Vol 28, No 2 (2025)

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Content of BB platelet growth factor in platelet lysates obtained from donor blood

Shupletsova V.V., Khaziakhmatova O.G., Malashchenko V.V., Borisenko S.L., Gabrelyan N.V., Umarova M.M., Goncharov A.G., Litvinova L.S.

Abstract

Cell therapy is among the main methodological approaches in regenerative medicine. Its effectiveness is determined by the use of cell cultures containing the largest available number of viable cells. An important role in this process is played by growth factors that ensure cell proliferation and differentiation. Both recombinant proteins and native proteins from various biological fluids may be used as growth factors. Blood platelets, being anucleate cells, are a promising source of growth factors. Along with their main blood clotting function, the platelets contain a number of unique biological molecules in alpha granules, i.e., mediators involved in immune response, inflammation and regeneration processes. The major families of growth factors present in platelets are: platelet-derived growth factors (PDGF), transforming growth factors (TGF-β), vascular endothelial growth factors (VEGF), epithelial growth factors (EGF), fibroblast growth factors (FGF), insulin-like growth factors (IGFs). The PDGF family includes several subtypes: PDGF-AA, PDGF-BB, PDGF-AB, PDGF-CC, PDGF-DD. PDGF-BB has high angiogenic, chemotactic and mitogenic activity. It takes part in the proliferation and migration of interstitial cells in various organs, proliferation of smooth muscle cells in respiratory tract, development of cerebral vessels and renal glomeruli. The aim of our study was to examine the content of PDGF-BB factor in platelet lysates obtained from healthy donors. Platelet lysate is a complex cocktail containing many growth factors, cytokines, and chemokines. The concentration of specific factors in final product obtained from platelet concentrate is different for each donor, and, apparently, depends on age, gender, blood type and other individual differences. When choosing a growth additive for a cell culture, the cell biologist should be focused on high content of the trophic factor that most closely matches the goals of the given experiment. The use of recombinant additives in the culture medium is justified by precise dosage of these components. However, the use of natural sources may be more preferable, due to presence of different growth factors required for in vitro expansion of highly cellular viable cultures. According to our results, the optimal additive for obtaining viable fibroblasts, endothelial cells, mesenchymal multipotent stem cells is a growth-inducing product obtained from platelet lysate of female donors of Bα (III) group, and male donors of Aβ (II) blood groups which contain the highest concentration of PDGF-BB.

Russian Journal of Immunology. 2025;28(2):171-176
pages 171-176 views

CD44 expression level on different cell lines of hematopoietic origin

Pashkina E.A., Bykova M.V., Berishvili M.T., Krugleeva O.L.

Abstract

CD44 is a hyaluronic acid receptor, a surface molecule expressed on many cells in human body that is essential for some processes, such as cell adhesion and migration. Therefore, this molecule also plays an important role in various aspects of tumor growth, metastasis and invasive processes. High levels of CD44 expression have been found on tumor cells from patients with hematological malignancies, and there is a direct link between CD44 levels and the likelihood of relapse, as well as a dismal prognosis in most hematological malignancies. The purpose of this study was to determine the level of CD44 expression on the surface of tumor cells, namely cell lines of hematopoietic origin.

The expression of CD44 on cell lines 1301 (T cell lymphoma) and K562 (erythromyeloid leukemia) was assessed by flow cytometry.

It was demonstrated that the both cell lines are capable of expressing the CD44 molecule on their surface. In the case of erythromyeloid leukemia cell line K562, a low level of expression of this receptor was observed, while in the case of the T cell lymphoma cell line 1301, the vast majority of cells showed high level of CD44 expression.

In general, the level of expression of this receptor on tumor cells in the case of hematological malignancies may be quite variable in different cell lines of hematopoietic origin.

Russian Journal of Immunology. 2025;28(2):177-180
pages 177-180 views

Analysis of СD4+CD8+ double-positive T cell subpopulations in the patients with immunodeficiencies

Aktanova A.A., Boeva O.S., Skribacheva E.O., Skachkov I.P., Pronkina N.V., Meledina I.V., Zheltova O.I., Krugleeva O.L., Kozlov V.A.

Abstract

Until recently, the studies of pathogenetic mechanisms of different diseases were focused on evaluation of the major cell populations, changes in their quantitative and qualitative characteristics, such as gene expression profile, secreted factors, surface markers, etc. Nowadays, the minor cell subpopulations, their low amounts in peripheral blood are of considerable interest. These cells may function in variable ways, by polarizing the immune response, or participating in regulation of the immune reactions. One of such minor subpopulations is presented by CD4+CD8+ double-positive T lymphocytes which comprise up to 3%, of blood lymphocyte contents. However, these cells are a predominant subpopulation among all T cells in thymus (about 75%). Peripheral double-positive T lymphocytes are a special subpopulation of T cells, because they have no markers characteristic of immature T cells of the thymus, but they bear memory cells antigens, e.g., the CD1a molecule, and a reduced amount of TREC, thus indicating a differentiated mature phenotype. At the same time, these cells may have different phenotypes and functions performed by them. However, the role of CD4+CD8+ double-positive T lymphocytes have not been well studied. There are positive correlations between an increase in double-positive T lymphocytes and demographic and anthropomorphological characteristics, such as age, gender, body mass index. It is known that the contents of this cell subpopulation increase in various pathological conditions, for example, in mononucleosis caused by the Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, hepatitis C, hemorrhagic fever virus, like as in oncological, autoimmune and allergic diseases. Thus, the peripheral CD4+CD8+T cells are assumed to play an important role in regulating immune responses under pathological conditions. We assessed the relative number of CD4+CD8+ double-positive T lymphocytes in immunodeficiencies in different groups depending on age, gender, and certain diagnostic markers, i.e., detection of Staphylococcus aureus, vitamin D deficiency, intestinal or mixed giardiasis, a positive PCR result for a viral infection, and the status of a COVID-19 reconvalescence. We obtained a statistically significant increase of of CD4+CD8+T cell numbers in both men and women, and the number of cells was also changed depending on age, but the selected criteria did not reflect the numerical changes of these cells. A more detailed study on the role of double-positive T lymphocyte subpopulations is necessary, both in immune disorders, and under normal health conditions, because CD4+CD8+ double-positive T lymphocytes can be a significant tool of immune response regulation and sustainability of immunity.

Russian Journal of Immunology. 2025;28(2):181-188
pages 181-188 views

Hormone-producing role of mast cells in reproductive processes: myth or reality?

Valikova O.V., Zdor V.V., Tikhonov Y.N., Boroda A.V.

Abstract

The role of mast cells in the onset and progression of endocrine system dysfunction has been studied for quite a long time, but a clear understanding of their participation has not been obtained. The purpose of the study was to consider the hormone-producing and cytokine-producing functions of mast cells in primary culture in various environments simulating certain hormonal conditions, modeling the level of hormones in follicular fluid during ovulation, to identify the participation of mast cells in the development of endocrine diseases, and to discover new functions of mast cells.

A continuous line of human mast cells HMC-1 (Human mast cell, ATCC) was used, being cultured in IMDM medium (Dulbecco’s modified Eagle’s medium, Sigma-Aldrich). Medium 1 (IMDM) served as a control; medium 2 was an IMDM medium supplied with hormones simulating follicular fluid during ovulation in healthy women, and medium 3 (IMDM) was supplied with hormones mimicking follicular fluid during ovulation in polycystic ovary syndrome. The content of progesterone, testosterone, estradiol, IL-6 was measured on days 1,3,7 of experimental cultures.

Hormonal pattern in the mast cell cultures changed depending on the microenvironment and duration of experiment. The level of estradiol in medium 1 increased more than 80 times compared to the level of estradiol before initiation the cultures. Incubation in medium 2 was followed by 40-fold increase in estradiol by the 7th day of experiment. In medium 3, estradiol levels increased more than 35 times. Testosterone level increased in medium 1 by 3 times; in medium 2, 2.5-fold by the day 7. Upon culture in medium 3, testosterone levels increased 8-fold. IL-6 levels in all media with mast cell culture increased by day 7, but did not exceed the physiological ranges of the cytokine.

A significant progressive increase in the contents of estradiol, testosterone and IL-6 in continuous culture of HMC-1 mast cells observed in different culture media simulating certain in vivo hormonal background suggests an active participation of mast cells in reproductive processes and an independent de novo synthesis of sex steroids and IL-6 by mast cells, which, however, requires a number of confirmatory experiments.

Russian Journal of Immunology. 2025;28(2):189-194
pages 189-194 views

Immunoglobulin E and its significance in chronic dermatoses (psoriasis and vitiligo)

Zhanabaeva G.U., Ismailova Z.A., Muldabekova K.A.

Abstract

The aim of the present study was to specify changes in immunoglobulin E (IgE) in patients with chronic dermatoses (psoriasis and vitiligo). The study involved 168 patients with psoriasis and vitiligo, aged 18 to 65 years, undergoing treatment at the Karakalpak branch of the Republican Specialized Scientific and Practical Center for Dermatovenereology and Cosmetology. IgE levels were determined by means of enzyme-linked immunosorbent assay method (“Vector Best”, Russian Federation). Analysis of the results has revealed an increase in IgE levels in a certain number of patients with different clinical forms of psoriasis. It was established that the IgE level was higher during the progressive stage (191.8 ± 42.95 IU/mL), being 16-fold higher than the values in control group. At the stationary stage, the IgE level in the serum was 10 times higher than the control values, averaging 116.72 ± 20.55 IU/mL. Hences, our studies have shown that the patients with psoriasis living in the Aral region exhibit a significant increase in IgE concentration in blood serum (13 to19-fold over controls). The highest increase in serum IgE was found in patients with erythroderma (19 times over normal range). Analysis of IgE levels in vitiligo revealed an increase in a smaller subgroup of patients. Analysis of patients with elevated IgE levels in vitiligo has shown that these patients had concomitant allergic conditions, i.e., allergic rhinitis and atopic dermatitis. The conducted studies confirm the severity of changes in immune system parameters, including compensatory and reagin-mediated mechanisms, along with activation of cellular autoimmune processes in patients with dermatoses, which vary in intensity depending on clinical severity of the condition. When analysing the changes in IgE levels depending on clinical form of psoriasis, an increase in IgE levels was found in all clinical forms of psoriasis. The highest increase in serum IgE was observed in patients with erythroderma (230 ± 76.91 IU/ mL), which is 19 times higher than in practically healthy individuals. In psoriatic arthropathy (185 ± 44.36 IU/mL) and onychodystrophy (178.33 ± 43.43 IU/mL), it was 15 times higher. In the patients with psoriasis vulgaris, IgE level was 13 times higher (157.77 ± 34.61 IU/mL), and in the palmoplantar form 8 times higher than in controls (95.4 ± 23.05 IU/mL). Upon study of IgE levels in vitiligo, an increase was found in 27% of the total group, whereas 63% showed normal IgE levels. Analysis in the patients with elevated IgE levels revealed that these patients had concomitant allergic pathology manifesting with allergic rhinitis and atopic dermatitis. The patient with the highest IgE level had a family history of psoriasis, i.e., his father had psoriasis.

Russian Journal of Immunology. 2025;28(2):195-200
pages 195-200 views

Detection of allergen-specific Th2A-cells in peripheral blood of patients with allergic diseases

Blinova E.A., Leonova M.I., Nepomnyaschikh V.M., Demina D.V.

Abstract

There is an increase in the incidence of allergic diseases all over the world including Russia. The most common allergic disorders are allergic rhinitis, atopic dermatitis and bronchial asthma. Despite the differences in symptoms, the pathogenesis of all allergic diseases is based on activation of the Th2 immune response. A heterogeneous population of CD4+ lymphocytes is developed in response to allergen. Recently, a group of researchers described a population of terminally differentiated allergen-specific T cells that co-express CRTh2, CD161, and produced high levels of IL-5 and IL-9. This population was called pro-allergic “Th2A” cells. The aim of the present work was to assess the contents of allergen-specific Th2A cells and Th2 lymphocytes in allergic bronchial asthma, atopic dermatitis and allergic rhinitis. The study included 10 patients with allergic rhinitis, 9 cases of atopic dermatitis, 12 patients with allergic bronchial asthma and 8 healthy individuals. Phenotyping of Th2A cells (CD4+CD45RO+CD27-CRTh2+CD161+) and Th2 lymphocytes (CD4+CD45RO+CRTh2+) from mononuclear cells of peripheral blood was performed by flow cytometry. There were no significant differences in the number of Th2 lymphocytes, either between the donor’s group and all groups of patients with allergic diseases, or between groups of patients with different allergic diseases. A 3- to 4-fold increase in the number of Th2A cells compared to healthy individuals was observed in groups of patients with allergic rhinitis, atopic dermatitis, and a 2-fold increase was found in the group of patients with bronchial asthma. Moreover, the level of allergen-specific Th2A cells in patients with allergic rhinitis and in atopic dermatitis was significantly higher than in patients with bronchial asthma. This finding reflects probable involvement of Th2A cells in the pathogenesis of allergic diseases. Th2A cells may be also considered as a potential marker for tracing the course of allergic disease and assessing the efficiency of therapy, thus requiring further research in the field.

Russian Journal of Immunology. 2025;28(2):201-206
pages 201-206 views

Personalized diagnostics and therapy of children with allergopathology in the Kaliningrad region

Marhaichuk A.Z., Gorbunova A.Y., Goncharov A.G., Tuzankina I.A.

Abstract

Allergopathology is a multifactorial group of diseases that includes clinical manifestations from the skin, gastrointestinal and respiratory systems. This group of diseases is based on the mechanisms of hypersensitivity types I, V and VI. These disorders can manifest with similar clinical features. In addition, they must be differentiated from infectious syndrome of primary immunodeficiencies, with onset of an autoimmune disorder, rhinopathy associated with endocrine diseases, enzymopathies. The cohort of children with allergic rhinitis is heterogeneous, due to potentially variable course of hypersensitivity and combination of various pathogenetic pathways. The aim of our study was to develop a personalized approach to diagnosis and therapy in children with manifestations of rhinitis and prolonged cough syndrome. The study included a group of 53 children aged 2 to 18 years who consulted an allergist-immunologist with leading complaints for nasal congestion and prolonged cough. We also excluded infectious factors of hypersensitivity. According to the results of examination and anamnesis, rhinitis was combined with postnasal drip in all patients (n = 53, 100%); episodes of broncho-obstruction and laryngospasm were observed in 20 patients (24%), bronchial asthma attacks – in 7 children (13.2%). Polyresistant bacterial microflora was detected in 20 patients. Allergosensitivity was revealed in 31 children. Rhinopathy associated with alactasia was found in 8 children, with hypolactasia against the background of regular consumption of dairy products – in 5 children. Sanation of chronic flora and dietary therapy was followed by remission of rhinopathy. In 7 patients, the iron deficiency conditions led to sensitivity to bacterial flora. In the structure of sensitization, allergens of house dust mites predominated (61.3%), along with food sensitization (48.4%), epidermal allergens of animals (45.2%), plant allergens (54.67%). In the cases where we identified diagnostically significant allergens, allergen-specific immunotherapy with sublingual (SLIT) drugs was recommended to children. During the year of observation, 12 subjects underwent treatment with house dust allergens; 5, with birch allergens; 3, with a mixture of meadow grass allergens, and one child with wormwood. Some patients still needed pharmacotherapy. After the first course of SLIT, all patients experienced a significant relief of the syndrome. Thus, personalized diagnostics should include a thorough examination: allergy diagnostics, exclusion of gastrointestinal pathology and enzymopathies, detection and sanitation of chronic foci of infections, including parasitic invasions. Such an algorithm may significantly alleviate the severity and duration of clinical manifestations of rhinopathy.

Russian Journal of Immunology. 2025;28(2):207-214
pages 207-214 views

Evaluation of endemic Bet v 1 allergen spectrum at the territory of the Republic of Belarus

Parkhomchuk O.Y., Fomina E.G., Grigorieva E.E.

Abstract

The birch tree occupies the temperate climate region in North America and Europe. Every year between April and May, the birch trees pollinate intensively, which is a common cause of seasonal pollinosis which negatively affects the quality of life in many subjects. Pollen allergy (pollinosis) is among the leading allergic diseases. Sensitization to birch pollen is common in the European regions. Bet v 1 is the main birch pollen allergen which may induce specific IgE in 95% of patients sensitized with birch pollen. Bet v 1 belongs to the PR-10 class of proteins, which includes a large group of aeroallergens and common food allergens. Currently, according to the nomenclature of allergens, 27 variants (isoforms) of Bet v 1 proteins are discerned which may often differ in only several amino acids. The aim of this study was to determine the genetic diversity of the major birch pollen allergen Bet v 1 on the territory of the Republic of Belarus. We studied the pollen samples from birch collected in spring time. Recombinant vector constructs containing genes encoding different isoforms of Bet v 1 allergen were obtained. The nucleotide sequences of the cloned fragments have been determined. Three sequences were found to contain intronic regions interrupting the coding part of the gene. An abridged reading frame was detected in two other sequences. We evaluated the spectrum of Bet v 1 protein isoforms. The sequences obtained are related to 11 genetic variants of the studied allergen to a greater or lesser extent. The majority (86%) of the identified variants correspond to 7 isoforms of 2 isoallergens retrieved in the database of allergenic proteins, with Bet v 1.0101-like sequences being more common (42%), followed by the group with common Bet v 1.0104 variant (19%). The third position (11%) is occupied by Bet v 1.0102-like sequences. The Bet v 1.02 isoallergen is represented by a single variant which is closely similar to the Bet v 1.0204 isoform (3% of the total number of sequences under study). 7 Bet v 1 isoforms were identified within one phylogenetic tree. Bet v 1.0101 (Bet v 1a, X15877.1) was found to be the predominant isoform of the main birch pollen Bet v 1 allergen.

Russian Journal of Immunology. 2025;28(2):215-220
pages 215-220 views

Allergy mapping in immunocompromised patients and patients with helminthiasis in the Republic of Ingushetia

Pugoeva K.B., Maksimova A.V., Tataurschikova N.S.

Abstract

Allergy mapping is a modern technique for diagnosing allergic diseases in immunocompromised patients. Frequent recurrent respiratory viral infections lead to altered classic course in allergic diseases. The aim of the study was to assess the prevalence and spectrum of sensitization in immunocompromised patients and patients with helminthiasis in the Republic of Ingushetia. Allergological examination of patients included prick tests, a blood test for specific IgE using ImmunoCAP. This study was conducted to study the prevalence and type of sensitization in 30 immunocompromised patients aged 18 to 55 years suffering from AR, AtD, PA. Of them, 23 subjects (77%) suffered from allergies and chronic viral infections (CMV, EBV, type 6 HHV, type 1 HSV), with frequent acute respiratory infections, 7 patients (23%) suffered from allergies and parasitic invasions. Food allergies were detected in 7 cases. In these patients, sensitization to Bos d 4 was detected in 57%; to Gal d 1.5, in 43%; to Tri a 14, in 43%; to Mus a, 29%; to Ory 5, in 29% of cases. Most often, patients are susceptible to sensitization to the allergen components of weeds Amb a 1 (30% of cases). Sensitization to beech trees was 17%. Sensitization to the cereal allergens was detected 2 times less often than to trees: 8% of patients were sensitized to the major component of the allergen of Timothy pollen Phl p 1. Most often, patients with helminthiasis were sensitized to food allergens. Of these, Bos d4 sensitization was detected in patient 1 (45%) and patient 4 (50%). Der f 1 demonstrates high sensitization in the patient in patients 6 and 3 up to 30%. Patient 2 exhibited a wide range of allergen sensitization, with significant values for Tri a 14 (35%), Mus a (15%), Bet v 1 (10%) and Phl p 1 (25%). High sensitization to Gal d 1 is observed in patient 3 (30%) and patient 5 (35%). These patterns of sensitization are associated with impaired immunity of intestinal mucosa in the patients with helminthic invasion, which, in turn, is a risk factor for development of sensitization to food allergens.

Russian Journal of Immunology. 2025;28(2):221-228
pages 221-228 views

Expression of "non-classical" MHC molecules in bronchial asthma and atopic dermatitis

Boeva O.S., Borisevich V.I., Abbasova V.S., Kozlov V.A., Demina D.V., Pashkina E.A.

Abstract

Currently, bronchial asthma (BA) and atopic dermatitis (AD) are among the most common allergic diseases. According to available data, the worldwide incidence of bronchial asthma is about 260 million people. Prevalence of BA in adult population is 6.9%, and about 10% among children and adolescents. AD occurs in approximately 10-30% of children and 2-10% of adults in developed countries. Every year, a steady increase in AD and BA incidence is noted, but the pathogenesis of these diseases remains poorly known. Recently, the research is being devoted to the studies of interactions between the immune cells and molecules of the major histocompatibility complex (MHC, human leukocyte antigens, HLA), especially, to “non-classical” HLA. HLA-E are among the less studied antigens. Its gene is located in the short arm of chromosome 6 between the HLA-A and HLA-C genes. HLA-E transcription is found in almost all cell types. HLA-E expression is predominantly present on the surface of lymphoid cells (T and B lymphocytes, monocytes and macrophages), to greater extent, and, to lesser degree, on the surface of endothelial cells. Currently, the role of HLA-E in allergic disorders has not been described in the literature. Therefore, it seems relevant to study the role of HLA-E in allergic diseases, in particular, in bronchial asthma and AD. The biological material for this study were PBMCs taken from the patients with bronchial asthma (n = 19), AD (n = 7) and healthy donors (n = 16). We have found that the proportion of T helper cells carrying surface HLA-E was decreased in allergic disorders when compared to healthy donors. At the same time, the level of HLA-E expression in patients with atopic dermatitis was significantly lower than in patients with bronchial asthma. The level of HLA-E expression on CD14+ and CD8+T cells was significantly lower in patients of the AD group compared to the donor group, whereas no statistically significant differences were observed between the AD group and the donor group. Thus, the level of HLA-E expression on immunocompetent cells differed between the group of donors and the patients with Th2 diseases. A significantly decreased expression of this molecule on immunocompetent cells of the patients with bronchial asthma may suggest a possible role of this molecule in pathogenesis of this disease.

Russian Journal of Immunology. 2025;28(2):229-234
pages 229-234 views

A new marker of eosinophilic inflammation in patients with chronic obstructive pulmonary disease

Kuznetsov V.D., Kozlova Y.I., Sobolev A.V., Frolova E.V., Uchevatkina A.E., Filippova L.V., Vasilieva N.V.

Abstract

Chronic obstructive pulmonary disease (COPD) is one of the most common bronchopulmonary diseases. Eosinophilic inflammation of the respiratory tract in COPD requires further search for new markers for diagnosis and determination of further therapy strategy. Aim: determination of periostin level and assessment of its significance as a marker of eosinophilic inflammation in patients with COPD.

The study included 45 patients with COPD (males at median age of 65). Medical history, results of clinical and instrumental studies were evaluated. The levels of total IgE and periostin were determined in blood serum by enzyme immunoassay. The obtained data were processed using the software systems STATISTICA 13 and SPSS Statistical 27.

On the basis of peripheral blood eosinophils, the patients were divided into a group with eosinophilic inflammatory endotype (9 patients, males aged 67), and a non-eosinophilic endotype (36 patients, men aged 65 years). The patients with eosinophilic endotype of COPD had a later onset of the disease [64 (61-65) years vs 56 (49-60); p = 0.011], and a significantly higher proportion of patients with a history of atopy (80% vs 0%; p < 0.001). In patients with non-eosinophilic COPD endotype, a significantly lower FEV1/FVC index was found [46 (44-51) % vs 54 (54-73) %; p = 0.019]. The serum periostin level in patients with the eosinophilic endotype of COPD was 21 (20-22) ng/mL thus being significantly higher than in the group with the non-eosinophilic endotype [14.5 (12-18) ng/mL; p = 0.008]. Using ROC analysis, it was found that a periostin value of more than 19.5 ng/mL is the optimal cut-off point for detecting the eosinophilic endotype in patients with COPD thus serving an additional potential predictor of a positive response to inhaled glucocorticosteroid therapy (ICS) [AUC was 0.940 ± 0.060 with 95% CI: 0.822-1,000, sensitivity of 80%, specificity of 80% (p = 0.007)].

Periostin is a promising marker of eosinophilic inflammation in patients with COPD. Its elevated level may be considered an additional criterion for the administration of ICS therapy.

Russian Journal of Immunology. 2025;28(2):235-240
pages 235-240 views

Vitamin D in blood serum and "skin window" cytokines in atopic dermatitis with concomitant atopies

Zagreshenko D.S., Kukharev Y.V., Klimov A.V., Klimov V.V., Rakhmanova M.M., Musina M.I., Shkatova A.N., Slezkin M.I., Khardikova S.A., Pestova V.V., Yakovenko I.S., Barkova I.Y., Rachenkov K.A.

Abstract

Atopic allergic diseases are widespread in the world. Due to common pathogenesis, various atopies are often combined within this group. Therefore, multiple atopic comorbidity is common phenomenon. To date, atopic dermatitis is one of the most common chronic recurrent skin diseases. Atopic dermatitis is an allergic condition with pronounced local inflammatory events in the skin. Meanwhile, allergic rhinitis (68%), allergic conjunctivitis (22%), atopic bronchial asthma (22%), acute urticaria (19% of cases) were detected as concomitant atopic diseases in patients with this disorder. In our study, local concentrations of pro-inflammatory cytokines IL-6, TNFα, as well as inflammasome-mediated IL-1β and IL-18 were measured using “skin window” technology. In blood serum, the level of vitamin D was determined by electrochemiluminescent analysis in 68 patients with allergies aged 18-45 years and in 62 healthy persons. It was found that the serum levels of vitamin D were significantly lower among the patients with atopic dermatitis, than in control group. The contents of cytokines IL-1β, IL-18, IL-6, and TNFα in “skin window” exudate in atopic dermatitis significantly exceeded similar indexes in the control group. The results of our study suggest an important influence of vitamin D on pathogenesis of atopic disease. In cases of vitamin D deficiency, its clinical course may be aggravated, whereas its increase in blood serum is associated with a decrease in pro-inflammatory cytokines released in the skin. Overproduction of IL-1β and IL-18 indirectly implies the development of intracellular inflammasomes. A negative correlation between the values of vitamin D and inflammasome-mediated cytokines was observed both in atopic dermatitis and in healthy donors. This finding may indicate not only the involvement of vitamin D in pathogenesis and course of this disorder and other concomitant atopies, but may also cause a possible contribution of vitamin D to inhibition of inflammasome assembly and activation.

Russian Journal of Immunology. 2025;28(2):241-246
pages 241-246 views

Specific antinuclear antibodies in different fluorescence patterns of antinuclear factor on the HEp-2 cell line in children with autoimmune diseases

Zhuzhula A.A., Kurbatova O.V., Snovskaya M.A., Fisenko A.P., Petrichuk S.V., Konopleva T.N., Semikina E.L.

Abstract

Antinuclear antibodies (ANA) are a family of autoaggressive antibodies directed against different components of the nucleus and cytoplasm of cells. The detection of ANA is of primary importance for the laboratory diagnosis of autoimmune diseases (AID). The aim of our study was to compare the presence of specific antinuclear antibodies with different types of antinuclear factor luminescence in children with autoimmune diseases using the HEp-2 test cell line. The study included 40 children (34 girls and 6 boys) with AID who were being treated at the National Medical Research Center for Children’s Health. The age of the patients ranged from 6.28 to 17.99 years. All children were diagnosed with antinuclear factor (ANF) on the HEp-2 cell line (epithelial cells of human laryngeal cancer) by means of indirect immunofluorescence reaction (AESKUSLIDES® ANA-HEp-2, Germany) using a HELIOS® analyzer (AESKU.GROUP, Germany). ANA was determined using a Q-Processor analyzer using Protea ANA Profile 18 panels (ProteomeTech Inc., Korea), which applies the immunoblot analysis method for the qualitative detection of autoantigen-specific IgG antibodies. A positive ANF titer was detected on the HELIOS® analyzer in all children with AIS (100%). Using the Protea ANA Profile 18 panel, specific ANA was identified in 75% of patients (30 children). In our sample of children with AID, homogeneous (AC-1) and nuclear large-granular (AC-5) types of ANF luminescence, as well as their combinations, were most often detected. In the homogeneous type (AC-1) of ANF glow, autoantibodies to dsDNA, Nucleosome and Histone were more often detected. In large-granular nuclear (AC-5) antibodies to RNP 70, RNP A and RNP/Sm were determined, in combination with AC-1 + AC-5 – to SSA 60, SSA 52, Nucleosome and Histone, RNP 70, RNP A. We identified single points in the nucleus (AC-7) in 10% (4 children), this type of ANF glow is characterized by a low positive prognostic value. The study of ANF and specific ANA using the Protea ANA Profile 18 panel revealed a coincidence in 75% of cases, and certain ANA are consistent with the types of ANF luminescence. In pediatric diagnostics, it is advisable to determine a wide range of ANA when detecting antinuclear factor on the Hep-2 cell line.

Russian Journal of Immunology. 2025;28(2):247-254
pages 247-254 views

Features of the autoantibody profile in women with systemic lupus erythematosus and endometriosis

Aleksandrova N.V., Zborovskaya I.A., Aleksandrov A.V., Korenskaya E.G., Emelyanov N.I.

Abstract

Endometriosis is a chronic inflammatory disease of women, occurring primarily during reproductive age, with high incidence of various autoimmune diseases such as systemic lupus erythematosus (SLE). SLE is characterized by a variety of clinical manifestations and hyperproduction of various antinuclear antibodies. Their role in pathogenesis of endometriosis is actively discussed. We have collected clinical and laboratory data of 53 women (mean age 39.5±9.3 years) with chronic SLE who had gynecological reports on negative or positive assessment of endometriosis, in order to evaluate the patterns of autoantibody profile in women with SLE, dependent on the presence of endometriosis. We determined the following antibodies: antinuclear factor (ANF) by indirect immunofluorescence on HEp-2 cells; antibodies to double-stranded DNA (anti-dsDNA), antibodies to Smith antigen (anti-Sm-IgG), to cardiolipin (IgG/IgM), and to β2-glycoprotein-I (anti-β2GP-I) using appropriate immunoassay kits. The levels of anti-DNA and anti-Sm-IgG were higher in subjects with endometriosis, but the differences did not reach statistical significance (p = 0.068 and p = 0.079, respectively). Similarly, no intergroup differences were observed for antibodies to cardiolipin of different classes and anti-β2GP-I (p > 0.1). A higher proportion of patients with positive ANF titers (> 1:160) was found in the group of SLE patients with endometriosis (p = 0.034), with antibody titer > 1:320 found in 64.7% of these patients. All ANF-positive samples were diluted to a final titer of 1:1280 and characterized by the type of nuclear staining. The most frequent pattern was homogeneous (45.3%) and granular (41.5%), which combined fine-granular, coarse-granular, and dense fine-granular types of luminescence. Granular type of luminescence was more frequently detected in patients with endometriosis (11/17 vs. 11/36; χ2Yates, p = 0.04), reflecting the reaction of autoantibodies with nucleoprotein complexes. When several types of ANF luminescence were detected in the same sample, one of them (usually at low titers) interfered with others, and changed when the dilution titer was increased to 1:640 – 1:1280 (9 individuals with different transition variants). It seems that the characterization of ANF luminescence type may provide more valuable information in future management of SLE patients with comorbid pathology. Further studies are needed to evaluate the role of ANF in pathophysiologic mechanisms of endometriosis in SLE.

Russian Journal of Immunology. 2025;28(2):255-262
pages 255-262 views

Point mutations in the mitochondrial genome of skeletal muscle in patients with osteoarthritis

Goncharov A.G., Jigkaev A.K., Lobanova V.V., Kozenkov I.I., Khaibulin E.V., Popadin K.Y., Gunbin K.V.

Abstract

Osteoarthritis (OA) is one of the most common diseases of the musculoskeletal system, accomplished by a high level of disability. The leading pathogenetic factors of these age-associated diseases include the interrelated processes of “inflammatory aging” and mitochondrial dysfunction, which lead to the development of chronic inflammation and degradation of different joint tissues. The present article contains results about point mutations in mitochondrial genome of peri-articular muscular tissues in the patients with primary OA (experimental group) and post-traumatic osteoarthritis (control group). The study involved 67 volunteers over 53 years old with basic diagnosis of post-traumatic or primary gonarthrosis / coxarthrosis stage 3. Clinical diagnosis was made on the basis of medical history, complaints, clinical and X-ray examination data. The material for the study included the samples of muscles (80 to 100 mm3) obtained at knee or hip replacement surgery. Several techniques have been adapted for isolation, enrichment and purification of nucleic acids, thus allowing to obtain up to 500 ng of mitochondrial DNA (mtDNA) from the biopsies. The prepared mtDNA libraries were sequenced at NGS platform. Bioinformatic analysis was carried out using the following programs: MitoHPC (to detect rare single-nucleotide mutations of mtDNA), MitoSAlt (to detect rare deletions at the mtDNA level) and Splice-Break2 (to detect rare deletions at the level of mtDNA RNA transcripts). Common point mutations A189G (adenine to guanine at position 189) and T408A (thymine to adenine at position 408) were detected. In the control group, the A189G mutation was revealed in 7 patients and T408A mutation was found in 8 volunteers (both mutations were detected in 6 out of 9 persons). In experimental group, the A189G mutation was found in 43 of 58 patients, T408A – in 35 volunteers. In this group of volunteers, both mutations were registered in 19 subjects. The level of mutation frequency, expressed as allele frequency (VAF) in the experimental group significantly exceeded that of the control group. Moreover, in experimental group, unlike control group, a significant correlative relationship was established between the presence of an increased level of mutations in the mitochondrial genome, and a number of clinical and laboratory parameters in volunteers. The described mutations in the mitochondrial genome of periarticular muscle tissue seem to be associated both with aging process and with the direct development of age-associated pathology, i.e., osteoarthritis. The increased levels of mutations in positions 189 and 408 of the regulatory region of mitochondrial genes detected in our patients are apparently associated with both increased level of mutations typical of pathological aging and, possibly, with genotoxic effects of high-dose therapy with non-steroidal anti-inflammatory drugs on mitochondrial genome.

Russian Journal of Immunology. 2025;28(2):263-270
pages 263-270 views

Effect of Helicobacter pylori infection on bone mineral density in patients with rheumatoid arthritis

Aleksandrov A.V., Shilova L.N., Aleksandrov V.A., Krasilnikov A.N., Emelyanov N.I., Alekhina I.Y., Aleksandrova N.V., Zborovskaya I.A.

Abstract

The ability of Helicobacter pylori (H. pylori) to develop and maintain chronic inflammation, induce general immune response, to affect blood lipid metabolism and insulin resistance, and negative impact on bone mineral density (BMD) requires a closer look at the association between H. pylori infection and secondary osteoporosis (OP) in patients with rheumatoid arthritis (RA). The effects of H. pylori infection on BMD at the axial skeletal sites were assessed in 85 women with RA (35 patients were diagnosed with OP). Blood serum samples from RA patients were tested for the presence of IgG class antibodies to H. pylori (anti-Hp-IgG) and total antibodies to H. pylori CagA antigen (anti-CagA). When anti-Hp-IgG was determined, a positive result was recorded in 70.6% of cases. Anti-CagA was also detected in 34 patients with chronic H. pylori infection. In the total group of patients infected with H. pylori, there was a decrease in spinal BMD at the level of L1-4 (BMDL1-L4, p = 0.008), but not in total hip BMD (BMDTotal) (p = 0.06). The analysis of variance demonstrated a significant decrease in both BMDL1-L4 (p = 0.01) and individual BMD parameters of the proximal femur (BMD of the femoral neck, BMDNeck, p = 0.048 and BMD in the Ward’s zone, BMDWards, p = 0.02) detectable only among patients positive for anti-CagA. Among RA patients with a confirmed diagnosis of OP, the incidence of H. pylori infection was significantly higher than in the group of RA patients without osteoporosis (÷2, p = 0.021), and the major proportion of patients with OP were also positive for anti-CagA (73.3%). In patients with significantly high titers of anti-CagA (n = 16), the decrease in BMD was most pronounced and differed from the BMD values for axial skeletal support sites in the group of patients with low titers of these antibodies (BMDL1-L4, p = 0.003; BMDNeck, p = 0.011; BMDTotal, p = 0.049). Infection with H. pylori strains expressing CagA may be considered not only as a risk factor of osteopenia and osteoporosis, but also as a possible risk factor for low-energy fractures in RA patients. Moreover, it seems that the high anti-CagA titers may predict a risk of developing OP in H. pylori-infected patients with RA, rather than simple detection of helicobacteriosis or infection with a CagA-expressing strain. In summary, the presence of chronic H. pylori infection is accompanied by a decrease in BMD across axial skeletal support sites, and H. pylori infection should not be ignored in the treatment of osteoporotic complications in patients with RA.

Russian Journal of Immunology. 2025;28(2):271-278
pages 271-278 views

Polymorphisms of cytokine genes and their correlations with efficiency of continuous treatment in patients with pulmonary tuberculosis

Alymenko M.A., Valiev R.S., Valiev N.R., Balabanova N.P., Kolchanova N.E., Polybin R.V., Shepel R.N., Lipatov V.A., Kolomiets V.M.

Abstract

Current research in the field of an immunogenetics of tuberculosis is considered a key direction, since the treatment efficiency and outcomes of the disease in most cases depend on immunological and genetic features of the patient. Special attention should be paid to IL-10 value in development of protective immunity against tuberculosis. There are some contradictory data on influence of IL-10 on development of immune response in the patients with pulmonary tuberculosis which are published in several works. For example, L.G. Tarasova and colleagues connect the increased concentration of IL-10 with extensive destructive processes in pulmonary tissue, whereas while D. Higgins and coauthors show its key role in protection against chronic pneumonia. The objective of our study was to evaluate relations between several cytokine gene polymorphisms (IL1β, IL4, IL10, TNF), and their expression levels of in the course of continuous chemotherapy.

Whole venous blood was taken for the molecular and genetic analysis was perfoemed, with subsequent isolation of genomic DNA and carrying out real-time PCR for genotyping of SNPs. Concentration of cytokines in blood serum were defined by method of enzyme immunoassay. Statistical analysis included check of normality of distribution of data, nonparametric correlations and comparison of qualitative characters. The assessment of compliance of genotypes to distribution of Hardy–Weinberg was carried out with use of criterion χ2 Pearson. To measure the cytokine concentrations (IL-1β, IL-4, IL-6, TNFα, IFNγ, IL-10) in blood serum, we used peripheral venous blood taken in fasting state at a 5-mL volume. Enzyme immunoassay was made with reagent sets from JSC Vektor Best-Tsitokiny according to the instructions from manufacturer.

In the course of specific chemotherapy at the continuation phase, a more adverse course of a disease was registered among the patients with a pulmonary tuberculosis harboring IL4-589CC genotype, when compared with those who have IL4-589CT+TT genotype. In the persons with IL10-592CA+AA genotype, a less favorable course of the disease was observed at the intensive phase of therapy, in comparison with patients who had IL10-592CC genotype.

Thus, process of interaction between microorganisms and macroorganisms in case of a tuberculosis infection represents a quite complicated process involving a set of immune response elements. Interactions within this system are controlled by means of cytokines, the mediators of cellular interactions.

Russian Journal of Immunology. 2025;28(2):279-286
pages 279-286 views

Ambivalent in vitro effect of immunoregulatory peptides on antigen-presenting subsets of neutrophil granulocytes in purulent inflammatory diseases

Nesterova I.V., Chudilova G.A., Teterin Y.V.

Abstract

Neutrophilic granulocytes (NG) are functioning as regulators of the immune response. Expression of NG molecules HLA-DR and presentation of antigen to T cells is one of their regulatory mechanisms. The NG dysfunction plays a great role in pathogenesis of acute hematogenous osteomyelitis (AHO) in children. An activated, antigen-presenting NG subset (APC) СD66b+CD16+CD33+HLA-DR+ was also found in these patients. Therefore, studies of surface NG membrane receptor expression, including HLA- DR, their regulation by peptides, and influence of the latter factors on correction on NG effector functions are of sufficient interest. Our objective was to evaluate the possibility of in vitro modulating the phenotype of CD66b+CD16+CD33+HLA- DR-, CD66b+CD16+CD33+HLA-DR+ subsets of neutrophilic granulocytes under the influence of hexapeptide (HP) and glucosaminylmuramyl dipeptide (GMDP) in blood cells of children with acute hematogenous osteomyelitis using in vitro experimental tests.

Peripheral blood (PB) of 28 children with AHO aged 8-15 years was studied (the study group). 13 healthy children aged 8-15 years comprised the comparison group. To evaluate the effect of peptides, PB of children with AHO was cultured with HP (10-6 g/L, 60 min, 37 °С): study group 1, and with GMDP (10-6 g/L, 60 min, 37 °С) – study group 2. The number of NG CD66b+CD16+CD33+HLA-DR+, CD66b+CD16+CD33+HLA- DR- subsets, receptor expression density (MFI) (FC 500 “Beckman Coulter”, USA), phagocytic activity of NG, before and after cultivation were tested with these peptides.

In children with AHO, a subset of NG CD66b+CD16+CD33+HLA-DR+ is registered in 30.2 (16.4-34.9) %; with MFI, HLA-DR it comprised 3.5 (3.3-4.2) %. Under the influence of HP, a decrease of NG-APC and MFI HLA-DR numbers to 1.7 (1.6-2.2) (p1.2 > 0.05) was revealed, due to binding of HP to HLA-DR (p > 0.05). Under the influence of GMDP, there is a significant increase in MFI CD66b and MFI CD33 receptors (p1.2 < 0.05) in both subsets; there is an increase in MFI HLA-DR (p > 0.05) in the NG-APC subset. The modulating effects of HP and GMDP on the phenotype of NG CD66b+CD16+CD33+HLA-DR+ and CD66b+CD16+CD33+HLA- DR- subsets may contribute to restoration of the phagocytic function of NG.

We have detected the “long-lived” activated NG subset CD66b+CD16+CD33+HLA-DR+ with the properties of APC, that can present antigen to T lymphocytes in PB of children with AHO. However, the important question exists, whether such a transformation will promote or slow down the progression of the purulent-inflammatory process? In this study, we have demonstrated in vitro the ability of two immunotropic peptides (HP, GMDP) to modulate the phenotype of NG-APC subset, thus potentially promoting recovery of the NG effector functions.

Russian Journal of Immunology. 2025;28(2):287-294
pages 287-294 views

Correction of the condition in HIV-infected patients with Spirulina

Akhmedjanova Z.I., Urunova D.M., Akhmedzhanov R.I.

Abstract

The damage to the immune system during HIV infection is of systemic oriigin, manifesting by deep suppression of the T- and B-links of cellular immunity. Particular importance in the normal functioning of all physiological systems is given to microelements, which are cofactors of at least 2000 enzymes that catalyze multiple biochemical reactions. Our study concerned measurent of 26 macro- and microelement contents in the hair of HIV-infected patients. It was carried out using the method of neutron activation analysis at the Institute of Nuclear Physics at the Academy of Sciences of the Republic of Uzbekistan. The parameters of immunity were evaluated in 50 patients with HIV infection at the Institute of Human Health (Academy of Sciences of the Republic of Uzbekistan). A significant decrease in Cl, Ca, K, Zn, Fe, Cu, Se, Cr, Ag, Co, Au, Ni, Sr, Ba, Hg, Sb, Cd, Rb was revealed in the group. Correction of this condition in HIV-infected persons and macro- microelement status was attempted using Spirulina microalgae as a dietary supplement, a product of natural origin. An analysis of Spirullina tablets was carried out, and the contents of 23 macro-microelements have been specified. The results of our study showed that clinical condition and quality of life was improved in 84% of patients after a month of taking Spirulina. Their physical performance was increased, general condition has been improved, and according to the patients, “the vital tone has increased.” Indices of immune status and contents of macro-microelements have been also improved.

Russian Journal of Immunology. 2025;28(2):295-298
pages 295-298 views

An approach to comprehensive assessment of the post-COVID quality of life in the children

Makhmutov R.F., Dubovaya A.V., Likhobabina O.A.

Abstract

The scientific literature around the world reports on the increasing problem of post-COVID syndrome in children affecting their quality of life. Post-COVID syndrome is a clinical condition that occurs several weeks after an episode of acute COVID-19 infection, which resulted in clinical recovery accompanied by nonspecific neurological symptoms, skin vasculitis, mental disorders and impaired functions of different organs. Significant difficulties in diagnosis and medical and preventive measures are caused by the lack of accurate definitions and diagnostic criteria, which currently allows us to determine post-COVID syndrome as a “diagnosis of exclusion”. The purpose of our present study was to develop an approach to comprehensive assessment of the life quality in children with post-COVID syndrome.

COVID-19 infection was diagnosed on the basis of anamnestic data, medical repotrts, results of clinical, laboratory and instrumental studies, consulting with narrow specialists, in accordance with the “ICD 10th revision”. An objective assessment of QOL was based on a set of indices of general clinical blood and urine tests, biochemical parameters, evaluation of immunological status, cardiovascular system, autonomic nervous system, psychoemotional status, and the state of cognitive functions. We studied the initial vegetative tone, the level of memorization, the stability of attention and the performance dynamics, work efficiency, degree of working ability and mental stability, self-assessment scale for the anxiety levels. To diagnose the psychophysiological state of the persons, determine their requests and needs, expectations and attitudes, volitional abilities and stress coping, to assess relationships with people, analyze sources of stress, anxiety, and internal conflicts, the Lusher method (color test) was used.

The study has shown development of vegetative, psychoemotional and cognitive disorders after COVID-19 infection, which cause significant discomfort in daily life in children and adolescents which persist for a considerable time, which, in turn, significantly reduces the quality of life in children and adolescents with post-COVID syndrome.

The developed method of comprehensive quality of life assessment in the children with post-COVID syndrome is aimed at determining clear objective criteria for assessing the quality of life, thus allowing further evaluation of life quality in this patient population, but also specify medical control over all children and adolescents, and those who suffered from COVID-19, and require further observation by neurologists, psychoneurologists, neuropsychologists, speech therapist, psychologist and psychiatrician.

Russian Journal of Immunology. 2025;28(2):299-306
pages 299-306 views

Features of clinical blood biochemistry in patients who have suffered a new coronavirus infection

Sadowski I.S., Kruglova O.S., Savchenko A.A., Sobko E.A., Kasparov E.V., Demko I.V., Borisov A.G.

Abstract

The COVID-19 pandemic, which began in December 2019, was caused by the new coronavirus SARS-CoV-2. SARS-CoV-2 is a shell virus containing a single positive chain genome and using angiotensin converting enzyme 2 (ACE2) as a cell entry receptor. The targeting of SARS-CoV-2 on several tissues expressing ACE2 explains the multifactorial pattern of symptoms: fever, dry cough, myalgia, fatigue and shortness of breath. These symptoms do not always stop after COVID-19, and symptoms may reappear within 12 weeks, which indicates the development of post-COVID syndrome (long COVID). Due to the extensive symptoms and comorbidity of patients, the clinical diagnosis of post-COVID syndrome is difficult. The aim of the study is to identify pathognomonic indices of biochemical blood analysis in convalescents, indicating the development of post-COVID syndrome.

Patients and study design: a retrospective observational one-moment study of 373 case histories and outpatient records was conducted for the patients exposed to COVID-19 not later than 12 weeks ago. The initial course of the disease (disease) was assessed using the WHO Clinical Progression Scale. The severity of post-COVID syndrome (clinical outcomes) was assessed on the functional status scale after COVID-19 (PCFS). All subjects are divided into four groups, the names of which reflect the severity of COVID-19 and the severity of the post-ovoid condition: 1st group, “mild COVID-19 / 0-2 PCFS class”; 2nd group, “mild COVID-19 / 3-4 PCFS class”; 3rd group, “medium and severe COVID-19 / 0-2 PCFS class”; 4th group, “medium and severe COVID-19 / 3-4 PCFS class”. The sample was described by calculating the median (Me) values and interquartile range expressed as Q1 and Q3 (Q0.25-Q0.75). The reliability of the differences between independent samples was assessed with nonparametric Mann–Whitney U-test and the Student’s t-test.

Upon evaluation of clinical blood biochemistry, the alanine aminotransferase (ALT) level in group 1 was higher than in groups 2 and 4, the aspartate aminotrasferase (AST) level in group 2 was higher than in groups 1 and 3. The indexes of total cholesterol and LDL did not show statistically significant differences between the groups. Creatinine levels in group 3 are higher than in group 1, being lower in group 4 than in other groups. Significant differences were observed upon qualitative assessment of C-reactive protein (CRP). There were 2-3 times more subjects with elevated CRP levels in groups 2 and 4 than in group 1.

A minimal biochemical profile, including an assessment of the level of transaminases and creatinine, a qualitative or quantitative assessment of C-reactive protein, may indicate development of chronic inflammation. Patients of this group need to undergo an additional examination, e.g., general urine analysis and determination of albumin level in urine, dynamic GFR calculation, in order to prevent the development of persistent renal impairment.

Russian Journal of Immunology. 2025;28(2):307-314
pages 307-314 views

Fever: current view on its significance in the COVID-19 era and the people’s attitude to this symptom

Najdenkina S.N., Ermakova M.K.

Abstract

Our purpose was to evaluate the scientific data on occurrence of fever in the infectious conditions as well as studying peculiar features of fever in children at pediatric unit with assessment of attitude towards pyrexia among general population. Fever is a general response to infection which occurs across warm- and cold-blooded vertebrates for over 600 million years of evolution. The response to fever is mediated by integrated physiological and neural circuitries and provides a survival advantage during infection. The world experience in fever studies shows an ambiguous effectiveness of combating it, both under septic conditions and non-septic events. In a systematic review of 42 studies conducted by Rumbus Z. and other authors, the mortality rate in patients with sepsis with fever greater than 38 °C was 22.2%, with normothermia – 31.2%, and was highest in patients with hypothermia less than 36.0 °C – 47.3%. That is, fever was associated with reduced, and hypothermia with increased mortality in septic patients. All attempts to achieve improved survival by usage of antipyretics and physical cooling in sepsis have failed. Given the rising mortality rates during the COVID-19 pandemic, we may neglect a key aspect of the immunological response. Higher body temperature inhibits growth of microorganisms, enhances the effects of antibiotics on bacteria in biofilms, improves the survival of neutrophils, stimulates interferon productions. The heat shock proteins have a cytoprotective effect; the pyrogenic cytokines stimulate lymphocyte differentiation and exert other significant effects. However, the mechanisms of switching from pro-inflammatory to anti-inflammatory response as well as the origins of cytokine and septic shock remain understudied. It is important to look at pyrexia from the viewpoint of the body integrity. The continuum theory (unified theory of diseases) suggests that the constant fight against fever and acute inflammation causes a transition from a response to the pathogen to another, first subacute and, later to chronic level of inflammation, which excludes the possibility of acute inflammation being a predictor of ageing.

The presented review of some chronic inflammatory diseases showed this age dependence. In clinical histories, a decreased frequency and severity of fever may be observed during the onset of such chronic diseases as diabetes mellitus, bronchial asthma, chronic headaches, hypertension and post-viral syndrome. This trend suggests a revision of approaches to treatment of acute inflammation in general population. Pediatric patients exhibit the most pronounced fever and have less common chronic diseases overall. However, in recent decades a trend is noted for increase in chronic diseases among children. What is the cause of pediatric fever, and how common is usage of antipyretic drugs and other methods of fever therapy in general population? For this purpose, 300 parents living in the rural areas, and 300 urban parents of children aged 4 to 5 years have been surveyed during the non-epidemic period upon their visit to pediatric polyclinics.

Fever was most often a sign of acute respiratory infection (82.0% of cases); other acute inflammatory conditions were less common. Duration of pediatric fever exceeded 3 days in 77.0% of patients, its grade was < 39% (58.0% of the cases). High febrility was observed in 40.3% of patients and hyperthermia above 41 °С – in 1.7% of children. In the studied cohort, 21.0% had documented diseases; chronic inflammatory diseases were observed only in 9.0% of cases. With pyrexia, 96.3% of parents are anxious, have a fear of fever and use antipyretic drugs and other treatment. Febrile seizures were observed in 3.3% of pediatric patients, other adverse events were observed in 10.3% of respondents. The reported pyrophobia among the population is not justified, since fever in the child population is, generally, a sign of acute infectious disease with high temperature being is a protective reaction. The fight against pyrexia can adversely affect not only the further course of the disease, but also affect the health condition in the future, actively interfering with serious pathogenetic mechanisms.

Russian Journal of Immunology. 2025;28(2):315-320
pages 315-320 views

Dynamic evaluation of peripheral blood cytokines in former COVID-19 patients with acute coronary syndrome

Safronova E.A., Ryabova L.V., Zurochka A.V., Dobrynina M.A., Praskurnichy E.A.

Abstract

The purpose of this study was to evaluate the level of cytokines in the blood serum of patients with acute coronary syndrome (ACS) who had and did not have COVID-19 in the dynamics of the disease and treatment. Our objectives were as follows: To identify groups of patients with ACS who had previously suffered from COVID-19 and who did not have this disease; to determine cytokine levels initially and over time in 2 groups of patients, i.e., those with and without previous COVID-19. Measurement of cytokine levels was carried out in 20 male patients with ACS without a history of COVID-19 and ACS patients with post-COVID syndrome. The contents of cytokines were determined by multiplex analysis on a MagPix 100 device using a test system from BioRad (USA) for 17 cytokines. As based on the data obtained, one may note that in patients who recovered from COVID-19, compared with persons without previous COVID-19, IL-10, IL-1β, IL-8 levels were significantly lower, and IL-13, IL-6, MCP-1 contents were increased. In the course of time, a statistically significant decrease (p < 0.05) was found in patients who had previously had COVID-19 for IL-10, IL-13, IL- 2, IL-6, MCP-1, MIP-1β, TNFα, whereas IL-8 levels were increased (p < 0.05). In patients without a history of COVID-19, a statistically significant decrease was revealed in dynamics for IFNγ, IL-6, MCP-1, MIP-1β, TNFα, along with increase in IL-8 contents (p < 0.05). Patients with post-COVID syndrome, compared with those without a history of COVID-19, had a higher content of pro-inflammatory cytokines, in particular, IL-6, IL-8, MCP-1. In the time dynamics after complex therapy (drug and stenting of coronary arteries), there was an improvement in some indices 28 days later. In particular, in both groups (those previously ill, versus not exposed to COVID-19), the following pro-inflammatory cytokines were decreased significantly (p < 0.05): IL-6, IL-8, MCP-1, MCP-1β, TNFα. Meanwhile, the anti-inflammatory cytokine IL-10 was increased (p < 0.05). Hence, the disturbances in regulation of immunity and, first of all, in chemokine parameters, were obtained in the patients with post-COVID syndrome and ACS, in contrast to the persons with ACS who was not previously affected by COVID-19. In patients with acute coronary syndrome who have recovered from COVID-19, we have found a more pronounced disruption of cytokine regulation of immune system than in patients who did not suffer from the coronavirus infection.

Russian Journal of Immunology. 2025;28(2):321-328
pages 321-328 views

Mitochondrial uncoupling, a new element in pathogenesis of metabolic syndrome: a pilot study

Voronova S.S., Bograya M.M., Vulf M.A., Gorbacheva A.M., Gazatova N.D., Kuznetsov G.L., Litvinova L.S.

Abstract

Obesity and insulin resistance are the main factors in development of metabolic syndrome (MetS). In patients with MetS, there is an active accumulation of free fatty acids in the liver, which may lead to disturbances in homeostasis and metabolism of hepatocytes, thus resulting in mitochondrial dysfunction, oxidative stress, and cellular apoptosis. Mitochondrial dysfunction has been extensively studied in the context of pathogenetic features of metabolic syndrome. However, the processes of mitochondrial uncoupling remain unclear. Mitochondrial uncoupling (MU) is a process associated with a decrease in ATP synthesis and reactive oxygen species (ROS) in mitochondria. It is mediated by proteins from the UCP (uncoupling proteins) family, as well as ANT (ADP/ATP translocase). “Mild” MU is necessary for maintaining normal mitochondrial function, whereas “severe” MU may lead to mitochondrial dysfunction. Thus, the aim of the present study was to investigate the expression levels of SIRT1 V1 deacetylase, transcription factors PGC-1α, PPAR-α, PPAR-γ that stimulate lipogenesis and β-oxidation of FFAs, and expression of some genes encoding mitochondrial uncouplers ANT2 and UCP2 in the liver of patients with MetS. The study included two groups, as follows: patients with MetS (inclusion criteria: BMI > 30 kg/m2, along with type 2 diabetes and/or fasting blood glucose > 5.5 mmol/L), and a control group (BMI < 30 kg/m2, absence of infectious and chronic diseases). Biochemical analysis of blood parameters was conducted using the Furuno CA-180 biochemical analyzer (Furuno Electric Company, Japan) with DiaSys test systems (DiaSys Diagnostic Systems, Holzheim, Germany). The expression levels of the genes of interest in liver biopsies were assessed using quantitative RT-PCR with SYBR Green (Evrogen, Russia).

In patients with MetS, a significant increase (compared to the control group) in expression level of the PPAR-γ transcription factor was found, being associated with de novo lipogenesis in the liver, as well as increased expression of mitochondrial ANT2 uncoupler gene. Expression levels of other genes (SIRT1 V1, PGC-1α, PPAR-α, UCP2) measured in liver biopsies from the patients with MetS did not show significant changes. An increased expression of the ANT2 gene in MetS patients may be related to both compensatory protective mechanisms, e.g., activation of “mild” MU, and pathological processes resulting from “strong” MU. Further studies are needed to investigate the effects of ANT2 and UCP2 on the cellular metabolism (ATP production, ROS generation, development of oxidative stress), both directly in human liver tissue, and in cell cultures. This article presents for the first time the results concerning expression of mitochondrial uncoupler genes (ANT2, UCP2) in the liver of patients with MetS.

Russian Journal of Immunology. 2025;28(2):329-336
pages 329-336 views

C. difficile-associated enterocolitis in a child: a clinical case

Abyanova P.I., Matiyeuskaya N.V., Klyuchnik E.V.

Abstract

Antibiotic-associated diarrhea (AAD) is one of the most significant complications of antibacterial treatment. The objective of the study was to provide a clinical case of C. difficile-associated enterocolitis in a child. Case description. A clinical case of moderate enterocolitis caused by C. difficile is presented in a 4-year-old child who fell ill while taking 3 courses of antibiotics (cefotaxime, claptrithromycin, amikacin), which manifested as abdominal pain, false attempts to defecate, frequent scanty mucous stool with blood admixture, fever. At the same time, negative results were obtained from bacteriological stool culture for enteropathogenic microflora and stool testing for intestinal viruses using ELISA and PCR; a questionable result was obtained at stool testing for the type A and B C. difficile toxins. A general blood test showed neutrophilic leukocytosis and a left shift in the differential leukocyte counts, inflammatory changes in the coprogram, thickening of the colon wall up to 3-4.5 mm according to ultrasound data, enlarged mesenteric lymph nodes were found. Upon anti-infectious therapy with vancomycin and metronidazole, rapid positive dynamics of the child’s condition and recovery were noted. Conclusions. The diagnosis of C. difficile-associated infection should be established on the basis of a comprehensive analysis of available clinical, epidemiological, anamnestic, laboratory and instrumental data. Negative or questionable results of the test for C. difficile toxins A and B in feces does not exclude an infection associated with C. difficile.

Russian Journal of Immunology. 2025;28(2):337-340
pages 337-340 views


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