Russian Journal of Immunology

Peer-review quarterly medical journal.





Founded in 1996.

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

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


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Types of accepted articles

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


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



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

Posted: 19.02.2022

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

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Current Issue

Vol 25, No 4 (2022)

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Full Issue


Local immune state in the women with miscarriage
Abramovskikh O.S., Loginova Y.V.

Functional state of immunity provides maintenance of immunological tolerance for allogeneic fetus, and high level of local protection against antigenic stimulation. Increased functional activity of phagocytic cells at systemic and local levels may cause impairment of complete fetoplacental complex, thus leading to abortion. The purpose of our study was to assess the state of local immunity in women with pregnancy loss.

The study involved 174 women in their reproductive age. The first group consisted of 65 patients (37.4%) with a diagnosis of miscarriage, the history of < 2 abortions over the period from conception to the 20th week of gestation. The second group included 37 patients (21.2%) with documented recurrent pregnancy loss, with a history of > 3 miscarriages. The control group consisted of 72 conditionally healthy women (41.4%) who had 2 or more term pregnancies with the same partner, without a history of obstetric and gynecological complications. Their mean age was 36±6 years old. Total number and viability of leukocytes, the indices of functional neutrophil activity, their functional reserve and neutrophil stimulation index were determined in cervical mucosal samples over the first phase of the menstrual cycle.

In the first phase of menstrual cycle, the women with miscarriage and recurrent pregnancy loss exhibited a statistically significant increase of phagocytosis by the neutrophils from cervical mucus as compared to the group of conditionally healthy women. Intensity of neutrophil phagocytosis in cervical mucus reached higher values in the women with recurrent pregnancy loss more often, compared to the control group. Evaluation of the functional reserve of cervical mucus neutrophils in the subjects with recurrent pregnancy loss and miscarriage showed a trend towards statistically significant differences: this parameter was higher in the patients than in control group. The ability of cervical mucosal neutrophils to produce reactive oxygen species (both spontaneous and induced) did not show statistically significant differences between the patients and controls.

Hence, we have observed aberrant functional activity of neutrophilic granulocytes from cervical mucosa in the groups of women with 2 or more abortions, without changing ability of the cells to produce reactive oxygen species. This finding may be explained by prevalence of oxygen-independent mechanisms of intracellular killing, thus suggesting a role of neutrophils for impaired balance of immunological tolerance in pregnant women at the local level.

Russian Journal of Immunology. 2022;25(4):363-368
pages 363-368 views
Effect of cucurbiturils on cytokine production by peripheral blood mononuclear cells of healthy donors
Aktanova A.A., Kovalenko E.A., Pashkina E.A.

Many drug delivery systems are currently under study, e.g., nanosized cavitands cucurbiturils, which, due to the presence of a cavity, can incorporate drug molecules. Since the immune system is quite sensitive to influence of nanomaterials and other cell-damaging factors, it is necessary to study immunosafety of the new delivery systems, i.e., immunotoxicity and immunomodulatory properties. The aim of this study was to investigate the effect of nanosized cucurbituril cavitands on the cytokine-producing ability of peripheral blood mononuclear cells in apparently healthy donors.

Blood mononuclear cells (106/mL) were cultured in the presence of cucurbiturils at the following concentrations: 0.3 mM cucurbit[6]uril, 0.3 mM cucurbit[7]uril, and 0.01 mM cucurbit[8]uril for 72 h, under additional stimulation with aCD3 antibodies (1 µg/mL), or without it. The level of cytokines in the supernatants was determined using enzyme immunoassay.

It was shown that cucurbit[6]uril increased the level of spontaneous IL-4 production by 1.5 times (p < 0.01) compared with the control. In the case of stimulated cytokine production, we found that cucurbit[6]uril reduced the level of IL-6, and also shows a tendency (p = 0.09) towards an increase in the IL-4 level. When cells were cultured with cucurbit[7]uril, we gave revealed a trend for increased production of pro-inflammatory TNF. It was also found that cucurbit[7]uril is able to suppress the production of IL-10 in aCD3-stimulated cell culture by 1.5 times. Cucurbit[8]uril was shown to inhibit production of cytokines in non-stimulated cell cultures. A significant decrease in the level of IFNγ and IL-10 was revealed as compared with the production of these cytokines in control cultures. When assessing the effect of cucurbit[8]uril on the IFNγ production upon stimulation with aCD3 antibodies, no significant differences were found, but there is also a trend for a decreased concentration of this cytokine agains control levels.

Cucurbiturils can influence both spontaneous and stimulated production of cytokines by the blood mononuclear cells. The effect on cytokine-producing ability of the cells depends on the tested homologue compound.

Russian Journal of Immunology. 2022;25(4):369-374
pages 369-374 views
Prognosis of COVID-19 outcomes and risk prediction for the development of post-COVID syndrome
Atazhakhova M.G., Chudilova G.A., Nesterova I.V.

At the present time, the new laboratory diagnostic markers are required which may predict complications over the post-COVID period, as well as improve diagnostics of post-COVID syndrome in the patients who underwent COVID-19. Despite the fact that changes in respiratory system are the most common manifestations of COVID-19, extrapulmonary manifestations followed by the wide range of persistent symptoms and/or delayed complications may lead to multiple organ lesions of varying severity: from symptomless to fatal forms. A number of symptoms in the developed post-COVID syndrome may persist for > 3 weeks, or to be prolonged up to 6 months and later. The purpose of the study was to investigate the informativity of an early integrative diagnostic index developed by us, enabling prediction of the COVID-19 outcome, and potential development of early post-COVID syndrome.

Peripheral blood samples were examined in 60 patients (38-82 years old) diagnosed with COVID-19 of moderate severity (CT-2.3) during their inpatient treatment; 30 patients (38-62 years old) in the early post-COVID period and 34 patients (38-65 years old) with early post-COVID syndrome. The comparison group consisted of 100 healthy sex- and age-matched volunteers. The IDP, an integrative diagnostic index, was calculated as a marker including the ratio of the relative neutrophil-to-lymphocyte numbers, as well as the levels of C-reactive protein (CRP), by the following formule: IDP = (% neutrophilic granulocytes × CRP) / % lymphocytes.

We have found that, during the inpatient treatment, upon acute clinical manifestations, IDP in study group 1 was increased 12.5 times against the comparison group. It should be noted that all patients were discharged from the hospital in compliance with official criteria, according to Temporary Guidelines. In the study group 2, during early postcovid period, IDP remained 3.4-fold elevated against the comparison group. According to the chest CT data, the patients had signs of a fibrous component, organizing stage of pneumonia and consolidation foci in the lung tissue. Among the group 3 patients (early post-COVID syndrome), IDP was increased three-fold against the comparison group, accompanied by the documented signs of chronic fatigue syndrome and cognitive impairment.

The IDP can be used as a marker for the prognosis of clinical outcome and a predictor of the evolving complications during the early post-COVID period and upon development of early post-COVID syndrome in the patients who have undergone COVID-19.

Russian Journal of Immunology. 2022;25(4):375-378
pages 375-378 views
Gastrointestinal manifestations of allergy in the presence of Helicobacter pylori infection
Barilo A.A., Smirnova S.V., Feizer A.A.

Association of Helicobacter pylori infection with gastrointestinal tract disorders is one of the most common problems in the modern medicine. There are conflicting data in the literature on the role of H. pylori infection in development of allergic diseases and its effect on the course of gastrointestinal disorders in allergic conditions. There is currently no conclusive evidence about the role of H. pylori in etiology and pathogenesis of allergic states. Hence, the studies of gastrointestinal disorders in allergic conditions in the presence of H. pylori infection are of sufficient relevance. Our aim was to study the features of sensitization spectrum and clinical course of gastrointestinal manifestations in allergic disorders in the children infected with H. pylori.

We have carried out a retrospective analysis of medical histories of the children with gastrointestinal manifestations of allergies (n = 29) aged from 1 to 18 years (middle age, 11±0.7 years), living in Eastern Siberia. The presence of H. pylori infection was determined with enzyme immunoassay technique, by measuring concentrations of total antibodies to the CagA H. pylori antigen. Depending on the carriage of H. pylori infection, 2 groups were discerned: HP-infected (n = 8), and HP-non-infected patients (n = 21). The spectrum of sensitization was determined by evaluating skin-prick tests for the non-infectious allergens. Gastrointestinal tract evaluation was based on the results of anamnesis, complaints, objective examination and data of esophagogastroduodenoscopy.

It was found that, in most cases, gastrointestinal manifestations of allergy were combined with dermatorespiratory syndrome (41.3% of total group). The incidence of H. pylori infection in the patients with gastrointestinal manifestations of allergies was 27.5% of the group. Among the gastrointestinal manifestations of allergies, inflammatory diseases of the esophagus, stomach, and intestines, e.g., gastroesophageal reflux, gastritis, and duodenitis were most common. In the group of HP-infected children the incompetence of cardia was more often, being statistically significant. In the group of HP-noninfected children, esophagitis, bulbitis, erosive lesions of the stomach and duodenum were more common, however, the difference did not reach statistical significance. The spectrum of sensitization in the patients with gastrointestinal manifestations of allergies showed some features depending on the presence of HP infection. E.g., sensitization to birch and meadow grass mixture was found to be significantly more often in the group of HP-infected children, Among the HP-noninfected children, sensitization to house dust mite, cat wool, and dog wool was more often detected. Hence, when examining children with gastrointestinal manifestations of allergies it is necessary to exclude the presence of H. pylori infection, which can modify the course of a genuine allergic pathology.


Russian Journal of Immunology. 2022;25(4):379-384
pages 379-384 views
Content of PD-1+ and PD-L1+ peripheral blood lymphocytes in individuals with pollen sensitization before and after allergen-specific immunotherapy
Barkovskaya M.S., Sevastyanov P.V., Demina D.V., Kozlov V.A.

The available data on the contribution of the PD-1 and its ligands to immunoregulatory processes suggest their involvement into development of tolerance during immunotherapy. Currently, allergen-specific immunotherapy (ASIT) is the single treatment option that can influence the outcome of allergic diseases. Our purpose was to evaluate the PD-1/PD-L1 expression on the immune cells in patients with confirmed sensitization to plant pollen allergens in comparison with healthy controls before and after ASIT. The patients with bronchial asthma (BA) (n = 5, age 33.8±2.7), allergic rhinitis (AR) (n = 7, age 31.6±2.8), and healthy donors (n = 12, age 32.8±1.8) were included. Venous blood samples were obtained from the patients three times: before starting ASIT, upon completion of the ASIT course, and during the period of seasonal exacerbation. In patients with AR, the number of B lymphocytes was decreased, and the expression of PD-L1 by B lymphocytes increased after ASIT in comparison with donor parameters. At the same time, B lymphocyte counts were increased in BA patients before ASIT and returned to normal after ASIT. In AR, the CD8+PD-1+T lymphocyte count was reduced before ASIT, however, returning to normal values after ASIT was completed. Meanwhile, the reduced number of CD4+PD-1+T lymphocytes returned to normal only during the pollination season following ASIT. In BA patients, both before or after ASIT, PD-1 and PD-L1 expression on CD4+ and CD8+T lymphocytes did not differ from the donor parameters. The PD-1 expression in the T regulatory cells (Tregs) was decreased comparing with donors before ASIT in BA, and in the patients with AR, both before and after treatment. It was shown earlier that low PD-1 expression in the circulating CD4+ T cells is associated with high specific IgE concentrations. Thus, low PD-1 levels on CD4+ and CD8+T lymphocytes and regulatory T cells may indicate their functional disorders in allergic pathology. In summary, our results show a regulatory role of PD-1/PD-L1 axis in the immune response during ASIT and reflect differences in pathogenesis of allergic disorders, which are associated with imbalance of the cell activation and suppression. Further studies are required to establish the role of PD-1/PD-L1 interactions in the process of ASIT-induced modification of allergic responses.

Russian Journal of Immunology. 2022;25(4):385-392
pages 385-392 views
Phenotypic features of innate lymphoid cells in rheumatoid arthritis
Boeva O.S., Berishvili M.T., Sizikov A.E., Pashkina E.A.

Currently, rheumatoid arthritis (RA) is considered among the most common autoimmune diseases worldwide, being associated with progressing disability, systemic organ and tissue lesions, as well as social and economic losses for the state. Studies of innate lymphoid cells (ILS) seems to be actual and significant when studying development of autoimmune inflammation in RA, in particular, the issues of the cell plasticity. ILC represent tissue resident lymphoid cells that display functional diversity, like as T cells. Moreover, ILC regulate orientation of immune response by means of cytokine production. Small amounts of ILCs are present in the bloodstream, presumably for migration to target organs and tissues. Accordingly, the study of ILC in RA will promote understanding of the RA pathogenesis. It is also possible in the future to develop new therapeutic strategies based on the impact on the immunological balance, as well as reducing the inflammatory process in RA. The aim of this study was to determine the subpopulation composition and phenotypic features of ILCs in RA.

We have isolated and studied peripheral blood mononuclear cells (PBMC) from 7 patients with RA and 6 healthy donors. The isolated blood MNCs were stained with monoclonal antibodies conjugated to fluorochromes: lineage-specific (CD3/14/16/19/20/56) and anti-FceR1 alpha-FITC, anti-CD294-APC/Cy7, anti-CD127-PerCP/Cy5.5, anti-CD336-PE, anti-CD117-APC. ILCs were defined as Lin-CD127+. The numbers of CD294+ILCs (ILC2) were estimated in the general population, CD117-CD294-ILCs were defined as ILC1, and CD117+CD294-ILCs, as ILC3. The cell phenotype was analyzed with a FACS Canto II flow cytometer (BD Biosciences, USA).

We determined relative numbers of different ILC subpopulations (ILC1, ILC2, and ILC3) among the total blood MNCs. It was shown, that the number of ILC2 cells in RA patients was statistically significantly reduced compared to healthy donors, whereas no significant differences in percentage of ILC1 and ILC3 were revealed between donors and patients. We also evaluated the amount of c-Kit+ILC2; there were no significant differences in the proportion of these cells between donors and patients.

ILCs represent a population of cells that contribute to the RA pathogenesis. The role of ILC2 in RA is, presumably, protective. The ILC imbalance may contribute to the development of RA. For a better understanding of the RA pathogenesis, further studies of the subpopulation profile, phenotypic and functional characteristics of ILC are required in this disorder.

Russian Journal of Immunology. 2022;25(4):393-398
pages 393-398 views
MicroRNA signature of leukocytes in the context of chronic systemic inflammation in vascular dementia
Burmistrova A.L., Alekseeva A.S., Cazaux M.E., Filippova Y.Y.

Chronic low-level inflammation during the aging process is a key risk factor for the activation of resident cells of the brain innate immune system of the (microglia and astrocytes). Such activation leads to the development of neuroinflammation and cognitive impairment which are typical to neurodegenerative diseases such as Alzheimer’s disease, vascular dementia, Parkinson disease etc. Currently, there is a lack of minimally invasive, affordable methods for diagnosing age-related neurodegenerative diseases and drugs that could slow down or prevent their progression. Hence, a search for new peripheral biomarkers is required, both for diagnostics and monitoring the efficiency of drug therapy. The option of using microRNAs as such biomarkers is under discussion. Our goal was to identify a leukocyte microRNA signature in vascular dementia as compared with healthy aging and reproductive age, in view of inflammation and cognitive deficits. We have examined 54 persons from young to senile age who were classified into the following groups: “Vascular dementia”, “Healthy aging” and “Reproductive age”. Expression of miRNAs known as regulators of communications between the immune and nervous systems (let-7d, let-7g, miR-21, miR-124, miR-146a, miR-155, miR-342-3p) was measured in peripheral blood leukocytes. The decision to study leukocytes was made, since these blood cells are responsible for immune functions, and, especially, cytokine production during aging. Total RNA was isolated by phenol-chloroform technique. The microRNA expression was determined by quantitative polymerase chain reaction with SYBRGreen. The U6 gene of small nuclear DNA was used as a reference “housekeeping” gene. The differences between groups were determined using the Kruskal–Wallis test with post hoc pairwise comparisons according to Conover–Inman. As a result of the study, it was found that the expression of microRNA-21 and microRNA-342 in leukocytes of elderly/senile people, both in healthy aging and in vascular dementia, was increased when compared to the persons in their reproductive age. In the persons with vascular dementia, the expression level of miRNA-124 and miRNA-342 in peripheral blood leukocytes was higher than in healthy aging group. Hence,, microRNA-124 and microRNA-342 may be informative biomarkers for the diagnostics of vascular dementia. However, large-scale studies of their biomarker potential are warranted.

Russian Journal of Immunology. 2022;25(4):399-404
pages 399-404 views
HBD1 and LL37 gene expression in children with atopic dermatitis
Bystritskaya E.P., Murashkin N.N., Materikin A.I., Naumova E.A., Yakovleva I.V., Vartanova N.O., Svitich O.A.

Atopic dermatitis (AD) is a multifactorial genetically determined inflammatory skin disease characterized by itching, chronic course, age-related features of localization and lesion morphology. Atopic dermatitis is caused by complex interactions between genetic, immunological, and environmental factors. The barrier function of the skin is impaired in atopic dermatitis. Antimicrobial peptides, e.g., LL-37, b-defensins are involved in maintaining the skin barrier function (especially, intercellular contacts). An imbalance of antimicrobial peptides may cause different disorders, including allergic pathologies. The aim of this study is to investigate gene expression profile of the HBD1 and LL37 encoding antimicrobial peptides in the samples of skin and blood mononuclear cells obtained from the children with moderate and severe atopic dermatitis before and after treatment. By means of real-time polymerase chain reaction, the levels of HBD1 and LL37 gene expression were evaluated in the samples. Statistical analysis showed significantly increased (p ≤ 0.017) expression levels of both HBD1 (H-test = 24.76; 2, n = 72; p = 0.00001), and LL37 genes (H-test = 15.69; 2, n = 72; p = 0.00039) in blood cells of AD patients compared to the control group, as well as decreased (p ≤ 0.05) levels of HBD1 expression in the affected skin compared to the control group. Our data on the cathelicidin gene in the skin do not differ from the literature data, since its expression is reduced in AD. In our series, an increase of the gene expression was revealed in PBMCs. The HBD1 peptide is expressed in both monocytes and macrophages, representing a link between innate and adaptive immunity. In our study, the expression of the HBD1 gene was increased only in blood, thus suggesting activation of innate immunity components at the systemic level in response to inflammation. Of importance, understanding the role of immunological markers in AD will help to develop novel prognostic approaches in management of the patients with atopic disorders. Therefore, one should understand pathogenetic mechanisms of allergic diseases.

Russian Journal of Immunology. 2022;25(4):405-410
pages 405-410 views
Increase of blood neuregulin 4 is associated with type 2 diabetes mellitus and hypertension in obese patients
Vulf M.A., Safiullina L.A., Gazatova N.D., Kuznetsov G.L., Komar A.A., Kirienkova E.V., Litvinova L.S.

Obesity and type 2 diabetes mellitus (T2DM) are global epidemics at the present time, being a serious public health issue. An increased prevalence in the number of obese people promotes a risk for developing cardiovascular diseases (CVD) and some types of cancer. The ErbB signaling pathway plays a significant role in development of the disorders associated with metabolic dysfunction (e.g., T2DM, obesity, arterial hypertension). Neuregulin 4 (NRG4) is a new adipokine with similar effects to adiponectin. Interaction between the ErbB3, ErbB4 receptors and their ligand, NRG4, launches the processes required to maintain the energy balance in the cells. There are controversial literature data on NRG4 levels in blood circulation. In particular, the existing data concerning functions / mechanism of NRG4 action has been obtained in experimental animals and cell lines, which is not always reproducible in humans. According to some works, liver may be the key target organ for NRG4. The present article is devoted to assessment of relationships between the NRG4 level in blood, and the parameters of carbohydrate and lipid metabolism, as well as presence of diseases associated with obesity. The study included obese patients with and without type 2 diabetes. The content of NRG4, indices of carbohydrate and lipid metabolism in the blood was assessed by means of enzyme immunoassay and biochemical techniques, respectively. It was found that the level of NRG4 was increased in obese patients with T2DM compared with healthy donors, and obese patients without T2DM. Statistical evaluation by correlation and regression analysis revealed numerous relationships between NRG4 and the parameters of lipid and carbohydrate metabolism, as well as some correlations between the NRG4 levels and clinical disorders associated with obesity (type 2 diabetes and arterial hypertension). Thus, NRG4 may be involved into the development of dyslipidemia in obese patients. We consider an increase of blood NRG4 levels in obese patients with type 2 diabetes as a compensatory response to the increased insulin-mediated lipogenesis. The data obtained are important in search for new points of influence upon pathogenesis of diseases associated with metabolic disorders. Neuroregulin 4 and its receptors may be promising targets for the treatment of socially significant clinical disorders.

Russian Journal of Immunology. 2022;25(4):411-418
pages 411-418 views
Population immunity in residents of the Kaliningrad region to current antigenic variants of influenza viruses over 2018-2021
Goncharov A.G., Egorenkova O.A., Shupletsova V.V.

The article presents the results of population immunity assessment in residents of the Kaliningrad region to current antigenic variants of influenza viruses over the period of 2018 to 2021. To assess spectrum of influenza types circulating in Kaliningrad region, the real-time PCR method was used using AmpliSense reagent kits. The biological material for the study was obtained from oropharyngeal swabs from the persons who applied to polyclinics with inflammatory diseases of upper respiratory tract, or underwent treatment at the out- or inpatient basis in a healthcare facilities of Kaliningrad region. Humoral immunity was assessed by testing blood sera obtained from healthy residents of Kaliningrad region during periodic prophylactic examinations at the city and regional polyclinics. The study of residents covered all age groups. For the period of 2018-2021, more than 14,000 studies have been carried out. Determination of specific serum antibody titers was carried out by staging the hemagglutination suppression reaction using local influenza antigens (LLC «PPDP», St. Petersburg). Antibody titers of 1/40 and higher were considered sufficient to reduce the risk of disease by > 50%. During the study period, 2165 cases of influenza were confirmed in the region by laboratory tests. Over the study period, the A(H1N1) pdm serotype proved to be the major strain causing influenza, its proportion reached 57.5%. However, along with A(H1N1) pdm, a significant contribution was also made the A(H3N2) strain to the epidemic process, being the etiological cause of influenza infection in 2019 (42.2%), type B influenza strains being actual in 2020 (42.5%). Over the period of 2018-2021, 420 samples of blood sera from vaccinated and non-vaccinated individuals were tested for specific antibodies. The sera were taken 1-2 months after vaccination and between epidemic rises of influenza (April-May). In vaccinated individuals, the antibody titer was protective in 58.3-64.5%. In this group of persons, the titer sufficient to produce immunity was maintained over the spring/summer period. Among those persons who refused vaccination, a protective antibody titer in the pre-epidemic period was noted in 41.2% of the examined, and during the off-season it was detected in 37.4% of the volunteers. Thus, the A(H1N1) pdm strain was the main etiological factor of influenza in Kaliningrad Region in 2018-2021. The protective level of antibodies in vaccinated population over the period preceding the epidemic peak, was observed 30% more often than in unvaccinated individuals. High incidence of influenza B strains noted in 2020 appears to require a change of specific vaccine preparation.

Russian Journal of Immunology. 2022;25(4):419-422
pages 419-422 views
Dynamics of cell-free DNA levels in the in vivo LPS-induced inflammation model
Demchenko E.N., Gavrilova E.D., Goiman E.V., Volskiy N.N., Kozlov V.A.

An increased concentration of extracellular cell free DNA (cfDNA) is a distinctive characteristic of pathologies that mainly occur in acute inflammation (myocardial infarction, sepsis, stroke, trauma). The increase of cfDNA in chronic inflammatory processes, oncological, autoimmune diseases is less significant and is mainly due to aberrant cell death processes. One of such diseases is systemic lupus erythematosus (SLE). It has recently been shown that, in addition to increased cfDNA concentration, the degree of inflammation can reflect the N/L index (neutrophil to lymphocyte ratio), being a simple and informative marker of disease activity in patients with SLE. The aim of the study was to study the dynamics of the level of cfDNA and the N/L index in the model of LPS-induced inflammatory response as observed in intact mice, and their relation to the phenotypic heterogeneity of model SLE. We used female hybrid mice (C57Bl/6xDBA/2) F1 and female DBA/2 mice at the age of 6-8 weeks. LPS of E. coli strain 111: B4 (Sigma) was injected intraperitoneally once at doses of 10 ng, 1 µg and 100 µg per mouse in PBS. The control group was injected with the appropriate volume of buffer. The TNFα-binding domain of the variola virus CRMB protein was used as an inhibitor of TNFα, which was administered 30 min before the introduction of LPS. The dynamics of the response to LPS was assessed after 4, 8, 11, 24 hours by the N/L index and the level of cfDNA; at the zero point, the parameters were determined before the introduction of LPS. A day after a single injection of LPS at a dose of 1 µg/mouse, a SLE model was induced on the same hybrid mice (double intravenous administration with an interval of 6 days of spleen cells of the DBA/2 line, 60-70 × 106 cells each). Three months later, with proteinuria of 3 mg/ mL or more, mice were assigned to the SLEnephritis+ group, with a protein of less than 3 mg/mL, to the SLEnephritis- group. Statistical processing of the results was carried out by nonparametric statistics using the Mann–Whitney test. Differences were considered statistically significant at p < 0.05. It was found that the change in the N/L index, as well as the change in the level of cfDNA, depends on the dose of LPS administered. It was shown that the level of cfDNA reaches its maximum after 8 and 11 hours after the introduction of LPS is reliably reduced when using the inhibitor TNFα. A retrospective analysis indicates that there is a definite relationship between the response of intact mice to LPS before induction of cGVHD, and their subsequent division into variants of SLEnephritis + and SLEnephritis - in the course of disease development.

Russian Journal of Immunology. 2022;25(4):423-430
pages 423-430 views
Studies of CD45+ and CD46+ expression on the peripheral blood lymphocyte subsets of the post-COVID patients
Dobrynina M.A., Zurochka A.V., Komelkova M.V., Luo S., Zurochka V.A., Desheng H., Ryabova L.V., Sarapultsev A.P.

The SARS-CoV-2 virus can enter the cells using S1 viral spike (S) protein, not only by binding to ACE2, but also through other cellular receptors. These candidate receptors include CD46, which, like CD45, belongs to pan-leukocyte receptors and is expressed on all types of lymphocytes. In turn, SARS-CoV-2 infection is accompanied by damage to almost all compartments of the immune system, mainly T lymphocytes. The purpose of the study was to evaluate the expression levels of CD45+ and CD46+ in various subpopulations of lymphocytes in patients who had undergone SARS-CoV-2 infection.

72 patients who had undergone SARS-CoV-2 infection were examined. Using flow cytometry technique, we determined CD45+ and CD46+ (panleukocyte marker for lymphocyte gating), CD45+ and CD46+, CD3+ (T lymphocytes), CD45+ and CD46+, CD3+, CD4+ (helper inducers), CD45+ and CD46+, CD3+, CD8+ (cytotoxic T-lymphocytes), CD45+ and CD46+, CD3+, CD56+ (TNK cells) CD45+ and CD46+, CD3-, CD56+ (natural killers), CD45+ and CD46+, CD3-, CD19+ (B lymphocytes), CD45+ and CD46+, CD3+, CD4+, CD25+ (activated helpers, early activation of lymphocytes), CD45+ and CD46+, CD3+, HLA-DR (activated T lymphocytes – late activation of lymphocytes). Our studies have shown that a decrease in CD46+ expression in T lymphocytes (CD3+) is accompanied by similar decrease of its expression in cytotoxic T lymphocytes (CD3+, CD8+), TNK (CD3+, CD56+), as well as in helpers T carrying markers of early activation (CD3+, CD4+, CD25+). At the same time, the most pronounced decrease was observed both among total T lymphocytes and cytotoxic T cells. In these patients, the expression level of CD46+ in B lymphocytes was slightly increased. Recent data suggest that there is no involvement of CD46 receptor on B lymphocytes. Our data suggest that the SARS-CoV-2 virus may affect the CD46 receptor. Such exposure may lead to promotion of the long-COVID (post-COVID) symptoms in such patients, thus requiring new approaches to correction of these disorders.

Russian Journal of Immunology. 2022;25(4):431-436
pages 431-436 views
Relationships between the factors of innate immune system and results of neurocognitive function parameters in the persons living with HIV infection: interim results of the study
Knysh S.V., Sklyar L.F., Cherkasova Y.S., Chernikova A.A., Knysh A.A., Nevezhkina T.A., Chagina E.A.

HIV infection is closely associated with damage to the nervous system, even despite usage of antiretroviral therapy. Thus, the patients are at a high risk for neurological complications. Due to limited permeability of the blood-brain barrier, the opportunity of its damage, both directly by the proteins of HIV-infected cells and indirectly, by immune system, e.g., inducing the production of inflammatory mediators, the involvement of the central nervous system in pathogenesis of HIV infection seems to be only a matter of time. HIV-associated neurocognitive disorders (HAND) comprise a poly-etiological pathological condition associated with direct and indirect damage to neurons in HIV infection. The role of interaction between the innate immune system and nervous system mediators in viral infections suggests that the specific changes in content and ratios of pro- and anti-inflammatory cytokines that are among the most polypotent mediators of immune regulation can be detectable in the persons prone to the development of HAND in HIV infection. The purpose of the present study was to characterize the features of serum content and the relationship between the indexes of innate immunity factors with the results of neurocognitive testing in the persons living with HIV.

123 persons were included in the study, of which 93 subjects live with HIV infection. They were divided into 3 groups according to the stages of HIV infection, according to the Russian Classification of HIV infection. 30 persons represented a group of healthy volunteers, comparable in age and gender with the members of main groups, and served as a control group. Determination of IL-1β and IL-10 contents in blood serum was carried out by solid-phase enzyme immunoassay. The level of CD4+T lymphocytes was determined by flow cytometry. Neurocognitive testing using Schulte tables, the Munsterberg test was conducted by a medical psychologist, according to generally accepted methods.

A significant increase in the serum IL-10 content in subjects from the main groups was revealed as compared with the control group, as well as in group III compared with the values groups I and II. The levels of IL- 1β, CD4+T lymphocytes were significantly lower in group III, compared with all other groups. The personal performance index determined by testing with Schulte tables was reduced in all groups, relative to the controls, with a significant predominance of the results in groups I and II over the results of the participants from group III. The scores in Munsterberg test were equally diminished in all the main groups compared to the control values. When assessing the Spearman coefficient, the presence of various correlation profiles was established, depending on the stage of the disease.

Russian Journal of Immunology. 2022;25(4):437-444
pages 437-444 views
Experimental in vitro reprogramming of transformed phenotype of neutrophil granulocyte subpopulations in women with chronic recurrent infectious and inflammatory conditions of genital tract
Kovaleva S.V., Pikturno S.N., Chudilova G.A., Lomtatidze L.V., Krutova V.A., Malinovskaya V.V., Nesterova I.V.

Chronic inflammatory diseases of the pelvic organs (CIDPO) in women represent one of the urgent and insufficiently studied problems in gynecology across the world. These disorders are followed by adverse medical and socio-economic consequences, i.e., chronic local inflammatory process, chronic pelvic pain syndrome, ectopic pregnancy, infertility. Due to increasing chronicity and recurrence rates of genital infections and inflammatory diseases, there is a need for further studying the effector and regulatory mechanisms of immune system. Of special relevance are the studies of the receptor transformation in neutrophilic granulocytes (NG), the basic population of antimicrobial defense, with further substantiation of targeted immunomodulatory therapy. Purpose of the present study was to assess transformation of neutrophilic granulocytes from CD11b+CD64-CD32+CD16+ to that CD11b+CD64+CD32+CD16+ phenotype in immunocompromised women with CIDPO exacerbation, as well as to evaluate the possibility of in vitro reprogramming the neutrophile phenotype under the action of recombinant interferon (recIFNα2b). Peripheral blood neutrophils were tested in the comparison group of 10 conditionally healthy women 20 to 40 years old, and in 17 women (20-40 years old) with the CIDPO exacerbation (group 1). The in vitro effect of recIFNa2b on the blood neutrophils was evaluated for 17 women with CIDPO (group 2). Flow cytometric technique (FCT, CYTOMICS FC500, Beckman Coulter, USA) was used to determine the number of NGs and cell receptor expression levels of neutrophilic CD11b+CD64-CD32+CD16+NG and CD11b+CD64+CD32+CD16+ subpopulations. In peripheral blood of women with CIDPO exacerbation, an increased expression density of surface membrane molecules was revealed by means of FCT: in the subpopulation CD11b+CD64-CD32+CD16+NG, CD16 proved to be 91.7% higher; in CD11b+CD64+CD32+CD16+NG subpopulation, CD16 was increased by 116%, and CD32 being higher by 81% against the comparison group. In the in vitro system, during the incubation of PB with recIFNα2b (group 2), we have revealed an increased number of CD11b+CD64-CD32+CD16+ subpopulation relative to the comparison group and group 1, and significantly increased expression density of CD16 (by 212%); CD11b (by 56%), and CD32 (by 83%) than in comparison group, as well as higher density of CD16 expression by 163%; CD11b (by 223%) compared to group 1. The changes in expression density of membrane molecules was also detected by FCT for the activated subpopulation CD11b+CD64+CD32+CD16+NG, i.e., an increase in CD16 by 232% against control group, and decreased expression density of CD64 by 150% against the background, along with increased density of CD16 expression (by 54%), and CD11b (by 103%), relative to group 1, thus suggesting a reprogramming of negatively transformed NC phenotype. These findings may be considered a positive immunomodulatory effect providing a basis for further research in order to develop new integrated approaches to treatment of CIDPO of various etiologies.

Russian Journal of Immunology. 2022;25(4):445-452
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Features of immune status in children with Wilson–Konovalov disease at different stages of liver fibrosis
Kurbatova O.V., Kuptsova D.G., Bezrukavnikova L.M., Radygina T.V., Movsisyan G.B., Anushenko A.O., Komarova A.D., Potapov A.S., Petrichuk S.V., Fisenko A.P.

The pathology in Wilson–Conovalov disease (WCD) results from impaired excretion of copper, thus leading to its excessive accumulation in tissues. Hypercupreniluria is characteristic to the WCD. Toxic effects of copper on liver tissue can manifest as fatty degeneration of hepatocytes, hepatitis, fibrosis and cirrhosis. Purpose of the present work was as follows: estimation of immune status in children with WD depending on the stage of liver fibrosis. Fifty-three patients with WCD aged 6 to 18 years, were examined. The stage of liver fibrosis was assessed by transient liver elastography using FibroScan F502 (EchoSence, France). The immune status of peripheral blood lymphocytes was examined using CYTOMICS FC500 flow cytofluorimeter (Beckman Coulter, USA). The relative numbers of B lymphocytes (B1 and B2 populations), NK cells, T helper cells, cytotoxic T lymphocytes, Th17 lymphocytes, regulatory T cells, activated T helper cells were assessed in the lymphoid area. All indices of the patients’ immune status were recalculated for percentage of deviation from the age-dependent reference values. Mass concentration of copper in daily urine was determined by atomic absorption method using “AAnalyst 800” spectrometer. Statistical processing was performed by Statistica10.0 program. The WCD patients are characterized by an increase of Т helpers, regulatory Т cells, Th17 lymphocytes and activated Т helpers, along with decrease of cytotoxic Т lymphocytes and NK cells against normal levels. The number of B cells did not depend on the stage of liver fibrosis and was at the lower limit of normal range, or decreased. Upon increase of the liver fibrosis stage, the number of B1 lymphocytes increases and B2 lymphocytes become decreased. The urinary copper content in the examined patients varied from 19 to 835 μg/day, being higher than the reference values in 88% of children, with median value of 175 µg/day (71-330). A correlation between urinary copper concentration and degree of immune status deviation was revealed (R = 0.63): urinary copper concentration was increased when the number of Th17 lymphocytes, B1 lymphocytes and regulatory T cells became higher, and when the number of B2 lymphocytes decreased. A significant decrease in the population of cytotoxic T lymphocytes (p = 0.034) was observed in children with WCD in the presence of Kaiser–Fleischer ring. Indexes of cellular immunity in children with WCD are an informative tool to assess the severity of liver damage.

Russian Journal of Immunology. 2022;25(4):453-460
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Complicated ways of diagnosing common variable immune deficiency (case report)
Moskalets O.V.

Common variable immunodeficiency (CVID) is one of the most frequent forms of primary immunodeficiencies with predominant antibody deficiency. Unlike most other primary immunodeficiencies, this variant often manifests in adults thus creating certain difficulties in its detection. Manifestations of common variable immune deficiency are very diverse: infectious syndrome (respiratory tract infections, septic arthritis), diarrheal clinical pattern of both infectious and non-infectious genesis, autoimmune syndrome (autoimmune cytopenias, systemic rheumatic diseases), lymphoproliferative syndrome (benign lymphoid proliferation, lymphomas), interstitial lung disease and sarcoidosis-like granulomatous changes are quite common. Due to the lack of a distinct clinical pattern, the common variable immunodeficiency is often diagnosed too late. Such patients are observed for a long time by various specialists, and the absence of pathogenetic therapy (intravenous immunoglobulins) leads to steady progression of the disease and, often, to lethal outcome. The article presents a clinical observation illustrating the difficulties in making this diagnosis. A woman hospitalized with pneumonia presented with a mass in colonic submucosa. After excluding tuberculosis and lymphoma, a diagnosis of colon lipoma was made on the basis of histological examination. A few years later, the patient’s submandibular lymph nodes were periodically enlarged. Upon repeated histological examination, the diagnosis of granulomatous necrotizing lymphadenitis was established, the patient was referred to a rheumatologist to rule out systemic vasculitis. This diagnosis was not confirmed, but further examination revealed a sharp decrease in the gamma fraction of serum proteins. Therefore, an immunologist’s counseling was recommended to rule out immunodeficiency. The following blood serum analysis revealed an extremely low IgG and IgM content, with absence of detectable immunoglobulin A. On the basis of these findings, the diagnosis of common variable immune deficiency was made for the first time. Replacement therapy with high-dose intravenous immunoglobulins with control of pre-transfusion Ig levels was recommended, with further transition to a supporting treatment schedule. Hence, one may state that general practitioners are still poorly aware of primary immunodeficiencies, especially if non-infectious manifestations dominating in the clinical pattern. Routine analysis of total protein content and protein fractions can provide information that allows to suspect deficiency of antibodies and, therefore, to assess contents of distinct serum immunoglobulins in order to confirm CVID diagnosis.

Russian Journal of Immunology. 2022;25(4):461-464
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Experimental in vitro phenotype reprogramming of two subsets of neutrophilic granulocytes in children with acute destructive pneumonia by means of a synthetic hexapeptide
Nesterova I.V., Chapurina V.N., Chudilova G.A., Tarakanov V.A.

Effector dysfunctions of neutrophil granulocytes are often associated with the occurrence of dysregulatory processes in the antibacterial immune defense. Acute destructive pneumonia is a severe purulent-inflammatory disease associated with discordant functions of effector mechanisms of neutrophil granulocytes and emergence of negatively transformed cell subsets. Therefore, the search for new experimental approaches aimed at re-orientation of negatively altered phenotype of distinct subsets of neutrophilic granulocytes in the children with acute destructive pneumonia by means of various immunotropic substances is quite relevant. The aim of the study was to evaluate the modulating effects of synthetic hexapeptide (Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine) on the contents and phenotype of 2 functionally significant subsets of major (CD16+CD64-CD32+CD11b+) and minor (CD16+CD64+CD32+CD11b+) subpopulations of neutrophils in a «closed in vitro experimental system» sampled in the children with atypical acute destructive pneumonia. We have examined twenty peripheral blood samples from 10 children with acute destructive pneumonia, and 40 blood samples of 20 healthy children 2-4 years old. Immunophenotyping of neutrophil granulocytes classified in 2 subsets was performed on the basis of expression density of membrane receptors, according to MFI criteria. Phenotypic features of neutrophil granulocyte subsets were evaluated in the in vitro system before and after incubation of peripheral blood with Hexapeptide (10-6 g/L; 37 °C, 60 min). In children with acute destructive pneumonia, compared with conditionally healthy children, the following variants of negative transformation of the neutrophil subsets were established: a significant decrease in the ratios of the major subset, i.e., from 98.0 (96.9-98.7) % o 55.8 (35.3-74.8) %, with a decreased CD16 and CD11b density expression according to MFI, and a significantly increase ratio of the minor neutrophil subset: from 1.3 (0.4-1.6) % to 52.6 (41.8-54.9) %, with increased expression of CD11b receptor, and a decrease in CD64 expression. Immunomodulatory effects of Hexapeptide upon neutrophil granulocytes of children with acute destructive pneumonia have been demonstrated in the closed in vitro system showing positive phenotype remodeling of both cell subsets in the absence of significant quantitative changes. Thus, upon treatment with the hexapeptide, we have found a significantly increased expression of activation receptors CD16, CD11b in the major subset, and a significant decrease in their expression for the minor subset to the levels typical to healthy children. At the same time, hexapeptide did not affect the studied subsets of neutrophils from healthy children, except of increased CD64 expression in the minor subset. The obtained data can be used in future to develop new approaches to the targeted immunotherapy aimed at correcting the phenotype of neutrophil granulocyte subsets in acute destructive pneumonia in children.

Russian Journal of Immunology. 2022;25(4):465-470
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Features of humoral immunity in patients with mild traumatic brain injury
Norka A.O., Vorobyev S.V., Kuznetsova R.N., Serebriakova M.K., Kudryavtsev I.V., Kovalenko S.N., Monashenko D.N., Korobova Z.R.

Traumatic brain injury (TBI) is an important problem of the healthcare system. A lPeading role in pathogenesis belongs to the action of shock wave upon skull and brain integuments, extending from the impacted site, as well as displacement and rotation of the cerebral hemispheres relative to the fixed brain stem. As a result, a cascade of metabolic, biochemical and inflammatory changes is initiated, leading to secondary damage. TBI, depending on its mechanism, severity and type, causes various primary structural and functional brain lesions at molecular, cellular, tissue and organ levels with dysregulation of all systems in the body, dependent on its degree and extent. In most cases, the brain injury increases the risk of developing epilepsy and neurodegenerative diseases such as Alzheimer’s disease, arkinson’s disease and chronic traumatic encephalopathy (CTE), with mental health disorders. TBI is a long-term symptomatic process in patients with functional and structural damage. In response to a traumatic event, the damage-associated molecular patterns (DAMPs) encountered upon tissue damage are expressed, which cause activation of the resident brain tissue cells, and secretion of multiple chemokine and cytokine by distinct cell populations. Neutrophils migrate to focal lesions, which remove damaged cells and debris. Migration of T and B cells is observed 3-7 days after the trauma. Hence, following primary injury, due to a cascade of immune reactions, a more extensive lesion, the so-called secondary trauma, is developed. The aim of our study was to evaluate the role of immune response in pathogenesis of mild traumatic brain injury.

An increased number of Bm2 cells, IgDdimCD27low “naive” B cells and B cells with the IgDlowCD27hi (“plasmablasts”) phenotype was found in patients with mild brain contusion, compared to comparison group. Moreover, the number of “naive” mature B cells with the CD27lowCD38dim phenotype was significantly decreased compared with the controls.

Russian Journal of Immunology. 2022;25(4):471-476
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Influence of ZP2 peptide, a synthetic analogue of the GM-GSF active center on the anticytokine activity of bacteria from Enterococcus genus and their ability to produce cytokine-like substances
Pashinina O.A., Kartashova O.L., Pashkova T.M., Gritsenko V.A.

Peptide ZP2, a synthetic analogue of the active center of granulocyte-macrophage colony stimulating factor (GM-CSF), exhibits a wide range of immunobiological effects, including antibacterial activity. At the same time, its effect (in sub-inhibitory concentrations) on the biological properties of Enterococcus spp., the causative agents of many infectious and inflammatory diseases remains poorly understood. The aim of our study was to analyze the nature of the effect of synthetic peptide ZP2 on anti–cytokine activity (ACA) and its ability to produce cytokine-like substances (CLS) in Enterococcus spp.

18 clinical isolates of Enterococcus spp. were used. Over the experiments, the bacterial strains were cultured in Schaedler’s broth with ZP2 peptide at 37 °C for 24 hours. No specific peptide was added in the control. ACA for IL-8, TNFα and IL-17A and the production of the corresponding CLS were determined by the ELISA method. To assess ACA, the proportion of cytokine inactivation in the experiment relative to the control was calculated and expressed in pg/ml; CLS production was evaluated by the level of cytokines in the experiment and control, expressed as pg/ml. The data were subjected to statistical processing.

It was revealed that Enterococcus spp. strains are capable of secreting compounds that inactivate cytokines IL-8, IL-17A and TNFα, and produce CLS in the culture medium. Intragenital and intraspecific variability was noted in the presence and frequency of occurrence and in the severity of these properties. It was found that the ZP2 peptide in E. faecium increases ACA with respect to all studied cytokines. When tested with E. faecalis, it either did not affect their ACA against TNFα and IL-8, or completely inhibited ACA for IL-17A. At the same time, ZP2 blocked the production of CLS, e.g., IL-17A and IL-8 in E. faecium, but increased the production of CLS similar to TNFα, and, with E. faecalis, it increased the number of IL-17A-producing isolates twofold, although the average level of production of these CLS was lower than in the control.

Enterococcus spp strains are capable of secreting compounds that inactivate cytokines IL-8, TNFα and IL- 17A, and may produce substances similar to these cytokines. The synthetic peptide ZP2 has a modifying effect on the manifestation of these properties by Enterococci. Further studies of biological and pathogenetic features of Enterococci and other bacterial species, as well as modifying effects of the ZP2 peptide are required.

Russian Journal of Immunology. 2022;25(4):477-484
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Studying expression of IL-1β gene under the action of siRNA complexes with anti-influenza effect
Pashkov E.A., Pak A.V., Abramova N.D., Yakovleva I.V., Vartanova N.O., Bogdanova E.A., Pashkov E.P., Svitich O.A., Zverev V.V.

Influenza is one of the most urgent global health problems today. The influenza virus has immunosuppressive properties, which can lead to the development of secondary immunodeficiencies, interfering with the functioning of the interferon system activation, thus leading to impaired production of pro-inflammatory cytokines. IL-1β is the most important player in development of antiviral immunity. This cytokine plays an important role in boosting the expression of the MCP-1 and MCP-3 genes and maturation of macrophages and dendritic cells. Induction of IL-1β production occurs due to interaction of the ligand with Toll-like receptors. Currently, there is a lot of drugs aimed at the prevention and treatment of influenza infection. However, their use in some cases is difficult due to high mutational variability of the influenza virus, thus making it resistant to these drugs. Therefore, the issue of developing and creating effective methods to combat such infections is of particular importance. A promising approach to the treatment and prevention of viral respiratory infections may be connected with RNA interference. This process consists of degradation of foreign mRNA by small interfering RNA (siRNA) molecules. The aim of the present study was to evaluate expression of the IL-1β gene upon transfection of miRNA complexes directed to the cellular FLT4, Nup98, Nup205 genes. Evaluation of changed viral reproduction was carried out using titration by CPE virus-containing fluid. Expression level of the IL-1β gene was determined by means of real-time RT-PCR. Assessment of the changes in viral reproduction allowed us to reveal that the use of all the miRNA complexes directed to the cellular genes lead to a significant decrease in viral reproduction on the 1st day after infection. Usage of Nup205 + FLT4 and FLT4 + Nup205 + Nup98 complexes proved to cause a decrease in viral reproduction on the second day as well (p < 0.05), as compared with nonspecific and viral controls. When analyzing expression profile of the IL-1β gene, an increase in its expression was observed on the 1st day for all miRNA complexes and on the 2nd and 3rd days for the Nup98 + FLT4 and Nup205 + Nup98 complexes. In the course of the study, it was found that suppression of the cellular genes FLT4, Nup98 and Nup205 activities, which are necessary for viral reproduction, led to a significant decrease in viral activity and an increase in IL-1β expression.

Russian Journal of Immunology. 2022;25(4):485-490
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Evaluation of anti-TNF treatment efficiency in children with immune-dependent diseases by means of testing the NF-κB activity in lymphocyte populations
Petrichuk S.V., Radygina T.V., Kuptsova D.G., Kurbatova O.V., Semikina E.L., Murashkin N.N., Potapov A.S., Fisenko A.P.

Nuclear transcription factor κB (NF-κB) regulates innate and adaptive immunity functions and mediates inflammatory responses by activating proinflammatory cytokine gene transcription. TNF inhibitors block the NF-κB signaling pathway, thus reducing inflammatory activity. The aim of the study was to evaluate the informativity of NF-kB transcription factor determination in the lymphocyte populations in children with inflammatory bowel disease (IBD) and psoriasis to assess the efficacy of anti-TNF therapy. We have examined 124 children with IBD and 55 children with psoriasis vulgaris administered maintenance anti-TNF therapy, and 30 healthy children. Stratification into the study groups was carried out according to PCDIA, PUCAI, PASI indices (≤ 10, remission). The number of cells with NF-κB translocation was determined by flow cytometry with vusualization (Amnis ImageStreamX Mk II). Statistical evaluation was performed using Statistica 10.0 and SPSS 16.0. The highest number of cells with NF-κB translocation was detected in B-lymphocytes and NK cells, thus being significantly higher than in T helper cells and cytotoxic T lymphocytes (p = 0.000). The percentage of cells with translocation of NF-κB in populations of NK cells, T helper, cytotoxic T lymphocytes, Th17 lymphocytes, cytotoxic Th17 lymphocytes (Tc17) and Treg was increased in the patients at the acute disease stage against the comparison group. In the remission state, NF-κB activity in lymphocyte populations was lower than in acute stage. In remission of psoriasis, NF-κB activity in B lymphocytes, NK cells, and cytotoxic T lymphocytes was significantly lower than in comparison group. In IBD remission state, the NF-κB activity was elevated only in T-helper cells. The level of NF-κB translocation in the NK-cell population differed in children with IBD and psoriasis, both in acute phase (IBD, 46.2% (34-58); psoriasis, 36.5% (29-48), p = 0.041), and remission of disease (IBD, 25.4% (22-35); psoriasis, 19.1% (17-22), p = 0.000). ROC analysis of the data from “exacerbation/remission” states assessed as the NK cell numbers with NF-κB translocation showed a good quality of the stratification model (AUC > 0.8): The cut-off value in IBD was 41% (Se = 65.4; Sp = 89.1), and in psoriasis it was 23% (Se = 85.2; Sp = 94.7). The informativity of NF-κB translocation level in lymphocyte populations in children with IBD and psoriasis was shown to correlate with efficacy of anti-TNF therapy. Exacerbation the disease with decreased therapeutic response is characterized by NF-κB activation in lymphocyte populations in the children with IBD and psoriasis.

Russian Journal of Immunology. 2022;25(4):491-498
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Clinical genetic counselling and rehabilitation treatment of a patient with Guillain–Barré syndrome after COVID-19
Ponomareva N.Y., Koshelev R.V., Lazarev V.V., Kochetkov A.V.

The authors present a clinical case of rehabilitation after the development of Guillain–Barré syndrome, an acute autoimmune inflammatory polyradiculoneuropathy, in a patient who underwent a SARS CoV-2 infection. The patient previously manifested with severe comorbidities (arterial hypertension, hypercholesterolemia, type 2 diabetes mellitus, stenosing atherosclerosis of brachiocephalic arteries). A diagnostic panel of single nucleotide gene polymorphisms associated with risk factors of cardiovascular diseases, metabolic disorders, immunopathology, pharmacogenetics was applied using PCR-RT “Genetic Passport” test system, and the results were interpreted in order to predict potential complications, adverse drug reactions and the choice of biomarkers for preventive measures. We have compared clinical manifestations, comorbid background and the identified genotype features, as follows: minor homo- and heterozygous variants of ACE, AGT, CYP1A2, NOS3, PPARD, EDN, PALLD, SNX19 genes associated with predisposition to cardiovascular diseases, increasing the risk of dysregulation of blood pressure, development of endothelial dysfunction. The following gene variants were revealed: FXII, ITGA2, ITGB3, MTHFR, MTRR, MTR, PAI-1 that increase the risk of venous and arterial thrombosis, along with gene variants of ADRB3, FTO, INSIG2, KCNG11, LEP, PPARD, TCF7L2, ApoC3, PON1 associated with carbohydrate and lipid metabolism disorders; polymorphisms in the genes determining the immune response, i.e., IL4, IL6, IL8, IL10, CDH1, BDNF1, CRP, CCR5 (with del32 allele considered a risk factor of severe SARS-CoV-2), homozygous polymorphism of a gene of FCGR2 associated with risk of antigen-antibody-complement-mediated cytotoxicity, circulation arrest, deposition of immune complexes in endothelium of microvessels, decreased antithrombotic effects and increased procoagulant activity. Pharmacogenetic study revealed a variant of the CYP4F2 gene, a CYP2C19 gene polymorphism associated with delayed metabolism of a number of pharmaceuticals which requires higher drug dosage, or choosing a drug with a different mechanism of action; gene variants of CYP1A2, GSTP1, GSTT1 reducing efficiency of the cellular detoxification system; NAT2*5 and NAT2*6 variants determining a decrease in appropriate enzyme activities when administering a standard dose of drugs with slowdown of their detoxification, accumulation of toxic metabolites causing clinical adverse effects (hepatotoxicity, dyspepsia, lupus-like syndrome, polyneuritis). Based on the genotype that determines pathogenesis of the multifactorial pathology (including immune-mediated complications of COVID-19), a personalized approach is recommended to the patient, in terms of treatment and prevention of complications. On the basis of testing the biochemical, immunological and blood coagulation biomarkers, an adequate choice of pharmaceuticals is recommended for the patient.

Russian Journal of Immunology. 2022;25(4):499-504
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Cytokines of the IL-6 family, adiponectin and leptin levels in patients with metabolic syndrome during the post-COVID period
Radaeva O.A., Simbirtsev A.S., Kostina Y.A., Negodnova E.V., Besheynov D.D., Mashnina S.V., Eremeev V.V.

COVID-19 is a multisystem disease, but the extent of its consequences is currently poorly understood, especially in the persons with metabolic disorders. The aim of the present study was to evaluate the special changes in the cytokines of IL-6 family (IL-6 and sIL-6, LIF and sLIFr), adiponectin and leptin within 360 days after SARS-CoV-2 infection in the patients with metabolic syndrome (MetS), to discern features of immunopathogenesis depending on previous vaccination against COVID-19.

We have classified the patients in two groups: (1) patients with MetS who underwent COVID-19 6-12 months after full-course vaccination with a vector vaccine (n = 32); (2) patients with MetS who underwent COVID-19 without story of vaccination (n = 29). Control group included conditionally healthy individuals without MetS: (3) vaccinated, and (4) non-vaccinated, who also had COVID-19. The levels of IL-6 and sIL-6, LIF and sLIFr, leptin and adiponectin, NO, ADMA, SDMA were determined by ELISA technique.

In patients with MetS, changes in cytokine regulation towards proinflammatory reactions were revealed (an increase in blood IL-6 and leptin levels), which was most pronounced in MetS within first 30 days post-COVID, but with a number of changes which remained for 12 months (e.g., increased leptin concentration in blood). Vaccination against COVID-19 reduced the severity of pro-inflammatory changes in the sIL- 6r/ IL-6 and leptin/adiponectin systems towards protective adiponectin. However, the persistent increase in leptin was not canceled. When interpreting these results, no negative differences were revealed in the group of once vaccinated individuals with MetS, concerning the mentioned cytokine regulations of MetS over 1 year after COVID-19. The univariate, and then multifactorial correlation analysis between serum contents of sIL- 6r/ IL- 6, LIF/ sLIFr, adiponectin and leptin and the levels of vasoactive substances (NO, ADMA and SDMA), glycated hemoglobin, LDL has shown that the increased ratio of sIL-6r/IL-6 is an independent factor for the NO reduction of (r = 0.74, p < 0.01); an increase in sLIFr positively correlates with increase in glycated hemoglobin (r = 0.69, p < 0.01), and an association with increase of ADMA (r = 0.82, p < 0.001), leptin (in this model) are shown to be an independent factor of LDL increase (r = 0.69, p < 0.05).

Influence of «pre-COVID» modifiable factors, in particular, vaccination, is relevant in terms of reducing the likelihood of progression of pre-existing chronic diseases (hypertension, atherosclerosis, diabetes mellitus) in the persons with MetS after COVID-19 and has prospects for implementation into clinical practice.

Russian Journal of Immunology. 2022;25(4):505-514
pages 505-514 views
Role of cytokines, neuropeptids and matrix metalloproteinases in the immunopathogenesis of retinal neurodegeneration in diabetic retinopathy
Ruchkin M.P., Markelova E.V., Fedyashev G.A., Yuschyuk V.N.

Currently, diabetic retinopathy (DR) is considered both a vascular lesion, as well as a neurodegenerative disease. The normal functioning of the glia and retinal neurons depends on the balance between the cytokine system, neurotrophic factors and matrix metalloproteinases. The disorders that occur in these systems are assigned an important role in many neurodegenerative processes. The purpose of the present study was to determine the levels of IL-1β, IL-17A, TNFα, IFNγ, IL-10, TGF-β1, TGF-β2, TGF-β3, MMP- 2, MMP-7, MMP-9, TIMP-1, TIMP-2, S100b protein, BDNF and NGF in the serum of patients with type 2 diabetes mellitus with signs of retinal neurodegeneration, and to identify additional immunological markers for diagnosis and prediction of their clinical course. The study included 80 patients with endocrinogically verified diagnosis of type 2 diabetes. All subjects were examined at an optical coherent tomograph RTVue-100 (USA), and the volume of focal loss of retinal ganglion cells (FLV) was determined. According to its results, the patients of the main group were divided into 2 subgroups. The first group included 22 persons in whom the FLV indexes did not show significant differences from the controls. The second group included 58 patients with a significantly larger FLV volume. In the subgroup of patients with high level of focal GCS loss, a significant increase in the level of IL-1β and IL-10 deficiency was revealed in comparison with the controls, and the subgroup without significant losses of GCS over the entire observation period. TGF-β3 deficiency was found in patients of subgroup 2 versus controls and subgroup 1. An imbalance in the tissue proteolysis system was revealed, MMP-9 and TIMP-2 levels were elevated, and MMP-7 levels were decreased in both subgroups compared to controls. When analyzing serum contents of neurospecific proteins in the group of patients with OCT signs of retinal neurodegeneration, high levels of the S100b protein and NGF were revealed, in contrast to the control group and subgroup 1.

Russian Journal of Immunology. 2022;25(4):515-520
pages 515-520 views
Changes in mononuclear cell subsets in capillary and venous blood of patients with psoriasis depending on the treatment
Sennikova S.V., Toptygina A.P.

Topical glucocorticoids are conventionally used to treat psoriasis, but such treatment provides a short-term effect, and may cause various complications during long-term usage. A detailed study of the immunopathogenesis of psoriasis has made it possible to use bioengineered drugs that block the main cytokines. It has been shown that IL-36 plays an important regulatory role in pathogenesis of psoriasis. The aim of the study was to study therapeutic effect of patients with psoriasis using topical glucocorticoid hormone versus IL- 36 receptor antagonist (RAIL-36), with respect to clinical course of psoriasis and the subsets of mononuclear cells in venous and capillary blood taken close to the focus of inflammation. 16 patients with psoriasis (group 1a) received 0.1% mometasone cream for 14 days; 20 patients of group 1b received a gel containing 0.4% recombinant RAIL-36 for 14 days. Control group included 20 healthy adults. Treatment efficacy was assessed by PASI, DISHS and DLQI indices. 19 lymphocyte subsets and 3 monocyte subsets were assessed by four-color staining of whole capillary and venous blood with erythrocyte lysis using BD Biosciences (USA) technologies and reagents. It was shown that both drugs led to a decrease in the severity of the disease at the end of treatment. However, 2 weeks after the end of treatment in group 1a, the disease indexes nearly returned to the initial values. Meanwhile, the reduced index levels persisted 2 weeks later in group 1b. Significant deviations (more pronounced in capillary blood) were revealed for the levels of several leukocyte subsets in the psoriasis patients compared with healthy persons. As a result of treatment, we have revealed some changes in the levels of leukocyte subsets common to the two groups, and special differences for the two treatment options, that were more pronounced in capillary blood samples. Both medical preparations used are suitable for treatment of psoriasis.

Russian Journal of Immunology. 2022;25(4):521-528
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Dynamics of immune system parameters in development of SARS-CoV-2-specific immunity in a patient with common variable immune deficiency
Sizyakina L.P., Andreeva I.I., Kharitonova M.V.

With the accumulation of data on the evolving SARS-CoV-2 infection pandemic, it became clear that the risk factors for severe course of COVID-19 among the patients with primary immunodeficiency include disorders associated with dysregulation of the immune response. In this regard, it is of interest to identify possible predictors of the pronounced inflammatory reaction upon infection with coronavirus in the patients with general variable immune insufficiency. For this purpose, the dynamics of immune system parameters was studied in a patient with CVID who underwent a severe clinical variant of COVID-19, as an example of clinical case.

We present patient K., 49 years old, with CVID diagnosis verified at the age of 35 years who received regular replacement therapy with IVIG. He suffered from COVID-19 in severe form, received anti-cytokine therapy and an additional course of IVIG during the treatment. He was discharged in satisfactory condition. The quantitative and functional parameters of the T and B lineages of immune system were evaluated by flow cytofluorimetry during routine examinations before the infection and three months after the discharge from the hospital after COVID-19. It has been shown that, before the disease, there were changes in the parameters of B cells characteristic of CVID manifesting as a decrease in switched-memory B cells and plasmoblasts. Alterations in the T cell subsets were also revealed, as redistribution of the subpopulation composition towards T effectors with an increased cytolytic potential of these cells and a weakening of T cell suppression, due to decreased Treg in peripheral blood. After undergoing COVID-19, the patient developed specific IgM and IgG antibodies. The development of immune response was accompanied by an increase in the number of un-switched and switched memory B cells. At the same time, we have registered an increase in memory T cells ready for the proliferative response of T helper cells and Treg cells. The initial pro-inflammatory pattern of the T cell lineage system in our patient with CVID is explained by the implementation of the compensatory capabilities of the immune system, thus leading to activation of the cytolytic effects of cellular compartment in adaptive immune response, along with attenuation of the humoral component. Moreover, it is likely that these changes contributed to the clinical course of COVID-19 in this clinical case. Development of a specific humoral response to SARS-CoV-2 in a patient with CVID after a COVID-19 infection is accompanied by an increased proportion of memory B cells, coordinated dynamics of T cell suppression and activation parameters.

Russian Journal of Immunology. 2022;25(4):529-534
pages 529-534 views
Association of the cytokine profile and metabolic syndrome components in young patients
Sumerkina V.A., Telesheva L.F., Golovneva E.S.

The components of metabolic syndrome (MS) are independent factors of cardiometabolic risk and are associated with impaired humoral immunity. However, the literature data on the cytokine profile features in MS are ambiguous. Therefore, associations between cytokine levels and MS components were determined in a group of MS patients of both sexes, as well as indices of visceral adipose tissue function were studied. The work included 149 patients aged 18-45 years. The patients were divided into 2 groups: group 1 (n = 71) included patients without abdominal obesity and MS components (comparison group); group 2 (n = 78), patients with MS. The concentrations of glucose, glycosylated hemoglobin, insulin, total cholesterol, HDL-C, LDL-C, triglycerides, leptin, adiponectin were determined. The indexes of insulin resistance HOMA-IR, Tg/HDL and TyG, as well as marker of visceral adipose tissue dysfunction VAI were calculated. ELISA technique was used to determine the concentration of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IFNα, IFNγ, МСР-1 и TNFα. Results: In the patients with MS, we have found increased levels of IL-6, IL-10, MCP-1, and decrease of IL-2, IL-4, IFNγ levels. Correlation analysis established a relationship between glucose levels and MCP-1; glycosylated hemoglobin and IL-6, TNFα. Among the indices of lipid metabolism, we have revealed some associations between LDL-C and IFNγ; HDL-C and IL-2, IL-4, IFNγ. The levels of triglycerides correlated with MCP-1. A negative relationship between the presence of arterial hypertension and the IL-4 contents was established. A negative correlation of leptin levels with IL-4 and IFNγ concentrations was also determined. Markers of insulin resistance (Tg/HDL and TyG) were associated with MCP-1 chemokine, thus supporting chronic inflammatory process. The VAI index, which reflects the dysfunction of visceral adipose tissue, showed a correlation with MCP-1. Thus, the results of investigation suggest an involvement of the cytokine system in the disorders of visceral adipose tissue and development of the metabolic syndrome.

Russian Journal of Immunology. 2022;25(4):535-540
pages 535-540 views
Innate immune response in the patients with heart disease and acute kidney injury after coronary artery bypass grafting, depending on the duration of extracorporeal circulation
Fomina O.I., Chagina E.A., Fedyanina L.N., Krasnikov V.E.

Incidence of chronic diseases is increased in the 21st century due to prolonged life expectancy. Cardiovascular disease is the most common disorder worldwide, complicated with high morbidity and mortality. Upon increased prevalence of this disease, cardiac surgery has become an essential strategy for patients that do not respond to medications and other therapeutic procedures. Some potential complications in cardiac surgery affect kidneys, lung, brain over the postoperative period. Acute kidney injury (AKI) is considered a serious complication of cardiac surgery characterized by rapid loss of kidney function leading to acute increase in the serum creatinine concentration. AKI occurs in up to 30% of patients after cardiac surgery and is observed in 2% of the cases with isolated coronary artery bypass grafting (CABG). There are literature data concerning the patients with coronary artery disease after CABG in the presence of evolving atherosclerosis. Development of inflammation and dysadaptation of innate immunity was established in this work. An imbalance in the cytokine system contributes to the progression of endothelial dysfunction and may promote development of renal injury after CABG. Hypercytokinemia in AKI patients suggests involvement of innate immunity factors in the development of acute inflammatory response. The purpose of this article was to assess the innate immune response in the patients subjected to CABG with different duration of extracorporeal circulation. In the present study, 100 patients underwent CABG, all of whom were in the on-pump group. General clinical, functional, biochemical, instrumental, immunological and statistical methods were used in the work. After analyzing the data on the content of pro- and anti-inflammatory cytokines in blood serum of the patients with stage 1 and 2 AKI (KDIGO), depending on the duration of cardiopulmonary bypass surgery, we found that their dynamics corresponded to the standard pattern of changes after CABG groups and hyperproduction of pro- and anti-inflammatory cytokines in the groups with higher duration of cardiopulmonary bypass. The pathogenetic role of pro- and anti-inflammatory mediators remains unclear. We support the view that the clinical prognosis after cardiopulmonary bypass depends on the balance of pro- and anti-inflammatory cytokines.

Russian Journal of Immunology. 2022;25(4):541-548
pages 541-548 views
Mucosal immunity during rehabilitation in the patients after coronavirus infection
Khasanova A.А., Kostinov M.P., Soloveva I.L.

Following the coronavirus infection, a variety of symptoms may persist for a long time. Therefore, an important area of further research is to study the state and response of protective immune mechanisms in the post-COVID period. Our aim was to evaluate the dynamics of mucosal immunity by measuring sIgA in the saliva samples and nasal swabs (sIgA, lactoferrin), as well as efficiency of interferon-alpha-2b (IFNa2b) treatment in the patients after coronavirus infection.

A study was conducted in the patients aged 18 to 60 years (n = 130) at the terms of 1 to 9 months after a coronavirus infection. A control group consisted of conditionally healthy individuals (n = 15). Diagnosis of post-COVID manifestations was carried out by collecting complaints, anamnestic data, physical examination and questionnaire. The state of mucosal immunity in saliva samples and nasopharyngeal mucosal scrapings was evaluated in dynamics as based on determination of sIgA and lactoferrin concentrations by means of enzyme immunoassay techniques prior to administration of local preventive therapy with recombinant IFNa2b, and 1 month after the treatment (“VIFERON”® gel applied intranasally twice a day for 30 days).

The following symptoms of post-COVID syndrome were documented In the study group: joint and muscular pain, shortness of breath, cough, fatigue and weakness, headache and dizziness, anxiety. In the group of patients who received preventive therapy during 1 to 3 months after coronavirus infection, a significantly increased level of saliva sIgA was noted, respectively, 1.84±0.28 to 5.78±1.96 mg/mL. As based on the data obtained with scrapings from nasopharyngeal mucosa, a significant increase in the level of sIgA was revealed in the group subjected to therapy up to 3 months after COVID-19 infection, i.e., from 28.61±3.0 to 39.83±3.85 mg/mL. In the group of patients devoid of preventive therapy, a stable maintenance of the reduced mucosal immunity parameters was found in all time intervals during the period of convalescence. In all observed patients, regardless of the group, a decreased lactoferrin level was found, being two-fold lower than the normal reference values. The incidence of respiratory viral infections in the group without preventive therapy was statistically significant, being registered in 9.2% of cases.

Patients after COVID-19 infection exhibit a persistent decrease in mucosal immunity. Immunological efficacy was observed when using IFNa2b, thus making it possible to recommend it for rehabilitation in this group of patients over the period of convalescence.

Russian Journal of Immunology. 2022;25(4):549-554
pages 549-554 views
Role of innate errors of immunity in the group of children with fatal outcomes during the first year of life
Cheremokhin D.A., Tuzankina I.A., Chereshnev V.A., Bolkov M.A., Shinvari K.

In the modern world, inborn errors of immunity (IEIs), or primary immunodeficiencies (PIDs), are among of the main causes of childhood disability and mortality, determining the demographic state of mankind not only at present, but also in the future. In the Sverdlovsk Region over the past 5 years, there were about 30% of children who died from severe combined primary immunodeficiency. This retrospective study is devoted to the study of the nosological profile of mortality in the children with immune-dependent disorders in the Sverdlovsk Region, as well as to assess information significance of extrachromosomal circular DNA molecules (TREC and KREC) analysis. Some anamnestic data on the course of prenatal period in the current and previous pregnancies were considered the signs of suggested diagnosis of primary immunodeficiencies, i.e., threats of pregnancy loss at the early terms, documented cases of early childhood death, persistent viral and bacterial infections in the mother, complicated course of pregnancy in the mother, as well as some clinical manifestations, including fungal-bacterial sepsis, generalized viral infection, repair disorders, reduced physiological tolerance accompanied by autoimmune organ damage and uncontrolled systemic inflammation. The study demonstrated a wide range of nosological entities of innate errors of immunity in the structure of early childhood mortality, including both classical forms of primary immunodeficiencies and the disorders not directly related to innate errors of immunity, but those showing phenotypically pronounced immunodeficiency and their immediate role in statistical deviations. Among the main criteria that may presume possible presence of an immune-dependent pathology in the early neonatal period we considered the molecular markers of naive T and B cells (TREC and KREC, respectively) revealed in 70% of the cases studied, with, at least, one of these indexes found to be reduced. It is important to understand that primary immunodeficiencies are not as rare as previously thought. Therefore, it is necessary to carry out timely and high-quality diagnostics, in order to avoid unavoidable deaths.

Russian Journal of Immunology. 2022;25(4):555-560
pages 555-560 views
Changes of blood serum cytokine profile in the patients with papillomavirus infection before and after therapeutic pregravid preparation
Chernikova M.A., Markelova E.V., Nevezhkina T.A., Matyshkina L.S., Tulupova M.S., Knysh S.V., Shevchenko K.G.

Human papillomavirus is one of the most common sexually transmitted viruses. The state of the immune system is fundamental to the outcome of infectious processes of viral and bacterial genesis, thus determining the quality of pre-gravidar preparation. The purpose of present study was to perform a comprehensive analysis of pro- and anti-inflammatory cytokines in papillomavirus infection and to provide immunological assessment of therapeutic efficiency in women. Materials and methods: 137 patients with papillomavirus infection were observed, at the average age of 31±2.5 years old. The study consisted of 2 stages: stage 1 included analysis of humoral innate immunity in women of the main group, distributed according to etiological factor, i.e., G-I was with papillomavirus infection (PVI); G-II presented with papillomavirus and herpetic infection (PVI + HVI 1/2 type); G-III included the patients with papillomavirus and Chlamydia infection (PVI + Trash.). At Stage 2, we performed immunological analysis of the therapeutic efficiency for PVI: in G-IA group with papillomavirus infection (PVI) we used Inosine pranobex (n = 11); in the IB group, Solanum tuberosum was applied (n = 10); in G-II A group with papillomavirus and herpes infection (PVI+HVI 1/2 type), we used Valacyclovir + Inosine pranobex (n = 24); in G-IIB patients Valacyclovir + Solanum tuberosum were administered (n = 23); for G-IIIA group with papillomavirus and chlamydia infection (PVI + Trash.) Doxycycline + Inosine pranobex were used (n = 20); the patients from IIIB group were treated with Doxycycline + Solanum tuberosum (n = 19). Determination of levels of IL-17A, IL-12 p70, IL-12 p40, IL- 13 in blood serum was carried out using specific reagents from R&D Diagnostics Inc. (USA). Results: Before therapy, an increase in IL-17 and IL-13 (p < 0.05), and a pronounced deficiency of IL-12 p40 and IL-12 p70 (p < 0.001) were observed in blood serum of the patients. After the course of therapy, a decrease in IL-13 and an increase in IL-12 p40 and IL-12 p 70 were found. The IL-17 level remained without dynamic changes. The applied therapeutic approaches had a positive effect in all studied groups of patients, regardless of the drug administered.

Russian Journal of Immunology. 2022;25(4):561-570
pages 561-570 views
Modulating effects of hexapeptide on the altered phenotype of neutrophil granulocyte CD16+CD62L+CD11b+CD63- and CD16+CD62L+CD11b+CD63+ subsets in children with acute osteomyelitis in the in vitro system
Chudilova G.A., Teterin Y.V., Chapurina V.N., Chicherev E.A., Tarakanov V.A., Nesterova I.V.

The problem of acute osteomyelitis in children is of special importance among the inflammatory diseases of musculoskeletal system, due to infectious conditions arising in the body and spreading to the bone tissue caused by impaired immune regulation, first of all, concerning neutrophilic granulocytes. Of interest is studying the subsets of neutrophilic granulocytes arising when the cells are involved into the inflammatory process in acute pediatric osteomyelitis, and determining the opportinity to influence the level of receptor expression aiming for correction of their functions. The purpose of our study was to evaluate the effect of hexapeptide arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine on the altered phenotype of neutrophilic granulocytes in children with acute osteomyelitis using an in vitro experimental model. We examined the peripheral blood samples from children with acute hematogenous or post-traumatic osteomyelitis at the age of 10 to 17 years (n = 12) upon their admission to the hospital, and from healthy children (n = 7). Blood samples from children with acute osteomyelitis were incubated with hexapeptide (10-6 g/L) for 60 min, at 37 °C. The content of neutrophilic granulocyte subsets (CD16+CD62L+CD11b+CD63- and CD16+CD62L+CD11b+CD63+), expression density of appropriate membrane receptors were assessed by flow cytometric technique (FC 500 “Beckman Coulter”, USA). Phagocytic function was studied by assessing the degree of completed phagocytosis of S. aureus. It was found that, in acute osteomyelitis, a 8.5-fold increased proportion of activated CD16+CD62L+CD11b+CD63+NG subset with the CD16brightCD62LbrightCD11bbrightCD63dimNG phenotype was revealed, along with a decrease in the CD16+CD62L+CD11b+CD63-NG subset and changes in the CD16dimCD62LbrightCD11bmidCD63- NG phenotype as compared with reference indexes of healthy children. At the same time, an increased number of actively phagocytic cells was noted, however, with decreased indexes characterizing capture and digestion of the bacterial antigen. In the in vitro experiments, the tested hexapeptide was shown to modulate the phenotypes of both studied subsets (CD16brightCD62LmidCD11bmidCD63- and CD16midCD62LmidCD11bmidCD63dimNG), thus promoting restoration of the receptor expression levels to the reference group values, as well as phagocytic activity, in terms of uptake and digestive capacity of microbial cells. Thus, the dominance of a diagnostically significant activated CD16+CD62L+CD11b+CD63+ neutrophil subset with the CD16brightCD62LbrightCD11bbrightCD63dimNG phenotype was found in acute osteomyelitis in children. The results of in vitro studies have shown that the hexapeptide caused phenotypic modulation of the CD16+CD62L+CD11b+CD63- neutrophils, and CD16+CD62L+CD11b+CD63+NG subsets, along with recovery of their phagocytic activity. In the future, our results may provide a basis for the development of new effective therapeutic regimens.

Russian Journal of Immunology. 2022;25(4):571-576
pages 571-576 views

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