Vol 23, No 4 (2020)

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Examining effects of NS1 specific antibodies on sublethal influenza infection and secondary bacterial pneumonia in mice

Kartashova N.P., Leneva I.A., Falynskova I.N., Poddubikov A.V.


Influenza is a highly contagious respiratory disease widespread throughout the world that causes disease in humans, birds and many mammalian species. Annually, around 20% of the global human gets sick with influenza so that more than 500,000 people die its various complications. Secondary bacterial pneumonia poses the peak threat during influenza infection, being most frequently caused by S. pneumoniae. Multiple studies in humans confirm the negative impact of influenza virus infection on subsequent outcome of bacterial pneumonia and provides insight into increased morbidity and mortality due to complicated influenza infection. In particular, the last 2009 influenza pandemic caused by H1N1 virus revealed that 25-56% cases of severe disease forms were associated with secondary pneumonia, among which 14-46% of them were fatal. Based on the aforementioned, it is of high priority to investigate a role of influenza virus proteins in developing of pathogen synergism in viral-bacterial pneumonia, particularly influenza virus non-structural protein NS1. The study objective was to examine effects of NS1-specific antibodies on course of influenza infection and secondary bacterial pneumonia in mice. For this, we used an experimental model of sublethal influenza infection followed by secondary Streptococcus pneumoniae bacterial pneumonia. Influenza A/Puerto Rico/8/34 (H1N1) virus and S. pneumoniae No. 3405 strain were used to simulate influenza infection. Rabbit serum containing antibodies against recombinant NS1 protein from A/Puerto Rico/8/34 virus and native rabbit serum (contain no specific antibodies) were used for vaccination. The study was carried out with female BALB/c mice, weighing 20-22 g. Protective activity of animal serum was assessed by using the three criteria: infection-related mortality, life expectancy and body weight change. The data obtained showed that passive transfer of antibodies specific to influenza virus NS1 protein did not lowered viral replication in sublethal murine model of influenza infection. Subsequent secondary bacterial pneumonia induced by S. pneumoniae revealed no protective effect of anti-NS1 protein antibodies assessed by measuring survival rate, lung viral and bacterial titers in treated vs. control mice.

Russian Journal of Immunology. 2020;23(4):383-388
pages 383-388 views

Examining protective efficacy of influenza virus NA-containing virus-like particles (VLP) in mouse model of post-influenza bacterial pneumonia caused by Staphylococcus aureus

Glubokova E.A., Leneva I.A., Falinskova I.N., Poddubikov A.V.


Currently, pneumonia resulting from post-influenza infection still remains a pressing issue. In particular, virtually no studies regarding a role of immune response against influenza virus neuraminidase in regulating host susceptibility to subsequent bacterial superinfection are now available. Virus-like particles represent one of the new and promising approaches in contemporary virology for developing influenza vaccines and studying influenza virus proteins. Upon that, it is possible to obtain virus-like particles carrying individual influenza virus-derived proteins such as neuraminidase and hemagglutinin. This allows to get closer insight into potential role of individual influenza virus proteins for host immune response as well as assess a risk of developing secondary bacterial pneumonia. In this study we examined an immune response against influenza virus NA protein and its impact in generating resistance to secondary bacterial pneumonia by using neuraminidase-bearing virus-like particles. We used an experimental model of secondary bacterial pneumonia induced by Staphylococcus aureus after influenza infection. Animals were preliminarily vaccinated with virus-like particles carrying neuraminidase, hemagglutinin, or both (a cocktail of virus-like particles). In this model vaccinated animals were infected 21 days later with influenza viruses A/Puerto Rico/8/34 (H1N1) and reassortant strain NIBRG-121xp (A/California/04/2009 (pndm H1N1 2009) X A/Puerto Rico/8/34 ( H1N1) bearing surface proteins hemagglutinin and neuraminidase derived from the A/California/04/2009 virus as well as the internal proteins derived from A/Puerto Rico/8/34. Next, 5 days after influenza infection mice were infected with Staphylococcus aureus. Moreover, animals in one group were simultaneously vaccinated and infected with A/Puerto Rico/8/34 (H1N1) followed by inoculation on day 21 with reassortant virus NIBRG- 121xp. The protective vaccine activity was assessed by measuring survival rate, life expectancy and decreased body weight loss. The data obtained showed that virus-like particles containing neuraminidase revealed no protective activity. However, a cocktail of virus-like particles, containing hemagglutinin and neuraminidase, protected animals from lethal outcome as well as body weight loss. Moreover, the increase virus-like particles containing neuraminidase in the cocktail of virus-like particles (virus-like particles containing neuraminidase + hemagglutinin) led to elevated protective effect after vaccination that was comparable or even superior to that one in mice with post-infectious immunity.

Russian Journal of Immunology. 2020;23(4):389-394
pages 389-394 views

Experimental in vitro reprogramming of CD64-CD32+CD16+CD11b+ and CD64+CD32+CD16+CD11b+ neutrophilic granulocytes by arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine in modelled virus-bacterial coinfection

Chudilova G.A., Nesterova I.V., Pavlenko V.N., Rusinova T.V., Kovaleva S.V.


Disruption of neutrophilic granulocyte (NG) functioning underlies one of the key causes for negative polymicrobial synergism during virus-microbial co-infections. In connection with this, it is important to develop experimental models for viral-bacterial co-infections in vitro, which might allow to uncover NG involvement in effector events and assess reorganization of inter-connected functionally relevant NG receptors in response to various immunotropic agents. Understanding molecular mechanisms related to any molecule including drug molecules provides its safe use allowing them to become drug of choice. NG functional activity is associated with surface receptors CD64, CD32, CD16, CD11b, which are assigned to several NG subsets exhibiting distinct phenotypes, and their activation leads to complex processes of pathogen elimination. Study objective: to elucidate types of phenotype transition for NG subsets CD64-CD32+CD16+CD11b+ and СD64+CD32+CD16+CD11b+ and assess an opportunity for phenotype reprogramming exposed to hexapeptide arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine (НP) in experimental in vitro model of viral-bacterial coinfection. Materials and methods. We examined 39 samples of peripheral blood (PВ) collected from healthy adult volunteers (7 women, 6 men) aged 21 to 32 years, subdivided into 3 groups: comparison group 1 (intact NG); comparison group 2 – model of viral-bacterial infection; Study group – to assess HP effects. Model of viral-bacterial co-infection was created by incubating PВ samples sequentially with dsRNA (10-7M) for 60 min followed by fMLP (10-7M) for 60 min, 37 °С. To assess HP effect, PC samples preincubated with dsRNA and fMLP were next exposed to HP (10-6 g/L) for 60 min at 37 °С. We analyzed percentage of CD64-CD32+CD16+CD11b+ and СD64+CD32+CD16+CD11b+NG subsets as well as receptor expression density (MFI) by flow cytometry (FC 500, Beckman Coulter, USA) using MAbs (Beckman Coulter International SA, France). Results. Transformation of CD64-CD32+CD16+CD11b+ and СD64+CD32+CD16+CD11b+NG subset phenotype was experimentally revealed in virus-bacterial model manifested as upregulated expression of all receptors examined. Our data on HP effects ambiguously demonstrated phenotype transformation in CD64-CD32+CD16+CD11b+NG, СD64+CD32+CD16+CD11b+NG in in vitro viral – bacterial coinfection model contributing to recovery of proper NG response.

Russian Journal of Immunology. 2020;23(4):395-402
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Sensitivity of archival and clinical enterobacteria strains to synthetic GM-CSF active center ZP2 peptide

Zurochka A.V., Dobrynina M.A., Zurochka A.V., Gritsenko V.A.


Objective: to study sensitivity of various enterobacterial species to the bactericidal action of the ZP2 synthetic GM-CSF active center peptide after long-term storage.
In vitro experiments were carried out with archival archival test strains Escherichia coli K12 (GISK 240367) and E. coli (ATCC 25922), as well as 104 clinical isolates of E. coli (n = 22) and Klebsiella pneumoniae (n = 82) obtained from patients with surgical pathology. The bactericidal effect of the ZP2 peptide (final concentration 10 μg/ml) on microorganisms was assessed by measuring optical density (OD) difference between experimental and control broth cultures after 20 min exposure of bacterial suspensions (5 × 108 CFU/ml) with the ZP2 peptide (in control – with distilled water), added with meat-peptone broth and incubated at 37 °C for 4 hours. The ZP2 peptide effect was presented as Bactericidal Activity Index (BAI, %).
It was experimentally found that the archival E. coli test strains as well as most of examined clinical strains of E. coli and K. pneumoniae (95.5 and 97.6%, respectively) showed sensitivity to the bactericidal effect of the synthetic ZP2 peptide (at a final concentration of 10 μg/ml ) with BAI averaging 77.6±3.5 and 82.8±1.6% and its relatively wide variation range 45.8 ... 98.9 and 42.1 ... 99.8%, respectively.
The 5-year storage of synthetic ZP2 peptide at 8 °C exerted bactericidal effect on antibiotic-resistant enterobacterial strains. The data obtained can be used to develop ZP2 peptide-based drugs aimed at combating pyo-inflammatory processes caused by antibiotic-resistant E. coli and K. pneumoniae strains.

Russian Journal of Immunology. 2020;23(4):403-410
pages 403-410 views

Effects of NOD1 and NOD2 agonists polymuramyl as well as NOD2 agonist glucosaminylmuramyldipeptide on phenotype of neutrophile granulocyte CD64-CD16+CD32+CD11b+, CD16+CD62L+CD63-, CD16+CD62L+CD63+ subsets

Nesterova I.V., Chudilova G.A., Pavlenko V.N., Kovaleva S.V., Tarakanov V.A., Barova N.K.


Antimicrobial activity of neutrophilic granulocytes (NG) is based on effective recognition and elimination of microbial pathogens, as well as on complex intracellular signal transduction pathways interconnecting these processes. NG dysfunction leads to emergence of atypical infectious and inflammatory diseases recalcitrant to standard interventions, which requires new vector platforms aimed at restoring normal NG functioning and overcoming antibiotic resistance. Moreover, we emphasize about special interest paid to the NOD1 and NOD2 agonist polymuramyl and NOD2 agonist glucosaminylmuramyldipeptide. Objective of the study was to compare effects triggered by NOD1 and NOD2 agonist polymuramyl and NOD2 agonist glucosaminylmuramyldipeptide on phenotype of neutrophilic granulocyte subsets CD64- CD16+CD32+CD11b+, CD16+CD62L+CD63-, CD16+CD62L+CD63+ in the in vitro system. 64 samples of peripheral blood (PC) collected from 8 apparently healthy children (4 boys and 4 girls) aged 3 to 9 years were examined by flow cytometry (FC 500, Beckman Coulter, USA) assessing NG surface receptors CD64, CD16, CD32, CD11b, CD62L, CD63 with MonAb (Beckman Coulter International S. A., France) by analyzing NG number (%) expressing receptors examined, density of receptor expression measured as mean fluorescence intensity (MFI). For this, there were assessed intact peripheral blood NG from apparently healthy children (comparison group) as well as those exposed to polymuramyl (PM) (at concentration of 10-6 g/l) or glucosaminylmuramyl-dipeptide (GMDP) (at concentration of 10-6 g/l) for 60 minutes at 37 °С temperature. Comparative analysis of surface receptor expression was performed on CD64-CD16+CD32+CD11b+, CD16+CD62L+CD63- and CD16+CD62L+CD63+ NG subsets that suggested about positive transformation of activation parameters in circulating NG exposed to NOD1 and NOD2 agonist polymuramyl as well as NOD2 agonist glucosaminylmuramyldipeptide. At the same time, similar effects of varying intensity were revealed manifested as increased count of NG subsets CD16+CD62L+CD63+ bearing increased level of CD16 and reduced CD62L expression, as well as differences uncovered as significantly increased expression of surface membrane molecules CD16 and CD11b in CD64-CD16+CD32+CD11b+ NG subset from apparently healthy children exposed to polymuramyl as well as increased surface CD32 expression after incubation with GMDP.

Russian Journal of Immunology. 2020;23(4):411-418
pages 411-418 views

Features of peripheral blood B cell phenotype in patients with pressure ulcers

Borisov S.A., Savchenko A.A., Kasparov E.V., Fokin V.A., Matsenko M.V., Kudryavtsev I.V., Borisov A.G.


Pressure ulcers represent most common surgical pathology in the pattern of nosocomial complications. However, no unified mechanism leading to development of pressure ulcers has been proposed yet despite the lead role played by compression and immobilization. In this regard, examining immune system as the main component maintaining integrity of anatomical barriers in the skin and mucous membranes seems highly promising for creating new methods to prevent and treat pressure ulcers. Our study was aimed at investigating phenotypic profile of peripheral blood B cells in patients with pressure ulcers. There were enrolled 67 patients complicated with pressure ulcers at the Department of Surgery. Examination of pressure ulcers included determining anatomical localization, investigating depth (degree) and size of the lesion (by measuring wound area), skin color and assessing nature of pressure ulcer edges and edema, wound bottom, presence of cavity with tendons and/or bone formations may be recognized therein, characteristics of exudate (smell, color), pain sensation. In control group there were included 81 apparently healthy subjects. All groups contained age- and sex-matched subjects. Phenotyping of peripheral blood B cells was performed by using flow cytometry with panel of monoclonal antibodies. It was found that count of B cells in patients did not change in parallel with increased total lymphocyte count, but was associated with their functional activity (increased percentage of CD23- and CD38-positive B cells). Moreover, percentage of B1 and naive B2 cells declined in patients with pressure ulcers that seemed to be associated with the premorbid background of the main disease, lack of adequate wound healing process coupled to tissue necrosis and damage to skin capillaries. The more severe the clinical course of pressure ulcers (regarding area and stage of development), the smaller percentage of B2 cells (both naive and memory B cell subsets) was detected in the patient peripheral blood. At the same time, changes in the B cell phenotypic profile from patients are associated with the area of lesion, but not with the stage of developing pressure ulcers evidencing that B cells affect healing of pressure ulcers. The features of B cell phenotype promote unfavorable disease outcome evidenced by the lack of quantitative differences in B cell lineage composition or level of surface expression for activation markers.

Russian Journal of Immunology. 2020;23(4):419-428
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Serum macrophage colony-stimulating factor levels in patients with essential hypertension after SARS-CoV-2 infection

Radaeva O.A., Simbirtsev A.S., Selezneva N.M., Iskandyarova M.S.


Understanding changes in the cytokine-mediated mechanisms in immunopathogenesis of essential hypertension (EH) after COVID-19 poses a pressing scientific issue. SARS-CoV-2 exerts direct effects on macrophages with high probability altering regulatory M-CSF-VEGF-A-IL-34 axis, thereby accounting for change in cytokine-mediated patterns of hypertension progression. Immunopathogenesis of complications after SARS-CoV-2 infection and a role of M-CSF in EH pathogenesis justify study objective – to compare the serum M-CSF and VEGF-A, IL-34 levels in stage II EH patients prior to COVID-19 and one month after recovery to assess modality of altered M-CSF-mediated mechanisms behind hypertension progression. Four groups of patients were stratified depending on EH and clinical characteristics of COVID-19 (without/with pneumonia). Blood sampling was performed one month after COVID-19. The serum M-CSF and VEGF-A, IL-34 level was measured by using enzyme-linked immunosorbent assay. The data were statistically processed by using Stat Soft Statistica 13.5. Comparative analysis of serum M-CSF level in patients with stage II EH prior and after COVID-19 revealed that regardless of clinical course (with/without pneumonia) they were featured with higher levels of M-CSF one month after recovery (p < 0.001) vs baseline level. The serum VEGF-A level in patients with stage II EH did not change in papallel with increased M-CSF (458 pg/ml or more) one month after SARS CoV 2 infection. However, M-CSF stimulated rise in serum VEGF-A level and accounted for formation of marked coronary collateral network prior to infection. A relationship between the increased serum M-CSF level (higher than 392 pg/ml) and elevated percentage of COVID-19 with pneumonia in patients with stage II EH prior to the infection might be related to the hypothesis about “a role of dysregulated activation of mononuclear phagocytes in development of lung tissue damage”. The data presented prove scientific and clinical value of assessing a role for M-CSF with respect to altered cytokine-mediated patterns of EH progression after COVID-19 recovery.

Russian Journal of Immunology. 2020;23(4):429-436
pages 429-436 views

Relation between TNFα and S100B in patients with herpes zoster and postherpetic neuralgia

Knysh S.V., Nevezhkina T.A., Kostyushko A.V., Ilyina P.S.


One of the most important components in the pathogenesis of herpes zoster and postherpetic neuralgia is presented by disturbed neuroimmune interaction, characterized by development of chronic inflammation in the nervous system structures. Normally existing interaction between immune and nervous systems is altered and results in development of pathological system. Altered level of TNFα and S100B proteins may characterize the features of neuroimmune inflammation during herpes zoster infection. Objective: to assess a relationship between TNFα and S100B level in patients with herpes zoster and postherpetic neuralgia. We examined 106 patients with herpes zoster within the framework of our study. Based on assessing intensity of pain syndrome and its three-month follow-up data after primary treatment patients were subdivided into 3 main groups: group I – weak or moderate pain syndrome; group II – severe pain syndrome; group III – postherpetic neuralgia. The control group contained 30 age-matched apparently healthy volunteers. Venous blood sampling was performed twice: on day 1 and day 10 after disease onset. Biological material in control group was collected once. Level of blood serum TNFα and S100B was measured by using solid-phase enzyme immunoassay (ELISA) on analyzer “Multiscan”. While assessing TNFα level in all three main groups, its lowered level was detected (p < 0.05) on day 1, without finding inter-group differences. On day 10 after disease onset, level of TNFα did not differ from the control values found in groups I and II, while in group III it remained lowered, not being significantly differed from those found on day 1. Level of S100B in the blood serum in patients vs. control group was equivalently increased (p < 0.05), showing no inter-group differences. On day 10, the level of S100B in the blood serum from patients of groups I and II tended to stabilize, by decreasing almost by 2-fold to reference intervals in group I, without reaching control values, in group II. Patients from group III were found to have serum level of S100B remained elevated compared to control group without dynamic changes between 1 and 10 days. A correlation analysis for TNFα and s100b protein revealed significant feedback relation between them (p < 0.05) in group III.

Russian Journal of Immunology. 2020;23(4):437-442
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IL17A rs2275913 gene polymorphism in Uzbek ethnic group and its linkage with development of allergic rhinitis

Dustbabaeva N.D., Irsaliyeva F.K., Nurmatova N.F., Baybekova V.F., Aydarova N.P., Akhmedov K.S.


Currently, new insights into the general mechanisms of developing allergic diseases suggest that Th17 cells are involved in the pathogenesis of allergic rhinitis characterized by dominant production of cytokines IL-17A and IL-17F. Objective: to assess IL17A rs2275913 gene polymorphism in the Uzbek ethnic group and its linkage with development of allergic rhinitis. There were examined 83 patients with allergic rhinitis, among which 38 (46%) had intermittent form and 45 (54%) – with persistent disease form. In control group there were included 123 apparently healthy subjects. Genotyping of IL17A rs2275913 polymorphism was carried out by using real-time polymerase chain reaction (Real-Time) “SNP-EXPRESS”-RV.
While analyzing frequency distribution of the G and A alleles within the IL17A gene, it was found that the A allele dominated (38.7% vs 19.5%, respectively, χ2 = 15.9; p < 0.05). The G/G genotype in the A/G IL17A gene polymorphism was much less abundant in AR patients compared to apparently healthy patients in control group. It was detected increased frequency of heterozygous G/A allele within the IL17A gene in AR patients vs. control group (56.9% vs 30.2%, respectively, χ2 = 11.9; p < 0.05; OR = 3.1). While comparing the A/A genotype of the IL17A gene it was shown that its prevalence was significantly higher in AR patients compared to healthy subjects (14.1% vs 5.9%, respectively, χ2 = 4.6; p < 0.05).
Our findings demonstrated that the AA genotype in the IL17A rs2275913 gene is associated with developing AR in the Uzbek ethnic group. Such trait may be used as AR predictor, provide valuable information for design and implementation of pathogenetically justified methodological approaches to therapy and prevention of allergic rhinitis.

Russian Journal of Immunology. 2020;23(4):443-448
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IL17A rs2275913 polymorphism and features of immunological parameters in patients with persistent allergic rhinitis during allergen-specific immunotherapy

Irsalieva F.K., Dustbabaeva N.D., Kamalov Z.S., Ziyadullaev S.K., Nurmatova N.F., Akhmedov Z.K.


Allergic rhinitis (AR) represents a global healthcare challenge. Epidemiology data demonstrate that around 20% of all-age group subjects suffer from allergic rhinitis. Over the last decades, AR incidence and morbidity have been markedly increased due to poorly understood causes. For instance, in the last decade AR prevalence has been elevated by 2-fold in Uzbekistan. However, medical records related to AR prevalence based on patient visit rate infer that it is dozens of times lower than actual data and reflects in no way severity of the problem, but sufficient enough to outline its large-scale spread. Allergen-specific immunotherapy (ASIT) requiring further development and adjustments represents one of the most promising approaches to treat allergic diseases. Some researchers note rise in respiratory tract allergic disease (AD) prevalence including caused by pollen allergens. Therapeutic interventions in this type of pathology emerging due to chronic inflammatory process mainly in airway mucosa are aimed at achieving good control over disease symptoms, lowering risk of subsequent exacerbations and preventing AD aggravation. IL-17 belongs to the Th17 cell-derived cytokines that was described relatively recently. IL17 genes encode six proteins (molecular weight 20-30 kDa), among which IL17A and IL17F display peak sequence homology and were studied in numerous cell types. IL-17 family proteins take part in various reactions of immune response being mainly secreted by Th17 cells. It was shown that immunological mechanisms particularly mediated by cytokines such as IL-17A involved in inflammation, regeneration and fibrogenesis are crucial in progression of diverse infectious diseases.

Russian Journal of Immunology. 2020;23(4):449-460
pages 449-460 views

Assessing prevalence and clinical and allergological characteristics of fungal sensitization in Samara City

Mazokha K.S., Manzhos M.V., Khabibulina L.R., Aseeva E.V., Seleznev A.V.


Molds Alternaria spp., Cladosporium spp., Aspergillus spp., and Penicillium spp. play a major role in populational sensitization. Fungal spores may become a predisposing factor in developing bronchial asthma (BA), allergic rhinitis (AR) and atopic dermatitis (AD). The aim of our study was to investigate prevalence and clinical manifestation of fungal sensitization in the City of Samara. 2016 – 2019 general clinical and allergological examination of 855 patients of different age suspected for respiratory allergy was performed. All patients were tested for measuring serum level of total IgE and IgE specific to most common respiratory and food allergens, including fungal allergens derived from Alternaria spp., Cladosporium spp., Aspergillus spp., Penicillium spp., (RIDA Allergyscreen, R-Biopharm, Germany). 26 patients previously diagnosed positive to native Alternaria extracts and 50 patients with symptoms of exacerbated allergic rhinitis during summer and autumn were tested for serum level of IgE specific to recombinant molecular Alternaria component (rAlt a l, Phadia ImmunoCAP). It was found that 28.4% pediatric and 18.2 % adult patients (р = 0.0322). 25% of patients appeared to be sensitized to fungal allergens. Sensitization to various mold-derived allergens was distributed as follows: Alternaria allergens – in 23% all patients examined, (27% children and 14% adults); Cladosporium – in 11% patients (10% children and 8% adults); Aspergillus – in 5% patients (6% children and 2% adults); Penicillum – in 2% patients (1% children and 3% adults). Moreover, sensitization to Alternaria allergens prevailed in more than 90% patients with fungal sensitization that was more common in young individuals (up to 18% in 7-17-year-old group), but profoundly declined in subjects over 50 years of age (p = 0.00001, χ2 = 61.31). True sensitization to Alternaria (Alt a 1) was detected in more than half (63%) of patients with confirmed sensitization to native Alternaria extracts, whereas 66% and 25% patients with fungal sensitization suffered from allergic rhinitis and asthma, respectively. Sensitization to Alternaria is a risk factor of developing asthma in childhood (OR = 2.415). The data obtained evidence about prevalence of fungal sensitization and associated allergic diseases in the Samara region.

Russian Journal of Immunology. 2020;23(4):461-466
pages 461-466 views

Sensitization to inhalation allergens in patients with psoriasis and atopic dermatitis

Barilo A.A., Smirnova S.V.


Psoriasis is an autoimmune chronic inflammatory disease that affects various body organs and systems, mainly targeting the skin. In recent years, an association of autoimmune diseases with atopy has been actively debated. The published data aimed at examining relationship between atopy and psoriasis are very scarce and highly contradictory that account for importance of our study. Generation of transcutaneous sensitization due to potential invasion of allergens across impaired epidermal barrier in psoriasis is of special interest. We aimed at investigating a range of sensitization to pollen, fungal and indoor allergens in patients with psoriasis and atopic dermatitis and comparatively analyze our data. There were enrolled patients with psoriasis vulgaris (group 1, n = 27) aged 18 to 67 years (mean age 41.0±3.1 years). The comparison group consisted of patients with atopic dermatitis (group 2, n = 41) aged 18 to 57 (mean age 28.0±1.5 years). Allergen-specific examination was carried out (collection of allergic history, determining sensitization). Skin prick testing was performed by using standardized allergens (Allergopharma, Germany). Statistical data were analyzed by using the Statistica 6.0 software package. While conducting a comparative analysis regarding a range of sensitization to pollen allergens, it was found that sensitization to tree and weed pollen in patients with atopic dermatitis vs psoriasis was observed at significantly higher rate. Sensitization to indoor allergens in patients with atopic dermatitis vs psoriasis tended to increase. More than half of patients with psoriasis revealed sensitization to pollen derived from meadows, weeds, grasses and trees. Sensitization to Candida albicans tended to rise in patients with psoriasis vs atopic dermatitis. Moreover, we found that patients with psoriasis exerted much higher sensitization to Candida albicans, Cladosporium herbarum and indoor allergens was revealed. Hence, presence of damaged epidermal barrier in psoriasis likely contributes to increased invasion of inhalation allergens and formation of percutaneous sensitization. Therefore, further investigation of features related to the range of sensitization to various allergen groups in psoriasis seems promising and may lead to discovery of new therapeutic targets.

Russian Journal of Immunology. 2020;23(4):467-472
pages 467-472 views

Examining sIgE-profile in patients with ambrosia allergy in Samara

Zhukova N.N., Manzhos M.V., Seleznev A.V.


It is considered that Ambrosia trifida is not widespread in Russia, thereby avoiding its threatening effects to populational health. However, there are some areas in Russia where more than half of land area is covered by Ambrosia trifida. Many such foci are found in the Samara, Orenburg regions, Tatarstan and Bashkiria. Ambrosia trifida is distributed in Central Russia, the North Caucasus region and Siberia.
The objective of the study was to examine specific IgE-profile in ragweed sensitized patients in the Samara region. A clinical and allergy examination of 969 patients with allergic rhinitis was performed. Allergic diagnostics was performed by using skin testing (prick-test) with standard set of pollen, household, and epidermal allergens. The data of skin tests in patients co-sensitized with ragweed and Artemisia allowed to analyze IgE-antibodies specific to the major Ambrosia (Amb a 1, Аmb. trifida) and Artemisia (Art v 1) allergens. Patients with negative skin test for the Amdrosia artemisiifolia and clinical manifestations of seasonal allergy were assessed for level of sIgE-antibodies nAmb a 1 and Amb trif.
Skin test data demonstrated that seasonal and combined forms of allergic rhinitis dominated in patients examined. In particular, positive skin test data for pollen allergens dominated (50.6%) among all allergen groups so that more than half of them belonged to weed pollen allergens. Patients challenged with skin tests for Artemisia and ragweed allergens more likely displayed positive reaction to the Artemisia allergen (71.27%) and Ambrosia artemisiifolia (50.88%).
Co-sensitization (to Artemisia and ragweed) prevailed in this geographic region featured with equal rate of simultaneously detected sIgE specific to the two types of ragweed and artemisia (nAmb a 1 + nArt v 1 + Amb trif) as well as Ambrosia trifida and Artemisia (Amb trif + nArt v 1). Almost half of the patients with negative Ambrosia art. prick-test were found to bear sIgE specific to Amb trif. Further investigation will help to better understand this phenomenon and take a fresh look at diagnostics and treatment of ragweed allergy in relevant geographic area.

Russian Journal of Immunology. 2020;23(4):473-478
pages 473-478 views

Examining dynamic changes in the complement system components and immune complexes of various fractions in adolescents with obesity and metabolic syndrome affected by antihypoxants

Kukina G.N., Kiryukhina S.V., Labunsky D.A., Kolmykov V.A., Yurasova E.Y., Boyarkin E.V.


In this paper, we consider a relation between adolescent obesity and dynamic changes in the complement system components and immune complexes of various fractions affected by antihypoxants, because obesity is one of the most common non-communicable diseases worldwide and rises an interest for many researchers. New studies emerge revealing an imbalanced immune system that aggravates upon obesity and affects multiple immune processes, as well as increasing interest in studying obstructive sleep apnea syndrome resulting in tissue hypoxia, thereby increasing a risk of cardiovascular diseases. Our study allowed to detect metabolic syndrome in 89% of obese patients (groups 1 and 2) and 25% of adolescents with normal body weight (control group 2). We analyzed the complement components and circulating immune complexes of various fractions and revealed positive dynamics of the examined parameters due to combination therapy with the anti-oxidant Mexidol and hyperbaric oxygenation, which may indicate that oxygen-dependent neuroimmune mechanisms might be involved in the pathogenesis of metabolic syndrome in obesity. Such systemic activation of regulatory mechanisms for maintaining homeostasis is necessary for formation of biologically active thymusderived serum factor ensuring lymphocyte differentiation, i.e. pathogenetic therapy corrects dysregulatory impact of traditional therapy for obesity and optimizes immune responses. During the study we observed that the combination treatment using Mexidol and HBO resulted in better recovery of clinical functions and immune responses, and that such therapy exerted a positive effect on dynamics of patient mental activity. We believe that such therapeutic effects were due to antioxidant and antihypoxic activity of the applied pharmacological drugs. We also found that obese children are featured with metabolic syndrome and predisposed to developing relevant complications. Hence, for early diagnostics of metabolic syndrome it is necessary to study children with normal body weight that will allow to diagnose metabolic changes at earlier stage, because changes in blood biochemical parameters such as triglycerides, very low-density lipoproteins, glycemia levels etc. occur long before initial changes in person appearance might emerge.

Russian Journal of Immunology. 2020;23(4):479-486
pages 479-486 views

Ultrasound criteria of splenomegaly in patients with fever and infectious mononucleosis

Perepelitsa S.A., Perminova L.A., Stepanyan I.A., Zakhar E.V.


Ultrasound examination of the spleen is a promising approach allowing to accurately determine its normal size in various age groups as well as in pathological conditions. Objective – to evaluate spleen size changes in patients with febrile state and infectious mononucleosis. Ultrasound morphometric examination of the spleen was carried out in patients with febrile state (group “A”, n = 22) and infectious mononucleosis (group “B” n = 24) by assessing organ echo structure, contour clarity, and its uniformity. Morphometric data allowed to measure spleen weight and various coefficients by using the method proposed by Vozgoment et al. for calculating spleen weight (Wt) with formula: Wt = 0.34 * L2h, where L – the length of the spleen, h – the thickness of the spleen (cm); spleen weight coefficient (SWC) by using the formula: 1000 m / body weight (in grams), where m – the mass of the spleen; spleen weight-to-body height ratio (KI) by using the formula: spleen weight (g) / height (cm); spleen weight-to-body surface area ratio (Ks) by using the formula: spleen weight (g) / body surface area (m2). Statistical analysis was performed by using Statistica 10.0 software package. Febrile state in most cases is not accompanied by changes in spleen size. However, decreased spleen size was found in one (4.5%) patient aged 58 years, whereas splenomegaly – in 2 (9%) cases (SWC range 5.5- 5.9) in young patients aged 18 and 25 years. The course of infectious mononucleosis in 25% cases was not accompanied by change in spleen size. In other cases, both decreased (20.8%) and increased (54.2%) spleen size were observed. In particular, decreased spleen size was detected in patients with average age of 43.6±14.5 years, whereas increased spleen size (SWC range 4-8.9) was typical for young people aged 25±8 years. Febrile state in most cases is not paralleled altered spleen size. Infectious mononucleosis was associated with the three types of altered spleen size: no change, decreased spleen size characteristic to older patients, or increased spleen size observed in young subjects. Ultrasound examination of the spleen with measuring its morphometric parameters represent objective criteria allowing to fully assess the state of this immune organ and reveal degree of its involvement in the pathological process at the preclinical level.

Russian Journal of Immunology. 2020;23(4):487-492
pages 487-492 views

Body sensitization to various antigens in children with chronic hepatitis B and concomitant giardiasis

Nurmatova N.F., Mirsalikhova N.K., Asilbekova M.А., Irsalieva F.K., Dustbabaeva N.D., Akhmedov J.K.


The aim of the study was to evaluate body sensitization by measuring antigen-binding lymphocytes specific to various antigens in children with chronic hepatitis B and intestinal giardiasis.
The study of ASL was carried out in 126 children with CHB and 30 apparently healthy children aged 4 to 14 years. Among children with CHB, 93 had confirmed intestinal giardiasis (group I), and the remaining 33 were patients without lambliasis (group II). Sensitization and an autoimmune process were detected by assessing activity of specific immunity parameters such as ASL amount by indirect rosette formation against HBsAg, G. lamblia and intestinal tissue. We found that intensity of disease activity and ASL level against the examined antigens were paralleled evidencing about sensitization and autoimmune reactions related to giardiasis invasion in children with CHB. Depending on the duration of CHB with lamblial invasion ASL study data showed that prolonging disease duration resulted in lowered ASL to HBsAg peaking upon disease lasting up to 3 years. Apparently, it might be accounted for by body mobilization fighting against infection in general biological sense, and their further decline may occur due to host adaptation to increased antigenic load. The amount of ASL to the intestinal tissue was also somehow related with duration of the disease. The data obtained indicate increased self-sensitization along with increased duration of the disease. Similar data were obtained while studying amount of ASL to G. lamblia, thereby confirming a role of sensitization and self-sensitization in pathogenetic mechanisms of the developing CHB with giardial invasion especially during long-term course. Thus, the course of CHB with lambliasis invasion is accompanied by reaction of specific immune arm. Rise in amount of ASL to HBsAg, intestinal tissue and G. lamblia occurs along with deteriorating degree of disease activity and duration of hepatic disease suggesting about importance of sensitization and self-sensitization in pathogenesis of CHB development with giardiasis invasion, aggravating the course and outcome of the disease. The data reliability allows to conclude that giardiasis infection and prolongation of both hepatic pathological process and entire infectious process in children with CVH are directly interconnected. These data clearly underscore importance of timely eradication of G. lamblia upon liver damage. At the same time, administration of specific drugs (scheme) should be performed by taking into account its hepatotoxicity, bioavailability and effectiveness.

Russian Journal of Immunology. 2020;23(4):493-498
pages 493-498 views

Primary immunodeficiency masks: A clinical case of vaccine-associated paralytic poliomyelitis

Savin T.V., Kuznetsova R.N., Kuznetsova A.A., Totolian A.A.


Human inborn immune-related errors comprise a heterogeneous group of rare genetically determined diseases of the immune system caused by loss or gain of function mutations altering relevant protein functions. The 2019 International Union of Immunological Societies recently proposed the classification for such pathologies now comprising 406 distinct disorders with 430 different gene defects. Predominantly antibody deficiencies represent most common group of human inborn immune-related errors, which diagnostics poses uneasy challenge for general practitioner due to a broad range of their clinical manifestations, such as infection, allergy, autoimmunity and malignancy. In addition, patients with human immune-related inborn errors may develop a vaccine-associated disease after administering live vaccines in accordance with the Russia-wide National Vaccine Schedule. Most common among vaccine-associated diseases are vaccine-associated paralytic poliomyelitis, vaccine-associated encephalitis (1 case per 1 000 000 doses of measles, rubella, varicella vaccine), vaccine-associated meningitis (1 case per 250 000 – 500 000 doses of mumps vaccine) as well as adverse effects related to BCG immunization: local (infiltration, cold abscess – 8.6 case per 100,000 vaccinated patients) and disseminated complications (BCG lymphadenitis – 15.5 case per 100 000 vaccinated patients, BCG osteitis – 3.5 case per 100 000 vaccinated patients). Vaccine-associated paralytic poliomyelitis in vaccinated patients occurs after the first, second and rarely third oral polio vaccine dose inoculation. Incidence rate for vaccineassociated paralytic polio after 1 and 3 oral vaccine inoculation ranges from 1 case per 700 000 vaccine doses to 1 case per 3 500 000, respectively. Vaccine-associated paralytic poliomyelitis mainly emerges due to inborn mutations related to humoral immunity after primary vaccination with oral polio vaccine or close contact of unvaccinated patients with subjects vaccinated with oral polio vaccine. Here, we describe a clinical case of vaccine-associated paralytic poliomyelitis in patient with primary immunodeficiency. Our is aimed at emphasizing importance of immunological alertness with regard to detecting primary immunodeficiencies and timely apply a replacement therapy prior to verifying type of immunodeficiency.

Russian Journal of Immunology. 2020;23(4):499-504
pages 499-504 views

Retrospective analysis of pediatric primary immunodeficiencies with congenital heart defects

Deryabina S.S., Cheremokhin D.A., Tuzankina I.A., Bolkov M.A., Shinvary K.


Around 20,000 children with heart defects are born annually in the Russian Federation, among which around 5,000 children are manifested by its critical course that requires surgical correction within the first days after birth. Although timely pre- and postnatal diagnostics of congenital heart pathology allows to provide proper therapeutic and surgical assistance for such patients, it is hard to minimize severe complications at any stage of the child’s treatment. Quite often, post-surgery patients are unable to cope with serious complications caused by infectious diseases of the respiratory tract, endocardium and meninges. A special place is taken by cases of severe postoperative period: long-term non-healing postoperative wounds and septic disorders leading to patient death. Here we put forward an idea that congenital heart disease may serve as a marker of primary immunodeficiency characterized by lowered parameters of cellular and humoral immunity. Current retrospective study included 29 children died within the first year of life, whose medical records demonstrated confirmed congenital heart disease and manifested signs of immune-dependent pathology. There were analyzed data regarding pregnancy course in order to identify factors contributing to early diagnostics of immune-related pathology associated with CHD. The analysis of existing problems affecting proper diagnostics and treatment of children with congenital heart disease coupled to “covert” PID form was performed. It was noted that among twenty described syndromes manifested with congenital heart disease, seven are currently referred to the group of primary immunodeficiencies. Types of congenital heart defects in the study group ranged from disorders of the valve apparatus to the non-functional opening between heart chambers. Signs of immune-related pathology included decreased thymus size revealed by ultrasound examination as well as lowered value of genetic markers TREC and KREC, retrospectively obtained from neonatal dry blood spots. Finally, we name a key element for successful differential diagnostics of PID with congenital heart disease – awareness of various medical workers about such pathology for developing algorithms for their interaction with regard to management of such comorbid patients.

Russian Journal of Immunology. 2020;23(4):505-514
pages 505-514 views

Dynamics of innate immunity parameters in acute kidney injury after coronary artery bypass grafting

Markelova E.V., Fomina O.I., Arsenina V.Y.


Acute kidney injury (AKI) developing after cardiac surgery remains unsolved issue despite the high level of surgical techniques as well as organ and tissue protection during artificial blood circulation. Various publications demonstrate that complications emerge in as many as 42% cases, whereas renal replacement therapy is required in up to 1-8% cases. Systemic inflammatory response syndrome and activation of the blood coagulation system largely underlie developing AKI finally resulting in acute renal failure. Release of large amounts of cytokines is associated with subclinical renal damage, primarily with blocking renal glomerular filtration. Measuring concentration of serum inflammatory markers that could reflect activity of inflammatory events is crucial for predicting and selecting treatment methods as well as for identifying predictors of severe course with opportunity of early onset renal replacement therapy after hospitalization. Objective of our study was to assess diagnostic and prognostic value of innate immunity parameters such as interleukin (IL) 6, 8, 10, 17, tumor necrosis factor alpha (TNFα), growth factor TGF-β1 in patients with acute kidney injury before and after CABG. Blood serum samples collected from 120 patients (males and females) with ischemic heart disease (IHD) were examined before and after CABG. It was found that patients with acute kidney injury had elevated serum level of cytokines IL-6, IL-8, IL-10, IL-17, TNFα, and TGF-β1 in all groups on day 1 and day 2 after surgery. Hence, we provided the data on more detailed investigation of immune alterations in cardiosurgical patients with AKI prepared for planned CABG.

Russian Journal of Immunology. 2020;23(4):515-522
pages 515-522 views

Personalized algorithm of immunocorrection with intravenous immunoglobulins for preventing and treating complications of burn disease by comprehensively analyzing immune status

Kozlova M.N., Zemskov V.M., Shishkina N.S., Barsukov A.A., Demidova V.S., Alekseev A.A.


Intravenous immunoglobulin preparations with proven effectiveness are widely used for treatment of various immunodeficient, autoimmune, inflammatory and infectious diseases. Nevertheless, algorithms for use of immunoglobulin preparations to correct immune status in burn disease, prevention, etc. have not been developed yet. Here we present the results of a prospective controlled study with 70 patients assessing effectiveness of using immunoglobulin preparations for intravenous administration in complex treatment of subjects suffering from extensive burns. Expanded immunological examination (more than 300 studies) in this patient cohort at different stages of burn disease consisted of phenotyping lymphocytes, granulocytes, monocytes (constitutive and activation markers, cell functional activity), immunoglobulin level and phagocyte oxygen metabolism. Data analysis included significant parameters only. Patient selection for using intravenous immunoglobulins to prevent or treat septic complications was performed by using the previously proposed 95%-specificity sepsis prognosis formula: LF < 9.3%, NK cells < 5%, HLA-DR+ Mn < 50%, IgG < 4.0-6.0 g/l, LII > 4.0 u, CD64+ Gy > 90-100%, N/I NF > 21%. Immunosuppressive therapy with drug “GabriglobinIgG” at a dose of 50 ml per day for preventing infection spread in patients with burns for 5 days as well as for treatment of sepsis for 10 days, exerted pronounced immunomodulatory effect compared to control groups not only restoring baseline IgG deficiency, but also normalizing quantitative deficit of key immune parameters such as total lymphocytes, B and T cells, natural killer cells, cytotoxic T lymphocytes. Use of gabriglobin for sepsis prevention was effective in 72% of cases (control group without gabriglobin – 37%), so that clinical and immunological effectiveness was as high as 79% (control group – 32%). At the same time, along with conventional immune indicators in heavily burned patients, immune markers previously underestimated were: CD56+ and CD25+ monocytes, CD14+ and CD40+ granulocytes, CD40+ lymphocytes (B cell subset), various effector and regulatory natural killer subsets. It allowed to obtain radically new information about immune system state, inflammation, and bacterial complications in heavily burned patients and apply a personalized approach for immunocorrection by using several intravenous immunoglobulin preparations for effective comprehensive treatment of burn injury-related consequences.

Russian Journal of Immunology. 2020;23(4):523-528
pages 523-528 views

Features of altered immune status in acute brain concussion

Norka A.O., Vorobyev S.V., Kuznetsova R.N., Serebriakova M.K., Kudryavtsev I.V., Kovalenko S.N.


Traumatic brain injury (TBI) is one of the most common type of injuries, so that its mild form prevails in overall injury pattern. Currently, it is known that brain injury triggers immune system response, but its role in translating into clinical manifestations, potential complications and sequelae remains poorly understood. It necessitates assessment of cellular immunity in patients with acute TBI of varying severity followed by investigating relationship between identified changes. It is now believed that immune system plays a lead role in brain functioning. It may be accounted for by interplay between peripheral immune cells and the brain, which may become augmented during developing immune response.
Here we quantitatively assessed composition of major peripheral blood helper T cell subsets in TBI patients by flow cytometry measuring percentage of central (CM, CD45RA-CD62L+) and effector (EM, CD45RA-CD62L-) memory Th cells. It was found that percentage of Th17 (CXCR5-CXCR3-CCR6+CCR4-), DP Th17 (CXCR5-CXCR3+CCR6+CCR4+) within CD3+CD4+T cell population were significantly increased (p < 0.05) compared to control group. Moreover, percentage of Th1/Th17 subset (CXCR5-CXCR3+CCR6+CCR4-) was significantly increased (p < 0.05) within EM and CM T cell subsets compared to control group. In addition, percentage of Th1 (CXCR5-CXCR3+CCR6-CCR4) was also significantly elevated in CD3+CD4+, EM and CM T cells compared to apparently healthy subjects. Hence, the data obtained allow to consider immune reactions among crucial arms in TBI pathogenesis related to concussion and its consequences. Thus, brain concussion affects cellular immune response triggering distortion in CD3+CD4+T cell composition as well as percentage of helper central and effector memory T cells.
Hence, the changes revealed in patients with acute brain concussion may predetermine disease course and developing long-term complications, which requires advancing therapeutic and rehabilitation protocols in such patients.

Russian Journal of Immunology. 2020;23(4):529-536
pages 529-536 views

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