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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To the issue of neuro-immuno-endocrine system theory
The review presents the history of evolving views about interrelations between the immune, nervous, and endocrine systems, A number of arguments justify the concept suggesting that they are components of a single regulatory system, since their structures are tightly integrated into each other, and they use similar biologically active substances as signaling molecules. At the same time, distinct molecules, depending on the cell of origin, may be classified as neurotransmitters, hormones, or cytokines. Receptors for cytokines were found on peripheral neurons and vagal nerve endings, e.g., IL-4 regulates synaptic transmission. The ability of immune cells to produce hormones and neuropeptides has been recently proven. Catecholamines may originate from the cells of immune system. Hypothalamic neurosecretory cells express IL-1, and astrocytic glial cells may express interferon. They always act together, in functional regulation by complementing or replacing each other, having a common coordination center. E.g., the anterior lobe of pituitary gland, by secreting growth hormone, may affect synthesis and secretion of thymulin by epithelial thymic cells. Thus, the hypothalamic-pituitary-thymic axis is formed. On this basis, neuroimmunoendocrinology, a new scientific discipline, has emerged. The disorder of a distinct subsystem leads to significant changes in its other compartments. There is not a single type of pathology that would not involve all three components of the whole system. The unity of all components of the system is most clearly observed in stress, traumatic shock, and cytokine storm. Cross-usage of drugs for the therapy of diseases affecting either of the three systems is of particular interest. For example, usage of immunotropic drugs has found applications in the treatment of psychiatric disorders. Pharmacological effects on macrophages are currently implemented in the treatment of endocrine disorders. Thus, sufficient evidence has been accumulated to consider the immune, nervous and endocrine systems an integrated system of physiological regulation which is presumably based on transmission and processing of information.
Copyright (c) 2026 Chereshnev V.A., Yushkov B.G. https://creativecommons.org/licenses/by/4.0
Comparative characteristics of different endotypes in chronic rhinosinusitis
Chronic rhinosinusitis (CRS) is the most common reason for consulting at the otolaryngologist. Although data on the prevalence of rhinosinusitis are inconsistent, the average global prevalence was 11.61±5.47%, ranging from 1.01% to a maximum of 57.6%. As based on the consensus document EPOS 2020 (European Position Paper on Rhinosinusitis and Nasal Polyposis), CRS is classified into polypous and polyp-free rhinosinusitis. Polypous rhinosinusitis is a special type characterized by inferior response to conservative therapy, and frequent relapses after surgical treatment. These serious medical and social issues are promoting the studies on pathogenesis and development of nasal polyps. This review provides information about immunological features and dysfunction leading to emergence of CRS with or without polyps. The purpose of this literature review is to evaluate the role of the first-line immune defense, congenital and acquired components of immunity in pathogenesis of polyposis versus nonpolypous CRS. The article provides a review of the research articles published worldwide. The authors conducted a search on the significance of immune response in development of CRS with and without polyps. We used appropriate keywords and filters in the PubMed and Google Scholar databases, in Scopus, Web of Science, MedLine, Cochrane Library, EMBASE, Global Health, and CyberLeninka databases. The detailed search has shown that all components of immune system do not fully perform their functions. E.g., the respiratory epithelium and mucociliary clearance present the first-line immune defense of nasal and sinus mucosa which form a mechanical barrier to infectious and other invading agents. At the next stage, the cells of innate immune response, along with complement system, take part in elimination of external pathogenic agents. Presentation of antigen epitopes to lymphocytes generates a specialized adaptive immune response. Tissue remodeling is among the most relevant aspects of the CRS pathogenesis. Production of periostin is found to be increased in polyposis rhinosinusitis, along with progressive tissue eosinophilia, higher production of cystatin SN, IL-25 and fibroblast contents, decreased TLR2, TLR4, TGF-β and collagen production as well as increased extracellular neutrophil traps and M1 macrophage levels. Further studies on the links in immune pathogenesis of CRS could allow us to develop a personalized algorithm for the diagnosis and treatment of such patients.
Copyright (c) 2026 Lazareva A.M., Smirnova O.V. https://creativecommons.org/licenses/by/4.0
Schnitzler’s syndrome, an underdiagnosed autoinflammatory disease: current and future perspective
Schnitzler’s syndrome is a rare but usually underdiagnosed autoinflammatory disease, characterized by monoclonal IgM gammopathy, persistent urticaria, intermittent fever, bone pain, and arthralgia or arthritis. Although first reported by Dr. Liliane Schnitzler in 1972, the syndrome continues to pose challenges in diagnosis, and it usually takes more than five years before it is properly identified. Disorders show up in a form of urticaria, arthritis, organomegaly, fever, lymphadenopathy, high ESR, leukocytosis, and bone pain. Central to its pathogenesis are immunologic perturbations and activation of the inflammasome. It is typically diagnosed through clinical exam with history and important feature identification such as monoclonal gammopathy and acute or relapsing urticarial rash. Therapeutically synthetic agents include anakinra, canakinumab, rilonacept, and anti-IL-6 have been used with variable success. Recent research also demonstrated how natural treatments such as Terminalia chebula, Emblica offcinalis, Schinus terebinthifolia, tulsi, asafoetida, and Wedelia plants have the potential for controlling the symptoms and changing inflammatory paths. Promising medicinal possibilities for these plants, according to in silico investigations, point to further research into their clinical uses. With new therapy paths that promise better patient outcomes, Schnitzler’s illness is overall a therapeutic challenge.
Copyright (c) 2026 Jakhar M., Rani N., Singh R., Singh T. https://creativecommons.org/licenses/by/4.0
Physical exercise is the best therapy in reducing interleukin-6 levels as an inflammatory mediator: a systematic review
Unhealthy lifestyles such as consuming less nutritious foods, lack of physical activity trigger accelerated aging. Aging occurs due to inflammatory processes in the body associated with increased levels of interleukin-6 (IL-6). IL-6 is a major pro-inflammatory cytokine involved in pathogenesis of various chronic diseases, including cardiovascular disorders, diabetes, and autoimmune conditions. Increased levels of IL-6 are associated with systemic inflammation and poor health outcomes. In recent decades, physical exercise has received attention not only for its role in improving fitness but also as a non-pharmacological intervention to modulate the immune response. Currently, there are scarce data on effects of exercise on the IL-6 response. The underlying mechanisms are also still not clearly understood. The physiological response of exercise to IL-6 is important to know and the underlying molecular mechanisms must be clearly understood in order to understand the stages related to the effect of exercise on increasing IL-6. The objective of this study was to determine the mechanism by which physical activity lowers IL-6 levels. In this systematic review, we searched through literature databases including Science Direct, Web of Science, MEDLINE-Pubmed, and Scopus. Our inclusion criteria covered the papers published over the past five years that addressed IL-6 and physical exercise. The Web of Science, Pubmed, and Science Direct databases were used to locate a total of 126 published papers. For this systematic review, ten papers that met the inclusion criteria were selected and examined. Standard operating procedures were evaluated in this study using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Based on the results of this systematic study, it is evident that chronic exercise reduces IL-6 levels. Immediately after acute physical exercise, IL-6 levels are increased. However, there was a downward trend in IL-6 levels during chronic physical exercise. Chronic and regular exercise has been shown to reduce IL-6 levels. as a marker of inflammation. If IL-6 levels may be suppressed through exercise, inflammation will decrease, thus preventing aging which is triggered by the accumulation of inflammatory factors.
Copyright (c) 2026 Ayubi N., Wibawa J., Lobo J., Komaini A., Callixte C., Rizki A., Afandi A., Sabillah M. https://creativecommons.org/licenses/by/4.0
Comparison of cytochemistry and flow cytometry for leukemia immunophenotyping: a systematic review and meta-analysis
Accurate diagnosis and classification of leukemia are essential for effective treatment planning. Traditional cytochemistry relies on enzyme-based staining for morphological evaluation, while flow cytometry (FCM) employs monoclonal antibodies to detect multiple surface and intracellular markers. This systematic review and meta-analysis compared the diagnostic accuracy of cytochemistry and FCM in leukemia immunophenotyping. A systematic search of PubMed and Google Scholar was conducted according to PRISMA guidelines. Studies evaluating sensitivity, specificity, and accuracy of cytochemistry and FCM in diagnosing acute and chronic leukemia were included. Data extraction covered study characteristics, diagnostic markers, and performance outcomes. Meta-analysis was performed to compare diagnostic values across methods. Eleven eligible studies comprising pediatric and adult leukemia cases were analyzed. Cytochemical stains such as myeloperoxidase (MPO) and sudan black B showed high specificity (91-100%) and moderate-to-high sensitivity (60-97%), while periodic acid–Schiff (PAS) and nonspecific esterase had lower reliability. FCM demonstrated superior diagnostic performance with average sensitivity of 87.7% and specificity of 85.6%, achieving > 95% accuracy in several studies. Marker panels including CD3, CD45, CD79a, and MPO enabled precise subtype differentiation and minimal residual disease detection. Cytochemistry remains useful as an affordable screening tool in resource-limited settings, but FCM provides greater sensitivity, specificity, and comprehensive immunophenotypic data, making it the preferred method for leukemia diagnosis and monitoring. Combining both approaches can enhance diagnostic performance across diverse clinical contexts.
Copyright (c) 2026 Kumar A., Matreja P., Singh V., Awasthi S. https://creativecommons.org/licenses/by/4.0
IL-10 and IL-17 contents in culture supernatants of γδ T lymphocytes expanded from blood of patients with reactive erythema
Reactive erythemas represent a group of dermatoses with complex immunogenesis, in which γδ T cell subpopulations may be involved, like as in development of many autoinflammatory diseases. Despite an important role of IL-17, its excessive synthesis, e.g., by γδT cells, is able of inducing autoinflammation. On the contrary, IL-10 plays a key role in the control of innate immune responses. It may suppress functions of monocytes/macrophages by reducing pro-inflammatory cytokine production. Our aim was to perform in vitro expansion of γδ T cells by culturing lymphocytes from peripheral blood of patients with erythema. Peripheral blood mononuclear cells (PBMC) were isolated from 8 patients with reactive erythema (5 patients with erythema multiforme, 1 patient with ring–shaped centrifugal erythema, 2 patients with erythema migrans, an early form of Lyme disease), and two healthy donors aged 23 to 70 years. A modified van Acker et al. method (2016) was used to culture γδ T lymphocytes. The blood cell cultures were supplied with zoledronate, IL-2 and IL-15. The contents of IL-17 and IL-10 were determined in cell culture supernatants by solid-phase ELISA using Human IL-17 ELISA Kit (RK00397, ABclonal Biotechnology Co., China) and Interleukin- 10-ELISA-BEST (JSC "Vector-Best", Russia) according to the manufacturers’ instructions. In patients with reactive erythema, 3.1% to 62.8% of cells with expression of γδ TCR were obtained by 7 days of cultivation with zoledronate, IL-2 and IL-15. The lowest percentage of these cells was observed in blood cell culture from patients with continuously recurrent erythema multiforme and ring-shaped centrifugal erythema. In the group of patients, high levels of induced IL-17 production may indicate a presence of an autoimmune component in pathogenesis of the disease and/or reflect the severity of its course. The effectiveness of therapy in the examined patients correlated with ability of cultured blood cells to synthesize and release IL-10. It has been shown that high values of spontaneous and induced IL-10 production are associated with a good response to therapy (significant clinical improvement, long-term clinical remission). Meanwhile, low values of spontaneous and induced IL-10 production were detected in patients with weak therapeutic effect (rapid development of relapses following the course of therapy). The data obtained suggest a probable prognostic significance of these substances as clinical biomarkers. The determination of these cytokines in blood cell cultures in patients with the studied pathologies may improve the assessment of therapeutic efficiency and predict the course of the disease. However, further research is needed in this area, including other types of clinical disorders.
Copyright (c) 2026 Sorokina E.V., Kalinichenko E.O., Bisheva I.V., Stolpnikova V.N., Skhodova S.A. https://creativecommons.org/licenses/by/4.0
In vitro immunomodulatory effect of Opisthorchis felineus hemozoin on dendritic cells of children with bronchial asthma
Predominance of the Th2 pathway was noted for adaptive immune response in atopic diseases. The Th2-type response is characterized by increased levels of IL-4, IL-5, IL-13, triggering humoral and cell-mediated immune responses associated with production of IgE, basophils, eosinophils and mast cells. Current research focuses on immunoregulatory potential of helminths and their excretory products, which have potential for the pharmaceutical industry. It is known that the parasite in host organism is able to evade the immune response and it may inhibit, alter and modify the current immune responses in the host by producing immunomodulatory substances. The excretory/secretory products resulting from the co-evolution of the host and parasite, may suppress the type 2 immune response, while activating type 1 and type 17 responses. The immunosuppressive microenvironment created by helminths may not only help them to evade the host immune response, but also prevent serious damage to the body caused by excessive inflammation. The role of liver fluke in reducing inflammation has been shown in allergic diseases. The excretory/secretory molecule of the liver fluke (hemozoin) is a promising product of parasitic origin which has a pronounced immunomodulatory properties: it is a dark brown insoluble biocrystal substance synthesized during the life of hematophagous parasites Rhodnius prolixus, Schistosoma mansoni, Plasmodium falciparum, Echinostoma trivolvis, Haemoproteus columbae, Clonorchis sinensisi and Plasmodium falciparum, Opisthorchis felineus. In this regard, the search for helminth-associated molecules exhibiting immunomodulatory effects with low toxicity and immunogenicity, seems to be an urgent task. The aim of the present study was to establish the effect of O. felineus hemozoin on the cytokine profile of dendritic cells (DCs) in patients with bronchial asthma. It was shown that a combined stimulation of DCs from examined patients with the D. pteronyssinus antigen and O. felineus hemozoin is associated with high levels of Th1 profile cytokines (IL-1β, IFNγ), as well as high activity of Treg cells (IL-10). Hence, the liver fluke hemozoin is able to change the cytokine profile of DCs in patients with bronchial asthma. This property of native hemozoin isolated from O. felineus may be further studied for correction of disorders associated with Th2 polarization of immune response which is a common feature of atopic diseases.
Copyright (c) 2026 Melenteva A.P., Podporina M.A., Ogorodova L.M., Fedorova O.S. https://creativecommons.org/licenses/by/4.0
Features of allergic status in a patient with T341P desminopathy
Desminopathies are considered rare or so-called “orphan” diseases. Therefore, little is known about sensitivity of these patients to allergens and physical factors. The aim of our report was to investigate the allergic status of a patient with desminopathy carrying T341P mutation in a heterozygous state. The retrospective study is based on a case of familial desminopathy identified in South-Western Siberia. Quantitative analysis of total and specific immunoglobulins in blood and coprofiltrate of a proband with desminopathy was carried out by means of turbidimetric and chemiluminescence immunoassay, enzyme allergosorbent testing, and ELISA technique. The proband with desminopathy was diagnosed with polyvalent allergy to plant-, food- and infectious allergens. Specific IgE antibodies to pollen of early-blooming meadow grasses and Secale cereale, as well as to cow’s milk, Mucor racemosus and Fusarium moniliforme fungi were found in the blood. Coprofiltrate from the patient revealed specific IgE to pollen of early-blooming meadow grasses and trees, as well as to chicken eggs and casein. Whereas total serum IgE level at the onset of clinical desminopathy symptoms showed two-fold increase over the reference values, it was decreased by 5.5 times over the past 10 years. Over the last two years, the total concentration and average level of specific IgG4 antibodies to food allergens in blood increased by 15%. Provocation tests for cold- and cholinergic urticaria were positive. A respiratory allergy, which emerged by the age of 20 could be the probable trigger of clinical events in desminopathy with T341P mutation. Just by this age, the proband developed ventricular extrasystolia, as well as a barely felt decrease in physical strength. Then, since the age of 30, there was a progressive weakness of the skeletal muscles and a noticeable decrease in physical strength, followed by whole-scale development of the disease, which became severe after 40 years old. Being combined with excessive colonization of intestinal and oral microbiota, and increased endotoxin levels, the polyvalent allergies with high concentration of specific IgG4 antibodies and other (sub)classes may participate in pathogenesis of T341P desminopathy.
Copyright (c) 2026 Pauls V.Y. https://creativecommons.org/licenses/by/4.0
Sensitization pattern and IgE cross-reactivity to peanut allergen molecules in patients with allergic diseases
Peanuts are widely used to produce multi-component food products. Such meal may cause severe allergies in patients with sensitization to peanuts. The severity of symptoms depends on both individual characteristics of immune system and on distinct peanut allergen components causing the hypersensitivity. In addition, peanut contains protein components similar in structure and function to molecules of other plant species, thus leading to occurence of cross-allergic reactions. The aim of our study was to detect sensitization to peanut allergen components and evaluate their IgE cross-reactions with homologous proteins of other superfamilies in patients with allergic diseases. A total of 29 serum samples from patients with atopic diseases were tested. In these sera, sIgEs to 112 allergen components were determined using ImmunoCap ISAC panel (Phadia, Sweden). The detection frequency of sIgE to rAra h 8 was maximal (55.17%; 16 patients of 29), while the level of these antibodies was 0.92±0.39 ISU-E. The level of sIgE to rAra h 2, nAra h 6 and rAra h 9 was also increased (0.67±0.65 ISU-E; 0.48±0.29 ISU-E and 0.34±0.1 ISU-E, respectively). Sensitization to rAra h 1 and rAra h 3 was not detected. The study of correlation relationships showed the presence of significant direct correlation between sIgE to rAra h 8 and to allergens of other taxonomically different plants, i.e., celery (rApi g 1), apple (rMal d 1) and peach (rPru p 1). We have shown that determination of sIgE only to two allergens Ara h 2 and Ara h 6 allows us to determine primary peanut allergy, which is crucial in predicting severe complications. We have assessed the IgE cross-reactivity profile, thus allowing us to avoid hidden cross-reactions, which may also cause significant sensitization and trigger pathological processes in people with allergic diseases.
Copyright (c) 2026 Samoylikov P.V., Vasilyeva G.V., Konanykhina S.Y., Khlgatian S.V., Zheltikova T.M. https://creativecommons.org/licenses/by/4.0
The role of food hyperreactivity and intestinal microbiota imbalance in development of metabolic syndrome in young volunteers
Prevalence of metabolic syndrome in the world is 20-40%. Due to the high occurence of metabolic syndrome, its early detection is of great importance for timely initiation in order to prevent its eventual complications. Researchers still do not achieved consensus on etiology, diagnosis and treatment of metabolic syndrome. Currently, it has only been shown that there are risk factors for the development of metabolic syndrome such as genetics, lifestyle and disorder of the normal qualitative and quantitative composition of the microbiota. In our opinion, chronic sluggish inflammation and microbiological intestinal dysbiosis play an important role in development of metabolic disorders, and the key predictor of their development is the state of food hyperreactivity. The aim of our work was to assess the role of food hyperreactivity in development of chronic inflammation, metabolic disorders, intestinal dysbiosis and relationships between microbiota, inflammation indexes and metabolic disorders. To achieve this goal, specific IgG antibodies to 111 food antigens were determined using the immunohealth methodology (RZN 2020/9970). Moreover, biochemical indicators of lipid and carbohydrate metabolism, proinflammatory cytokines (IL-6, IL-17), a complete blood count and 33 indicators of intestinal microbiota using PCR (COLONOFLOR-16 (premium)) were evaluated. The study included 60 patients with increased body mass index and 20 volunteers with a normal body mass index. The study material included venous blood samples and fecal samples. The concentrations of cytokines, insulin, and biochemical indicators were determined in blood serum samples. Fecal specimens were used to assess the qualitative and quantitative composition of the colon microbiota. We obtained data indicating the role of food hyperreactivity in development of chronic inflammation and metabolic disorders. We have also shown the role of individual members of intestinal microbiota and their relationship to inflammation and development of metabolic disorders. Thus, we demonstrated an integral relationship between food hyperreactivity, intestinal microbiological dysbiosis, inflammation indices and markers of metabolic disorders. These data may serve as a basis for new approaches to prevention and correction of metabolic syndrome, as well as for further studies of microbiota in various disorders.
Copyright (c) 2026 Cherevko N.A., Novikov P.S., Murzintseva A.A., Vlasyuk E.V., Vekovtsev A.A., Bylin P.G., Kondakov S.E., Rozenshteyn M.Y., Rozenshteyn A.Z., Novikova E.A. https://creativecommons.org/licenses/by/4.0
Polymorphic variants of proinflammatory cytokine genes in affective disorders and in cases of comorbidity with alcohol addiction
Affective disorders and alcohol dependence are among the most common disorders in human population and in general medical practice. Clinical manifestations in comorbid patients with affective and addictive disorders are characterized by heterogeneity and major degree of severity. These conditions occur due to complex biological mechanisms associated with dysregulation of various neuromediator systems. The role of immunoinflammation in development of affective disorders and alcohol dependence is widely recognized, whereas participation of cytokines in pathophysiology of these disorders is still not extensively studied. The aim of the present study was to investigate polymorphic variants of genes encoding proinflammatory cytokines IL6 and tumor necrosis factor α TNFA in patients with affective disorder, and in cases of comorbid states of affective disorder and alcohol addiction. The study included 239 patients with current depressive episode within bipolar disorder, single depressive episode, recurrent depressive disorder, and with dysthymia (F31, F32, F33, F34.1, ICD-10; group F3). Another study group included 69 patients with comorbid course of alcohol dependence (F10, ICD-10) and affective disorder (group F3 + F10) compared with controls (205 mentally healthy individuals). Severity of condition and mental state of the patients was assessment in the course of therapy using SIGH-SAD, SHAPS and SASS scales. Genotyping of DNA samples for the polymorphic variants of IL6 gene marker (rs2069840) and TNFA (rs361525, rs1799964) was performed by real-time PCR technique with QuantStudio™ 5 Real-Time PCR System amplifier (Applied Biosystems, USA) using the Biomaster UDG HS-qPCR Lo-ROX (2×) kits (Biolabmix, Russia), and primers of the DNA-synthesis Company (Russia). The analysis of IL6 polymorphic variants (rs2069840) and TNFA gene (rs361525, rs1799964) showed an evidence for contribution of Т allele of TNFA rs1799964 polymorphism to development of alcohol addiction, and an association of polymorphism rs2069840 of IL6 gene with clinical degree of symptoms in depressive disorders. Our findings confirm the hypothesis about participation of cytokine-regulating gene variants in pathogenesis of affective disorders.
Copyright (c) 2026 Levchuk L.A., Vyalova N.M., Mikhalitskaya E.V., Paderina D.Z., Roschina O.V., Simutkin G.G., Bokhan N.A., Ivanova S.A. https://creativecommons.org/licenses/by/4.0
The role of uNK сells in pathogenesis of abnormal uterine bleeding in women receiving menopausal hormone therapy
Abnormal uterine bleeding (AUB) is frequently observed during menopausal hormone therapy (MHT), thus significantly impairing the quality of life of postmenopausal women and reducing their adherence to treatment. In most cases, AUB associated with MHT is not linked to pathological changes of endometrium. Of note, the role of uterine natural killer (uNK) cells in this process remains unexplored. Our objective was to evaluate the role of uNK cells in pathogenesis of AUB in women receiving MHT. A randomized controlled trial was conducted at the N. Pirogov City Clinical Hospital No. 1 from November 2022 to October 2024, involving 75 postmenopausal women. The participants were divided into three groups: women receiving MHT with AUB (n = 27); females receiving MHT without AUB (n = 25), and postmenopausal women not receiving MHT (n = 23). To perform immunohistochemical analysis and flow cytometry, endometrial samples obtained via pipelle biopsy were examined in a control group (not receiving MHT), and in the study group before MHT initiation, after 6 months of MHT treatment, and during AUB episodes. Women with AUB during MHT exhibited a statistically significant increase in uNK cells in endometrial samples compared to those without AUB (CD3-/CD16+/CD56+: 1.7 (1.46-1.85) vs. 0.66 (0.5-0.79), p < 0.001). Immunohistochemical analysis revealed an increased density of CD56+ cells in endometrial stroma of patients with AUB during MHT. These findings confirm a role of uNK cells in pathogenesis of AUB in women receiving MHT. Further research may contribute to the development of new approaches for prevention and treatment of AUB by means of modulating the uNK cell activity.
Copyright (c) 2026 Dobrokhotova Y.E., Safarli S.E., Ilyina I.Y., Narimanova M.R., Grishin I.I., Raksha A.P., Scherbak E.V., Kazieva M.D., Azimova A.Y. https://creativecommons.org/licenses/by/4.0
Results of newborn screening for inborn errors of immunity in the healthcare system of the Northwestern Federal District of Russian Federation in 2023-2024
The newborn screening program (NBS) plays a critical role in the development of the healthcare system of the Russian Federation. Since 2023, the Order No. 274n “On the approval of the Procedure for providing medical care to patients with congenital and/or hereditary diseases” has extended the scope of neonatal screening. The expanded newborn screening (ENS) includes detection of 36 nosological conditions. Among these, inborn errors of immunity (IEI) represent a significant and still extending group of genetic disorders characterized by increased susceptibility to infections due to underlying immunopathological mechanisms. At the initial stage, quantitative determination of T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) is performed for all newborns in order to identify individuals at risk and initiate confirmatory diagnostics. This approach enables the detection of IEI before the onset of clinical symptoms. This article presents and analyzes the results of ENS program for IEI conducted at the Northwestern Federal District (NWFD) during the period from 2023 to 2024. Over this two-year period, a total of 209,741 newborns were screened at the NWFD. Among them, 818 newborns (0.39% of those screened) were classified as high-risk IEI cases. The immunodeficiency states were identified for 45 children as based on immunophenotyping of peripheral blood lymphocytes (IFT), and genetic causes of the condition were confirmed in 49% of these cases. Statistical analysis revealed associations between gestational age and birth weight with TREC levels, and, to lesser extent, with KREC levels. The reference intervals were established for defined subgroups of neonates. These findings highlight the importance of continuous observation of newborns classified as moderate-risk cases. Notably, 9% of all screened individuals were designated as “conditionally healthy,” despite having TREC or KREC values below the lower reference limit. Based on the obtained data, the models for optimizing the screening program for IEI were proposed. These findings contribute to earlier diagnosis and more effective management of patients with immune disorders, as well as enhanced personalization of therapeutic strategies. Establishing population-based reference intervals plays a key role in standardizing methods for diagnostics and monitoring the immune system, thus representing an important step in overall advances of healthcare.
Copyright (c) 2026 Lobenskaya A.Y., Petrichenko A.K., Evloeva T.U., Kruglikova A.A., Serebryakova E.A., Yalfimova E.A., Marakhonov A.V., Massalskaya M.O., Vechkasova A.O., Morozova A.Y., Koroteev A.L., Tuzankina I.A. https://creativecommons.org/licenses/by/4.0
Arachidonic acid enhances mitophagy and decreases inflammatory response in primary macrophages
Macrophages are actively involved in recognition, capturing, and destruction of foreign pathogens, as well as removal of cellular debris. The most important role of macrophages is to initiate and regulate the inflammatory response: they synthesize and secrete a wide range of proinflammatory cytokines that activate other immune cells and promote the development of inflammation. The functional state of macrophages directly depends on mitochondrial activities, both as energy suppliers, and as key participants in signaling pathways associated with production of reactive oxygen species and inflammasome activation. Mitochondrial dysfunction may lead to excessive macrophage activation and chronic inflammation, typical of diseases like atherosclerosis and metabolic disorders. Damaged mitochondria release components such as mtDNA and cardiolipin, potentially triggering autoimmune responses. To prevent these events, the cells are capable of mitophagy, a selective autophagy process that removes dysfunctional mitochondria via the lysosomal pathway. Polyunsaturated fatty acids are known to influence inflammation and mitochondrial function, including mitophagy. Arachidonic acid, a precursor of prostaglandins and leukotrienes, modulates immune responses, but its role in mitophagy remains unclear. The aim of this study was to investigate whether arachidonic acid affects mitophagy and the proinflammatory response of human macrophages. Primary monocytes were isolated from whole blood of healthy donors and differentiated into macrophages over 5 days. The cells were treated with 20 μM arachidonic acid for 24 hours, followed by 1 μg/mL LPS stimulation for another 24 hours. Cytokine secretion (TNF, IL-6, IL-8, CCL2) was measured by ELISA technique. Mitophagy was assessed using confocal microscopy by evaluating co-localization of mitochondrial and lysosomal dyes. The results showed that arachidonic acid enhanced mitophagy and reduced secretion of TNF, IL6, and CCL2 in response to LPS. These findings suggest that activation of mitophagy may contribute to the anti-inflammatory effects of arachidonic acid in macrophages.
Copyright (c) 2026 Zhuravlev A.D., Nikiforov N.G., Verkhova S.S., Yegorov Y.E., Bagheri M.E., Orekhov A.N. https://creativecommons.org/licenses/by/4.0
Experience with modern techniques of allergy diagnostics in patients with allergic rhinitis in the Republic of Ingushetia
Allergic rhinitis (AR) is a chronic inflammatory condition characterized by episodes of sneezing, rhinorrhea, nasal congestion, and often accompanied by itching in the eyes, nose, and throat. Common AR manifestations include postnasal syndrome, coughing, irritability, and rapid fatigue, which significantly reduce the quality of life. According to epidemiological studies in recent years, the prevalence of AR has significantly increased globally, with estimated frequency of up to 40% in general population. The spectrum of allergens can vary significantly across different regions due to differences in climate and environmental conditions. As a part of a study performed in Republic of Ingushetia, 40 patients seeking medical aid for AR symptoms were examined using modern allergy diagnostic methods. According to the results obtained, 30% of the study group (12 patients) were sensitized to Amb a 1, the allergenic component of ragweed pollen. Sensitization to domestic dust mite allergens (Der f 1, Der p 1) was identified in 8 out of 40 cases (20%). Additionally, sensitization to the major birch pollen allergen (Bet v 1) was found in 6 out of 40 patients (15%). Sensitization to epidermal allergens of animal origin (Can f 1, Fel d 1) was diagnosed in only 4 out of 40 patients (10%). Sensitization to various food allergens was detected in 10% of all examined patients, with the most common substances being wheat (Tri a 14), milk (Bos d 8), and egg (Gal d 1). Sensitization to the major allergen of timothy grass pollen (Phl p 1) was found in 4 out of 40 patients (10%). Sensitivity to the mold fungal allergens (Asp f 1, Alt a 1) was less common, occurring in 2 out of 40 patients (5%). The results of the allergy mapping obtained during the study confirm that the use of specific allergen component diagnostics may significantly increase the accuracy of allergy diagnosis. This, in turn, may facilitate the development of more effective algorithms and personalized techniques for prevention and treatment of AR in each specific case.
Copyright (c) 2026 Pugoeva K., Maksimova A.V., Tataurschikova N.S. https://creativecommons.org/licenses/by/4.0
State of immune homeostasis in hydrographers at the Northern Fleet of Russian Federation, considering their work experience
Labor activity, terms of exposure to professional factors and work experience contribute to modulation of both physiological and psychological functions of the human body. Ecological and climatic features of high latitudes, characterized by almost year-round low temperatures, reduced UV insolation and altered photoperiodism lead to adverse impact of professional activity. The complex of professional and environmental factors is stressful for adaptive abilities, including immune system. The aim of our study was to assess the influence of work experience on the state of immune homeostasis in hydrographers at the Northern Fleet of Russian Federation. A total of 64 practically healthy men working under the conditions of Northern seas were examined, depending on the length of their service: (1) work experience of 2.3±0.4 years; (2) 9.0±0.5 years; (3) 15.9±0.6 years; (4) 28.9±1.0 years. The number of lymphocytes (CD5+, CD10+, CD95+, CD71+) and the ratio of their contents (CD10+/CD95+ and CD71+/CD95+) were determined in peripheral blood using the indirect immunoperoxidase reaction technique with monoclonal antibodies on dried-drop lymphocyte preparations with a peroxidase conjugate stained with a chromogenic solution. The data analysis showed that the number of CD5+ lymphocytes decreases in individuals with up to 9.0±0.5 years of work experience. The ratios of the cell contents CD10+/CD95+, and CD71+/CD95+ varied from 0.94 to 1.06, being within optimal reference values 1±0.05, without any statistically significant difference depending on the length of service. It was found that the suggested mechanisms of immune adaptation proceeds in two ways: in young hydrographers with short and intermediate working experience it is implemented via maintenance of lymphoproliferation-to-apoptosis ratio, due to CD10+/CD95+, along with decreased levels of CD5 marker expression. In older hydrographers with significant and long-term work experience, it proceeds via restoration of CD5 marker expression, along with expanded distribution range of CD10/CD95 ratio and maintenance of CD71+/CD95+ ratio within strict limits. The obtained results suggest a need for individual medical and biological monitoring in order to correct the immune homeostasis of the people working in high latitudes.
Copyright (c) 2026 Kabbani M.S., Shchegoleva L.S., Shashkova E.Y. https://creativecommons.org/licenses/by/4.0
Relationships between the results of lipid profiling, and the levels of matrix metalloproteinases in blood serum in apparently healthy women of different ages
The issues of active longevity are extremely important both for humanity as a whole, and for each individual. There is no unified theory of aging today. Gerontologists agree that aging is caused by many factors that act simultaneously or sequentially. At the same time, most modern theories are based on the study of individual processes occurring during the aging of the body. The aging process alters lipid metabolism by regulating several important pathways involved in lipid transport. In addition, the retention of cholesterol-rich lipoprotein apeS in the artery walls causes several modifications and important biological consequences, including those induced by matrix metalloproteinases (MMPs) which show increased expression with age. The aim of our study was to analyze the values of serum lipid profiling and MMP levels in women of different age, and to assess their interrelations. The study included 157 women, distributed by age (the WHO criteria). The subjects underwent initial medical examination at the clinical bases of the Pacific State Medical University, where the levels of total cholesterol, high-density lipoproteins, low-density lipoproteins, triglycerides, apoliproteins A1, B and MMP values in blood serum were determined. Statistical evaluation of the obtained results was carried out using IBM SPSS Statistics 26 package using nonparametric statistics methods. Results: In conditionally healthy women, depending on age, the total cholesterol levels were high at the age of 45-59 years. In the aged group, this index was significantly reduced. HDL was significantly reduced in the aged group, whereas low-density lipoproteins (LDL) were, on the contrary, increased. The ApoB level was reduced in women under 45 years of age, being increased in the age group of 60-74 years. The ApoB/ApoA1 index was lower in the younger age group compared to women aged > 45 years. In conditionally healthy women, MMP-1 values were higher in the middle-aged group. MMP-2 was higher in the middle-aged group, but its highest levels were recorded among the women over 75 years old. MMP-3 did not show any dependence on age. In women over 75 years old, MMP-7 was lower than the values in other age groups. MMP-9 was higher in the group of women aged 45-59 years. According to results of the correlation analysis, conditionally healthy women showed a direct medium-strength relation between the level of ApoB and MMP-2, which correlated with advanced age.
Copyright (c) 2026 Chepurnova N.S., Jushhuk V.N., Markelova E.V., Visjagina M.A. https://creativecommons.org/licenses/by/4.0
Clinical course of acute respiratory viral infection of various etiology in patients with arterial hypertension
Acute respiratory viral infection (ARVI) is one of the causes of global morbidity. Arterial hypertension (AH) is the most common chronic non-infectious disorder, which may be accompanied by ARVI occurence. The aim of the study is to investigate the clinical features of ARVI of various etiologies (COVID-19, influenza, and unspecified) in patients with arterial hypertension. The retrospective, comparative study included 535 patients divided into three groups: ARVI of unspecified etiology (group 1), 249 persons; COVID-19 (group 2), 250 patients; influenza (group 3), 36 cases. Each of the three groups included two subgroups: A, only ARVI (unspecified, COVID-19, influenza); B, ARVI (unspecified, COVID-19, influenza) accomplished by AH conditioin. Statistical data processing was carried out using STATISTICA 10.0 software packages. The manifestations of intoxication and catarrhal syndrome occurred in patients of subgroups 1A and 1B, their severity was different. In respondents with ARVI and AH (subgroup 1B), the course of ARVI differs in the following parameters: runny nose (χ2 = 4.3; p = 0.040), sore throat (χ2 = 4.3; p = 0.037), fever to febrile levels (χ = 24.5; p = 0.000). The clinical picture in patients with COVID-19 + hypertension differed from patients with COVID-19 without hypertension in that more patients had anosmia (χ2 = 3.84; p = 0.050), headaches (χ2 = 3.84; p = 0.050), myalgia (χ2 = 4.38; p = 0.036), sleep disorders (χ2 = 4.11; p = 0.043), cough (χ2 = 4.18; p = 0.041), prolonged febrile fever (U = 2.01; p = 0.044) (χ2 = 5.74; p = 0.017). Patients with influenza and AH were more likely to report nasal congestion (χ2 = 9.93; p = 0.002), cough (χ2 = 4.11; p = 0.043), and fever (χ2 = 11.25; p = 0.000), which lasted up to 8.5 days (U = 2.59; p = 0.023). For all patients, regardless of the genesis of ARVI in the presence of AH, febrile fever was more common and longer. The manifestations of intoxication and catarrhal syndrome in patients with influenza + AH are distinguished by the complaints of nasal congestion, cough and sleep disorders. In normotensive patients with COVID-19, loss of smell, headache, myalgia, sleep disorders were more common. Knowledge of the clinical features of the course of ARVI of various etiologies in patients with AH will allow for timely therapy correction of both ARVI and AH at the early stages.
Copyright (c) 2026 Antipova E.P., Mordyk A.V., Bagisheva N.V., Moiseeva M.V., Streltsova V.V. https://creativecommons.org/licenses/by/4.0
Сytokine levels during physical exercise and upon meldonium treatment
Signaling molecules (cytokines) play a key role in communications between the immune cells. The main cytokines involved in extracellular matrix remodeling include interleukins and TNFα. IL-6, IL-18 act as pro-inflammatory, and the cytokine IL-10 is anti-inflammatory. TNFα stimulates the production of IL-1, IL-6, IL-18. The cytokine IL-10 affects immunoregulation and inflammation. In recent years, there has been a search for therapeutic agents to correct the cytokine profile. Meldonium is a drug with a broad spectrum of action. The aim of our study was to assess the levels of IL-6, IL-10, IL-18, TNFα during physical activity and when using meldonium. The experiment was conducted in two stages: the first, when the animals performed physical activity without meldonium treatment (n = 36); the second stage (swimming) was performed and combined with simultaneous meldonium treatment (n = 36). A total of 10 swimming sessions were conducted. Meldonium was added to the food of experimental animals for 10 days. The animals were taken out of the experiment immediately after the end of the last session of swimming, and 30 days after the end of the experiments. The concentration of IL-6, IL-10, IL-18, TNFα was determined in blood plasma samples. With strenous physical activity without usage of meldonium, TNFα, IL-6 and IL-18 increased immediately after the experiment and 30 days after the end of the experiments, along with decreased IL-10 levels. Meldonium treatment during heavy physical exercise immediately after the end of the experiment led to a decrease in the level of TNFα, IL-6 and IL-18, along with increased concentration of IL-10 in blood plasma. 30 days after the end of the experiments, the studied cytokines approached the values of the intact group. Heavy physical exercise (without the use of meldonium) led to shifts in the cytokine profile, i.e., the concentration of TNFα, IL-6, IL-10, IL-18 showed sufficient changes. Under the conditions of meldonium use, an increase in the anti-inflammatory cytokine (IL-10) was noted, along with a systemic decrease in TNFα, IL-6, IL-18 levels.
Copyright (c) 2026 Alpidovskaya O.V. https://creativecommons.org/licenses/by/4.0