensary for Dermato-Venereal Diseases. Laboratory parameters of general and biochemical blood tests were studied in 750 patients with psoriasis admitted to the Dispensary. The severity of psoriasis and clinical PASI index were assessed. The counts of red blood cells, leukocytes, platelets, and hemoglobin were determined in blood as well as RBC color index, erythrocyte sedimentation rate (ESR). We have also assessed the levels of glucose, direct bilirubin, total bilirubin, urea, creatinine, C-reactive protein, rheumatoid factor, cholesterol, and triglycerides in blood serum. The study revealed an increased ESR in elderly patients with severe psoriasis. Dyslipidemia with increased level of cholesterol and triglycerides in the peripheral blood was detected in middle-aged and elderly women and men with moderate-degree psoriasis. In patients with psoriasis over 45 years of age with moderate course of the disease, an excess of total bilirubin was more often observed. An increase in systemic inflammation markers, i.e., C-reactive protein, ESR, direct and total bilirubin is observed in psoriatic disease. Lipid metabolism disorders with increased cholesterol and triglyceride levels were more often observed in moderate course of psoriasis among middle-aged and elderly patients.
版权所有 © Nefedyeva Y., Shishkova Y., Ziganshin O., 2025 https://creativecommons.org/licenses/by/4.0
Increased relative CD5+ILC2 counts in patients with rheumatoid arthritis
Innate lymphoid cells (ILCs) are the innate analogues of lymphocytes that do not express antigen-specific receptors and are primarily found in tissues and mucosa. ILCs are divided into three groups based on the transcription factors and cytokines they secrete. Group 1 ILCs produce interferon (IFN)-γ in response to IL-12 and are dependent on the transcription factor T-bet; group 2 ILCs (ILC2s) predominantly produce type 2 cytokines (IL-5, IL-4, IL-9, and IL-13) in response to IL-33, IL-25, and thymic stromal lymphopoietin (TSLP) and are dependent on GATA3. Group 3 ILCs include ILC3s and lymphoid tissue inducer cells (LTi). The latter group secretes IL-17 and IL-22 in response to IL-1β and IL-23 and functionally depends on RORγt. Recently, early ILC precursors were found in peripheral blood, which were defined by the CD5 marker and are likely to be of thymic origin. These cells can, on demand, enter the bloodstream (like monocytes), move with the blood flow into tissues for subsequent differentiation into a mature phenotype. In this work, we assessed the content of CD5+ILC2 in peripheral blood of patients with rheumatoid arthritis (RA), which is characterized by chronic inflammation in the joints and uncontrolled cell proliferation, thus maintaining the inflammatory events. In this work, we used peripheral blood from patients with RA (n = 7) and conditionally healthy donors (n = 13). The obtained peripheral blood mononuclear cells (PBMPs) were stained with the following panel of antibodies: anti-lineage (CD2/3/14/16/19/20/56/235a), antiCD11c and anti-FceR1 alpha-FITC, anti-CD294-PE, anti-CD127-PerCP/Cy5.5, antiCD117-APC, anti-CD5-BV-450. Innate lymphoid cells were defined as Lin-CD127+, CD294+ILCs were identified as ILC2. The proportion of CD5+ cells among ILC2 was also evaluated. The cell phenotype was analyzed by flow cytometry. We showed that the proportion of ILC2 among all PBMPs was significantly lower in patients with RA compared to the donor group, and the number of CD5+ILC2 among ILC2 was significantly higher than in the control group. The obtained results are unique and provide us with new data on the changing percentage of ILC2 among PC MNCs and CD5+ILC2 among ILC2.
版权所有 © Boeva O., Borisevich V., Abbasova V., Kozlov V., Korolev M., Omelchenko V., Kurochkina Y., Rybakova A., Pashkina E., 2025 https://creativecommons.org/licenses/by/4.0
Impact of vitamin D deficiency on efficiency of rehabilitation programs in patients with ankylosing spondylitis
Low blood vitamin D concentrations are associated with incidence, risk of development, activity and more severe clinical course of ankylosing spondylitis (AS). 58 patients with AS (males 62.1%, age 48 (39-58) years) were examined to study the impact of vitamin D deficiency on the efficiency of rehabilitation measures under the programs of sanatorium and resort therapy. Determination (25-OH) of vitamin D level, haematological indices SII (systemic immune-inflammation index; SII = number of platelets × number of neutrophils/number of lymphocytes) and SIRI (systemic inflammation response index; SIRI = number of neutrophils × number of monocytes/number of lymphocytes) were performed on admission to the sanatorium and before discharge. The average BASDAI disease activity index was 3.0 (2.4-3.5) points. Low AS activity was documented in 31% and moderate activity, in 69% of patients. The baseline vitamin D levels showed negative correlation with pain intensity score (VAS, visual analog score) during walking (ρ = -0.44, p < 0.001). Association of these measures at discharge persisted but was less significant (ρ = -0.27, p = 0.039). In the total group of AS patients, vitamin D deficiency (< 20 ng/mL) was observed in 13.8%, and mild deficiency levels (ranging from 20 to 29 ng/mL) have been revealed in 25.9% of cases. When comparing patients with normal (> 30 ng/mL) and reduced (≤ 29 ng/mL) vitamin D levels, significant differences were noted for VAS (p = 0.0025), ESR (p = 0.040) and SIRI (p = 0.046). All patients with AS were divided into two groups: Group I (n = 26) admitted for treatment from regions with low level of solar insolation; Group II (n = 32) arrived for treatment from regions with high insolation levels. Initially, a significantly lower vitamin D content was observed in AS patients in group I (p = 0.040). A three-week stay and treatment at the sanatorium (an area with high solar insolation) was associated with an increase in vitamin D levels (p = 0.027), and decreased VAS pain intensity (p = 0.017) only in group II patients. When testing the inflammatory markers, only SIRI showed a significant decrease in group II patients with AS in the course of treatment (p = 0.038). In conclusion, the hematological SIRI index objectively reflects clinical dynamics of AS patients arriving for sanatorium and resort therapy from the regions with different levels of solar insolation.
版权所有 © Nikitin M., Aleksandrova N., Alekhina I., Bezuglov I., Aleksandrov A., Zborovskaya I., 2025 https://creativecommons.org/licenses/by/4.0
Association of serum angiopoietin-like proteins types 2, 3 and 4 with clinical manifestations of osteoarthritis
Hyperactivity of angiopoietin-like proteins (ANGPTL) involved in persistence of chronic inflammation may lead to progression of different arthropathies. The purpose of the study was to evaluate interrelations between serum angiopoietin-like proteins types 2, 3 and 4 with clinical and laboratory characteristics of osteoarthritis (ОА) and comorbid conditions. We have examined 42 OA patients (females, 78.6%; aged 59.2±8.7 years; mean disease duration of 8.9±5.5 years) More severe joint damage (assessed as radiological stage) was accompanied by an increased levels of ANGPTL type 4 (p = 0.014). The group of OA patients with synovitis had significantly higher rates of type 2 and type 4 ANGPTL than patients without synovitis (p = 0.039 and p = 0.021, respectively). The content of type 4 ANGPTL was also significantly higher in patients with increased values of ESR and C-reactive protein (CRP) (p = 0.018). The associated co-morbidities in OA patients were as follows: obesity (40.5%), arterial hypertension (AH) (38%) and features of metabolic syndrome (MetS) (31%). The levels of type 3 ANGPTL in patients with MetS was higher than in OA patients without MetS (p = 0.024). The levels of type 4 ANGPTL in obese patients was higher than in OA patients with normal body weight (p = 0.027), and the contents of type 3 ANGPTL in this group did not reach the level of statistical significance (p = 0.052). The dispersion analysis also showed a significant effect of obesity degree on the level of type 4 ANGPTL (p = 0.034). The levels of ANGPTL types 2, 3 and 4 did not differ between the groups of OA patients with/without AH (p = 0.11, p = 0.055 and p = 0.09, respectively). However, when comparing patients with different degrees of AH, the difference in ANGPTL type 3 levels reached the level of statistical significance (p = 0.049). In summary, ANGPTLs showed different dependence on the comorbid background in patients with OA: type 2 ANGPTL is associated with inflammatory processes in joints; type 3 ANGPTL correlates with presence of MetS and severity of AH. Type 4 ANGPTL is associated with obesity, inflammation and severity of joint damage.
版权所有 © Aleksandrov V., Shilova L., Aleksandrov A., 2025 https://creativecommons.org/licenses/by/4.0
Evaluation of СХС chemokine levels in cerebrospinal fluid of patients with brain contusions
Traumatic brain injury (TBI) is among the most common forms of neurological pathology. In traumatic brain injury, axonal damage occurs not only as a result of direct cytotoxic interactions, but also due to activation of pro-inflammatory cytokines and chemokines, which play a crucial role in development and maintenance of neuroinflammation. At the early terms after brain trauma, there occurs both activation of microglia, and formation of a pool of T cell subsets able to produce various chemokines. The aim of this study was to assess the contents of chemokines (CXCL8/MIG, CXCL9/IP-10, CXCL10/I-TAC) in cerebrospinal fluid (CSF) of patients with brain contusion of varying severity within the first 24 hours after hospital admission. The study included 86 patients diagnosed with “TBI: brain contusion,” who were divided into three groups based on the injury severity. A comparison group consisted of patients with brain concussion (n = 24). Obtaining CSF from healthy individuals is challenging due to absence of clinical indications for lumbar puncture. Chemokine concentrations (pg/mL) were measured by means of multiplex analysis based on xMAP technology (Luminex, USA), using Milliplex MAP test systems (Millipore, USA). The results showed a trend toward increased chemokine levels correlating with more pronounces severity of brain injury. Notably, CXCL9/MIG levels were elevated in all patients with brain injury (p < 0.05), unlike CXCL8/IL-8, which showed significant increases only in the 4th group (severe TBI), and CXCL10/IP-10, which was significantly elevated in both the 3rd (moderate TBI) and 4th groups. Specifically, in the 4th group (severe TBI), levels of CXCL8/IL-8 were increased 3.5 times, CXCL9/MIG showed a 9-fold increase, and CXCL10/IP-10 was 3 times higher than in control group (1st group, mild TBI). To evaluate the diagnostic value of these changes, ROC analysis was performed, establishing a clinically significant chemokine thresholds that serve as highly informative markers of neural tissue damage. In conclusion, assessment of CXCL8, CXCL9, and CXCL10 levels in CSF following brain contusion provides valuable insights into their role in disease progression, i.e., recruiting T helper cells and neutrophils from peripheral blood into neural tissue and sustaining neuroinflammatory processes.
版权所有 © Norka A., Vorobyev S., Kuznetsova R., Korobova Z., Totolian A., 2025 https://creativecommons.org/licenses/by/4.0
Immunological memory to SARS-CoV-2 S protein persists 4 years after the disease
Ending of COVID-19 pandemic does not exclude subsequent breakthrough infections caused by SARS-CoV-2 mutant strains. The rate of SARS-CoV-2 mutations increased with emerging omicron strain and exceeds those of the influenza virus. It remains unclear what IgG antibody levels are able to protect against new mutant SARS-CoV-2 strains, and how long the immune protection will last. The objective of this study was to monitor the maintenance of humoral and cellular immunity to SARS-CoV-2 viral antigens over 4 years after the infection. Thirty-two adult reconvalescents after COVID-19 were annually examined for humoral and cellular immunity markers to the SARS-CoV-2 S protein. Humoral immunity was assessed by ELISA; cellular immunity was evaluated by expression of CD107a on CD8hi lymphocytes after recognition of S protein antigens. A four-year observation of a group of patients who recovered from COVID-19 in 2020 (SARS-CoV-2, Wuhan strain) and were in contact with a novel, freely circulating mutant VoCs showed that, 1 year later, all subjects retained the IgG antibodies to S protein, mainly the IgG1 subclass, but the antibody avidity index barely exceeded 50%. After a breakthrough infection caused by the omicron strain, the level of IgG antibodies to S protein increased significantly, along with sufficient increase of antibody avidity. The IgG2, IgG3, and IgG4 antibodies to S protein occured in the spectrum of subclasses. The level of specific IgA decreased 1 year after the disease against their level after the primary disease. However, it was significantly increased to 4-5 PR after breakthrough infections. Cellular immunity to the SARS-CoV-2 S protein was detected in all subjects at 1 year after the primary disease. After repeated infection with the omicron strain, it increased significantly and remained at this level for the next year. By 4 years, it decreased to the level that was a year after the disease. Hence, humoral and cellular immunity to S protein does not fade away, but continues to persist, maturate, being maintained at a sufficient level. Upon exposure to a new VoC, it allows to endure such a meeting either asymptomatically, or as a mild clinical infection. In view of frequent mutations in the S protein, the role of T-cell responses in anti-infectious protection seems to increase significantly. When developing new vaccines, one should rely on development of cellular immunity.
版权所有 © Afridonova Z., Toptygina A., Semikina E., 2025 https://creativecommons.org/licenses/by/4.0
Influence of clinical features in acute COVID-19 infection on the course of post-COVID syndrome
The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in global morbidity and high mortality rates worldwide. According to case histories, for a long time after acute COVID-19 infection (six months to 2-3 years), patients may experience a pronounced fatigue, increased tiredness, higher incidence of acute respiratory viral infections per year, increased recurrence of skin diseases, allergies, exacerbation of pulmonary disorders, urinary tract diseases, increased recurrence of chronic viral diseases, e.g., herpesvirus and papillomavirus infections, aggravation of chronic cardiovascular and other somatic diseases of various organs and systems. Patients were examined at early as six months after recovery from acute COVID-19. Such persistent post-infectious consequences are referred to as post-COVID syndrome. When assessing post-COVID syndrome, it is necessary to identify the main clinical syndromes of multiorgan pathology characteristic of post-COVID patients. Endocrine and cardiac manifestations of post-COVID syndrome may be a consequence of direct damage from viral infection, immunological and inflammatory damage, as well as iatrogenic complications. Objective of our study was to assess the impact of acute COVID-19 severity on the course of post-COVID syndrome. The research objectives were as follows: 1. To analyze the severity of clinical manifestations of cardiovascular disorders in post-COVID patients depending on the degree of lung damage in the acute period of COVID-19 (CT0 to CT4). 2. To analyze the severity of clinical manifestations of endocrine disorders, including newly diagnosed pathology, in post-COVID patients depending on the degree of lung damage in acute period of COVID-19. Since we did not found any significant gender-and age-dependent differences, all patients were divided into groups by the degree of lung damage during acute period of COVID-19, according to clinical guidelines for the diagnosis and treatment of a new coronavirus infection. This study showed that the clinical picture of post-COVID syndrome is characterized by a pronounced diversity in development of multiple organ pathology, both newly diagnosed, or manifesting by increased frequency of exacerbations of chronic diseases. Conclusions: 1. According to the data obtained, reliable differences were obtained between groups CT0 and CT1-2, as well as CT0 and CT3-4: the frequency of exacerbating cardiovascular disorders in the post-COVID period is significantly higher in groups with lung damage over acute period of COVID-19 compared to the group of patients without lung damage. These data suggest that cardiovascular disorders are directly related to the severity of COVID-19, viral load, and were detected most frequently (68%) in post-COVID patients who initially had a severe coronavirus infection. 2. According to our results, the frequency of glucose metabolism disorders, including those detected for the first time, proved to be significantly increased in the post-COVID patients with lung damage during acute infection. Meanwhile, no significant differences were found for thyroid disorders, except of autoimmune thyroiditis (AIT). These disorders may be associated with usage of corticosteroid therapy in acute period of coronavirus infection, or with impairment of regulatory mechanisms of the endocrine and immune systems induced by SARS-CoV-2 virus, thus again confirming our assumptions concerning development of multiple organ pathology in post-COVID patients.
版权所有 © Dobrynina M., Zurochka V., Zurochka A., 2025 https://creativecommons.org/licenses/by/4.0
Сomparative immune resistance of Enterococci and Staphylococci isolated in chronic bacterial prostatitis
The aim of the study was to conduct a comparative analysis of immunoresistance factors in enterococci and staphylococci strains isolated in chronic bacterial prostatitis (CBP). In vitro studies were conducted on 24 clinical strains of Gram-positive cocci of different species: Enterococcus faecalis (n = 6), Staphylococcus aureus (n = 6), coagulase-negative staphylococci (CoNS): S. haemolyticus (n = 6), S. epidermidis (n = 6), isolated from prostatic secretion in men with CBP. Antilysozyme activity (ALA) of bacteria and their ability to form biofilms (BFA) were determined photometrically; sIgA protease activity of bacteria and their anticytokine activity (ACA) in relation to pro- and anti-inflammatory cytokines (IL-6, IL-8, IL-17A, TNFα and IL-4) were determined by the enzyme immunoassay. The obtained data were processed by the methods of variation statistics and the Spearman correlation criterion. Upon the comparative analysis of immunoresistance factors in enterococci and staphylococci isolated in CBP, no significant differences in the expression levels of ALA, BPO, and ACA in relation to IL-8 and TNFα were revealed between the isolates of bacteria of the studied species, but their interspecies variability in sIgA protease expression and ACA against IL-4, IL-6, and IL-17A were noted. The results of correlation analysis have shown a close positive relationship between the expression of ACA IL-8 and ACA IL-6 in CoNS and S. aureus isolates, as well as between sIgA protease activity and ACA IL-6 in CoNS and E. faecalis strains. Inverse correlations were found between ACA to IL-8 and ACA to IL-17A, ACA IL-8 and BFA. Moreover, BFA and ACA to TNFα were detected in E. faecalis. These results allowed us to characterize a number of immunoresistance factors associated with inactivation/suppression of antimicrobial defense mechanisms in clinical strains of E. faecalis, S. aureus and CoNS of different species isolated from patients with CBP, which may contribute to the survival and long-term persistence of pathogens in the prostate gland. Further studies in this area can provide new practically useful data, including information related to the prediction of persistence for distinct bacterial strains.
版权所有 © Pashinina O., Pashkova T., Kartashova O., Popova L., Kuzmin M., Gritsenko V., 2025 https://creativecommons.org/licenses/by/4.0
Systemic relationships of inflammatory, hormonal, and metabolic markers in women with polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders observed in women of reproductive age and is characterized by a wide range of clinical manifestations, including ovulatory dysfunction, hyperandrogenism, and metabolic alterations, such as insulin resistance and obesity. In recent years, increasing attention has been given to immune factors and systemic inflammation in pathogenesis of this syndrome. Our objective was to determine the levels of anti-Müllerian hormone, gonadotropins, proinflammatory cytokines, carbohydrate metabolism parameters, and insulin resistance index in women with different clinical phenotypes of PCOS depending on the type of menstrual cycle. The study included 86 women at their reproductive age, being divided into four groups: a control group (women without menstrual cycle disturbances) and three groups of patients with PCOS, stratified by the type of menstrual irregularity: regular cycle, oligomenorrhea, and amenorrhea. All participants underwent evaluation of serum levels of anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone, glucose, insulin, and proinflammatory cytokines including IL-6, TNFα, and IL-17A. Insulin resistance index was also calculated in accordance with a homeostatic model. The findings demonstrated significantly increased levels of all evaluated hormonal and immune parameters in women with PCOS compared to the control group, with the most pronounced changes observed in amenorrheic subgroup. The results of the study confirm a systemic interrelationship between inflammatory, hormonal, and metabolic disturbances in women with PCOS. Proinflammatory cytokines may serve as potential biomarkers of disease severity, and their comprehensive assessment, along with hormonal and metabolic markers may enhance the accuracy of diagnosis and support a more individualized approach to therapy in this patient population.
版权所有 © Azizova Z., Musakhodzhayeva D., Ruzimurodov N., Olimova N., 2025 https://creativecommons.org/licenses/by/4.0
Characteristics of the chemokine profile in women with adenomyosis
Adenomyosis is a chronic inflammatory disease characterized by the infiltration of endometrial tissue into the myometrium and the activation of immune-inflammatory responses at both local and systemic levels. A key aspect of the disease’s pathogenesis involves alterations in the regulation of cytokine and chemokine balance, disturbances in angiogenesis, and processes of uterine wall remodeling. All these factors contribute to disease progression and worsening of patients’ conditions. Recent studies increasingly emphasize the role of the immune system, particularly chemokines, in the development of adenomyosis, as well as the potential use of immunological markers for diagnosis and monitoring of disease progression. The aim of the present study was to analyze the chemokine profile in women with stage I-II adenomyosis. Concentrations of the following chemokines in blood plasma were studied: IL-8, MCP-1, IP-10, and MIP-1β. The study included 81 women of reproductive age residing in the city of Urgench, Khorezm region, of whom 56 patients were diagnosed with adenomyosis (stage I or II), and 25 healthy women served as the control group. Enzyme-linked immunosorbent assay (ELISA) was used to determine chemokine concentrations, and Student’s t-test was employed for statistical analysis. The results revealed significant changes in the chemokine profile in patients with adenomyosis. Levels of IL-8, MCP-1, and MIP-1β were significantly elevated (by 3.7-, 1.9-, and 1.6-fold, respectively), indicating the development of an inflammatory process and activation of various components of the immune response. Elevated IL-8 levels were associated with angiogenesis and neutrophil infiltration of tissues, MCP-1 with the recruitment of monocytes and macrophages to the inflammatory site, and MIP-1β with activation of innate immunity. Meanwhile, IP-10 levels showed a tendency to decrease (~12%), which may indicate a reduction in anti-angiogenic activity and disruption of the Th1 response. Thus, the study confirmed a pronounced imbalance of chemokines in adenomyosis and highlighted promising directions for the diagnosis and monitoring of this disease. Investigating immune mechanisms may be valuable for developing new therapeutic approaches based on correcting the identified abnormalities.
版权所有 © Musakhodzhayeva D., Rustamova N., Azizova Z., Mannopzhonov P., Ismailova D., 2025 https://creativecommons.org/licenses/by/4.0
Evaluation of the impact of genetically engineered biological therapy on HLA-E expression in bronchial asthma and atopic dermatitis
Globally, the prevalence of bronchial asthma (BA) alone reaches 19%, with the number of affected individuals showing an upward trend. Atopic dermatitis (AD) affects 25-30% of children and 7-10% of adults. Remission remains elusive even with advanced genetically engineered biological therapies. Consequently, research into immunopathogenic pathways and the development of novel therapeutic strategies remain critical. A typical representative of “non-classical” HLAs, the HLA-E molecule, is a perspective for study. These molecules are also expressed across various tissues, notably in the respiratory system (bronchial epithelium) and skin keratinocytes. As a cell surface protein, HLA-E participates in diverse immune response pathways. VL9 peptides stabilize HLA-E expression, enabling presentation to its primary receptors, NKG2, on natural killer (NK) cells. In adaptive immunity, HLA-E serves as a ligand for CD8+ cytotoxic T cell receptors (TCRs). This study aimed to evaluate HLA-E-bearing cells (CD4+, CD8+, CD14+) in patients with BA and AD, both before and 12 months after initiating genetically engineered biological therapy (GEBT). Peripheral blood mononuclear cells (PBMCs) were analyzed from healthy donors (n = 16), BA patients (n = 4), and AD patients (n = 5). AD patients received dupilumab (300 mg loading dose), while BA patients were treated with benralizumab (30 mg). Prior to therapy, both AD and BA patients exhibited lower proportions of HLA-E-positive CD4+ and CD8+T cells compared to healthy donors. No significant differences were observed in HLA-E expression on CD14+ monocytes. During treatment, HLA-E levels across all cell types in patients reached levels comparable to those in healthy donors. These findings suggest HLA-E’s involvement in disease pathogenesis and the modulating effects of GEBT on HLA-E-positive cell populations.
版权所有 © Borisevich V., Boeva O., Abbasova V., Demina D., Kozlov V., 2025 https://creativecommons.org/licenses/by/4.0
Combined immunodeficiency in elderly persons with COPD as a manifestation of immune aging
The study of immune system (IS) functions in chronic respiratory pathology is especially relevant in elderly and senile persons, since frequent prolonged exacerbations of chronic obstructive pulmonary disease (COPD) significantly affect the condition of patients, leading to decompensation of diseases. The objective of this study was to perform expanded evaluation of IS state, and to specify the variants of disorders in elderly and senile patients with COPD. 10 patients aged 60-80 years with COPD comprised the study group (SG) l; the comparison group (CG) included 30 conditionally healthy individuals. The general and local clinical status was determined. Before treatment, the following immune parameters were studied: T lymphocytes (CD3+CD19-, CD3+CD4+, CD3+CD8+), B lymphocytes (CD3-CD19+), NK cells (CD3-CD16+CD56+), two subsets of neutrophilic granulocytes (NG) CD64-CD32+CD16+CD11b+ and CD64+CD32+CD16+CD11b+ using an FC-500 Beckman Coulter device, with calculation of the CING index reflecting the ratio between the two NG subpopulations. Phagocytic function of NG was evaluated, i.e., engulfment (%PAN, PN, PI), killing and digestion (%D, ID) of microbial particles (S. aureus, strain 209), as well as NADPH oxidase activity by the NBT test. The SG patients showed combined immunodeficiency of varying severity: quantitative deficiency of T lymphocytes due to a decrease of T helper cells (p < 0.05), altered effector function of NG (deficiency of actively phagocyting NG, impaired capture, digestion and killing, p1-3 < 0.05). A decrease in the CD64-CD32+CD16+CD11b+NG subset, and an 8.9-fold increase in “immature” subset (negatively transformed CD64+CD32+CD16+CD11b+) were shown, suggesting an inferior NG response to bacterial infection. When calculating the CING, bacterial infections were detected: Mild, moderate and severe conditions were diagnosed, respectively, in 60%, 10% and 30% of SG patients. The evidence of immunodeficiency in elderly and senile COPD patients has been obtained, thus requiring development of immunotherapeutic approaches aimed at recovery of IS defects, in order to increase the efficiency of COPD therapy and improve the quality of life in patients.
版权所有 © Pirogova A., Lomtatidze L., Filippov E., 2025 https://creativecommons.org/licenses/by/4.0
Current views of medical professionals on fever may cause a fever phobia
Fever is an extremely common symptom in children and the most common reason for visiting a pediatrician. There are many studies worldwide indicating that physicians and parents have a lot of misconcepts and conflicting results regarding fever. This is due to the methodological limitations of available studies in the field of fever, some disagreements in terminology, orientation towards patient comfort when making treatment decisions and lack of a holistic approach to the body reactivity. In this study, we sought to identify the knowledge, attitudes and misconcepts of primary care physicians regarding fever in children. This cross-sectional study was conducted in June-July 2024 with the participation of physicians and nurses at pediatric clinics (n = 209). Physicians, with verbal consent, independently completed the proposed questionnaire. In the study, a third of respondents had conflicting answers, whether a fever state should be considered a normal or pathological response in health disorder. All pediatricians recommend to bring the temperature down, and only 13.4% preferred to do it, if the child feels unwell. The overwhelming majority believes that fighting fever is not harmful to the body, although 72.2% note that administration of antipyretics may mask more serious problems. It is positive that 58.8% of doctors suggest bringing down the fever at > 39-39.5 °C, as currently recommended. A fewer number of respondents (13.9%) associate fever with a bacterial infection. There are misconcepts among health workers regarding fever after vaccination, during teething, the needs for physical cooling measures, mandatory watering, and indications for seeking medical care. All health workers have fears regarding the consequences of pyrexia, especially regarding convulsions, loss of consciousness, protein denaturation, and dehydration. On the one hand, this attitude demonstrates alertness and encourages a diagnostic search. On the other hand, it increases fear of fever. As a result, the instructions and definitions given to parents regarding fever treatment are often contradictory and incomplete. Most health care providers recognize the lack of knowledge in this area. By focusing on fever treatment, we suggest an impression for parents that fever is harmful and antipyretics are beneficial. Are there long-term consequences of such a daily struggle when the primary goal is to maintain health?
版权所有 © Naydеnkina S., Ermakova M., Motigullin R., 2025 https://creativecommons.org/licenses/by/4.0