Vol 24, No 4 (2021)

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Personalized approach to diagnostics and therapy of patients with psoriasis

Barilo A.A., Smirnova S.V.


Establishing causal relationship between allergy and psoriasis and determining appropriate sensitization profile may guide clinicians in terms of specific allergological diagnostics and personalized therapy. Our purpose was to study the occurrence of food allergy and certain sensitization profile to food allergens in patients with psoriasis, in order to establish new approaches to specific diagnosis and treatment of the disorder.
The study involved patients with psoriasis vulgaris (n = 51) aged 18 to 66 years. The control group included practically healthy people matched by sex and age (n = 19). All the patients underwent allergological examination: collection of allergic history, determination of total immunoglobulin E (IgE) and eosinophilic cationic protein concentration in blood serum by means of indirect immunofluorescence analysis using Thermo Scientific Multiskan FC semi-automatic analyzer. The sensitization profiles to food and pollen allergens were also studied. Calculation and analysis of these data was carried out using Statistica 8.0 software package.
Concentration of total immunoglobulin E in blood serum in the group of patients with psoriasis was 57.9 IU/ml (31.6-135.1) compared to control group, with 45.1 IU/ml (23.4-144.0). The levels of serum eosinophilic cationic protein was 8.6 ng/ml (4.6-20.3) in the patients with psoriasis, being 7.9 ng/ml (4.6-27.1) in controls. When studying the spectrum of sensitization to food allergens in patients with psoriasis, some specific features were revealed. E.g., sensitization to cow’s milk was detected in 33.3% (n = 17); to beef, in 39.2% of cases (n = 20), to whole chicken egg – 29.4% (n = 15), to chicken, in 39.2% (n = 20); to wheat flour, 37.2% (n = 19); to rye flour, in 31.4% (n = 16); to rice and buckwheat, 21.6% (n = 11), to yeast, in 23.5% of the patients (n = 12). Upon administration of individual elimination diet for 1 month, we observed a decrease or complete regression of itching, decreased severity of infiltration, hyperemia and peeling in the foci of psoriatic skin lesions in 68% of the cases. Normal concentration of total immunoglobulin E and eosinophilic cationic protein in blood serum of patients with psoriasis combined with positive results of skin-prick tests and elimination effect presumes a participation of non-atopic immune pathologies when triggering allergy in psoriatic disease.

Russian Journal of Immunology. 2021;24(4):455-460
pages 455-460 views

Peripheral molecular messages – cytokines and stress hormones – in the context of cognitive aging phenotypes: healthy ageing/depression/dementia

Burmistrova A.L., Cazaux M.E., Alekseeva A.S., Filippova Y.Y.


Over last years, the world’s aging populations are rising rapidly, and the phenotypes of cognitive insufficiency, such as old age, depression and dementia, are increasing. Search for approaches to discrimination between such phenotypes is extremely relevant. Current studies present compelling evidence of the key role of immune system (its peripheral compartment), and the stress response system in physiological brain health. Therefore, assessment of complex interactions between immune and neuroendocrine systems may be an effective way to differentiate between depression and early stages of dementia in elderly people. Our purpose was to reveal peripheral molecular messages, e.g., cytokines and stress hormones, in the context of cognitive impairment phenotypes: healthy old age/old age depression/dementia. Eighty elderly people were included into groups as follows: “Healthy ageing”, “Dementia”, “Depression”. Levels of certain cytokines: IL-6, IL-1β, TNFα, IFNγ, IL-10, and stress hormones (cortisol, ACTH, dopamine, noradrenaline, and adrenaline) were determined in blood plasma by ELISA. The intergroup differences were evaluated by the Kruskal-Wallis test with Conover-Inman post-hoc pairwise comparisons. For differential diagnostics between the groups of elderly people with varying grades of cognitive impairment, we used linear canonical discriminant analysis performed on the ranks. It has been shown that cognitive insufficiency phenotypes—old age depression and dementia—differ from the healthy ageing phenotype with their high peripheral levels of TNFα cytokine and low levels of IL-1β. The differences between depression in elderly and dementia included lower level of IL-10 in depression (lower than in “Healthy ageing”), and high IL-6 in dementia (compared to “Healthy ageing”). Evaluation of the hypothalamic-pituitary and sympatho-adreno-medullary axes hormones showed hyporesponsiveness of hypothalamic-pituitary axis, regardless of cognitive insufficiency phenotypes, along with activation of sympatho-adreno-medullary axis, i.e., high dopamine level in old age depression with dementia, and high adrenaline level in dementia, than in depression of elderly phenotype and healthy ageing. Such significant differences in the levels of molecular messages, i.e., cytokines and stress hormones among the old age person groups, enabled diagnostic efficacy of 87.5% to differentiate cognitive phenotypes of aging: healthy ageing, old age depression, and dementia.

Russian Journal of Immunology. 2021;24(4):461-468
pages 461-468 views

Gene polymorphism of IL6, DHCR7, VDR, CYP2R1, GC in polycystic ovary syndrome and autoimmune thyroiditis

Valikova O.V., Zdor V.V., Sarychev V.A.


Polycystic ovary syndrome is a common pathology in women of reproductive age, leading to hyperandrogenism, dyslipidemia, diabetes mellitus, ovulation disorder and infertility. Etiopathogenesis of the disease is actively studied, but many of its mechanisms are unclear. The aim was to study the frequency of IL6 and vitamin D receptor gene polymorphisms, blood contents of vitamin D in polycystic ovary syndrome combined with autoimmune thyroiditis.
A total of 192 women were examined, the average age of the patients was 25.5±3.1 years; of these, 130 women had polycystic ovary syndrome. The patients were divided into 2 groups: with polycystic ovary syndrome combined with autoimmune thyroiditis (1st group) and olycystic ovary syndrome without autoimmune thyroid pathology (2nd group); 62 healthy women made up the control sample. The ELISA method was used to determine thyroid stimulating hormone, thyroid hormones, antibodies to thyroid peroxidase, vitamin D, testosterone, estradiol, progesterone, 17-hydroxyprogesterone, luteotropic hormone, follicle-stimulating hormone. Material for genetic studies was isolated from buccal cells. The typing was performed by PCR, and the following polymorphisms were tested: IL6 (rs1800795 SNP), vitamin D receptor (VDR) gene (rs1544410), DHCR7 (rs12785878), GC (rs2282679), CYP2R1 (rs10741657). The results were as follows: polymorphism of IL6, VDR, DHCR7, GC, CYP2R1 genes was revealed in the patients with polycystic ovary syndrome in combination and without concomitant autoimmune thyroiditis. The lowest levels of 25-hydroxyvitamin D in serum were found in the patients with polycystic ovary syndrome and autoimmune thyroiditis.
Polymorphism of IL6 genes, vitamin D receptor, DHCR7, GC, CYP2R1 genes may aggravate the course of polycystic ovary syndrome and requires a more comprehensive study. When polycystic ovary syndrome was combined with autoimmune thyroiditis, the studied gene polymorphisms did not differ significantly from those in patients with polycystic ovary syndrome without autoimmune thyroiditis, thus suggesting greater significance of these genetic factors in pathogenesis of polycystic ovary syndrome. However, more than a half of women with combined endocrine disorders had both homozygous and heterozygous variants of pathological IL6 gene carriage along with lowest vitamin D levels, which may significantly affect immune response and, hence, determine the development of both endocrine disorders.

Russian Journal of Immunology. 2021;24(4):469-476
pages 469-476 views

Production of growth factors, pro – and anti-inflammatory cytokines by postnatal MMSCs from various tissue sources during in vitro co-cultivation with immunoisolated pancreatic β-cells

Goncharov A.G., Shupletsova V.V., Todosenko N.M., Goncharova E.A., Litvinova L.S.


The article presents the results of evaluating growth factors, pro – and anti-inflammatory cytokine production by multipotent mesenchymal stem cell cultures under the conditions of co-cultivation with immuno-isolated beta-cells of the pancreas. β-cell transplantation is a minimally invasive therapeutic approach (compared to transplantation of entire pancreas), and it provides better metabolic control with respect to insulin administration. However, when transplanting β-cells, there is always a risk of immune rejection of the grafted cells. It is generally recognized that encapsulation is an effective means of immunological protection against the recipient’s immune system during transplantation. Regulation of the autoimmune response to transplanted cells is crucial for the treatment of type I diabetes mellitus. In recent years, along with replacement of islet cells, much attention has been paid to the use of multipotent mesenchymal stem cells with immunomodulatory and/or immunosuppressive properties, aimed for the correction of diabetes mellitus. Either in vitro and in vivo, they impact not only T-lymphocytes, but also B-lymphocytes, dendritic and NK-cells. Mesenchymal stem cells are able to inhibit proliferation of immune cells and reduce their secretion of inflammatory cytokines, acting as auxiliary cells to improve the survival of islets in the early post-transplant phase. Combined transplantation of multipotent mesenchymal stem cells and pancreatic β-cells is a promising approach to the treatment of type I diabetes mellitus. Deeper study of the mechanisms that cause their cytoprotective effect upon the transplant may be helpful for implementation of this therapeutic approach and improve its efficiency. In our study, a 1% solution of low-viscosity sodium alginate with addition of saline solution (0.9% sodium chloride) was used to create immuno-insulating scaffolds, and a 2.2% BaCl2 solution was added for polymerization. Decreased production of proinflammatory cytokines (TNFα, IL-12, IL-5) and growth factor (GM-CSF) was registered in co-cultures of β-cells with mesenchymal stem cells of bone marrow origin, and those obtained from subcutaneous adipose tissue. Anti-inflammatory activity was more pronounced in adipose stem cells and their immunomodulatory effects were shown via changes of their cytokine-producing activity. Hence, the multipotent mesenchymal stem cells obtained from adipose tissue and bone marrow have shown to exert cytoprotective effect upon pancreatic beta-cells by shifting the cytokine-producing activity towards an antiinflammatory profile.

Russian Journal of Immunology. 2021;24(4):477-482
pages 477-482 views

CD36 expression intensity on different subpopulations of circulating monocytes depending on the extent of subclinical atherosclerosis

Dolgushin I.I., Genkel V.V., Baturina I.L., Savochkina A.Y., Minasova A.A., Kuznetsova A.S., Shaposhnik I.I.


It is known that chronic activation of innate immunity and persistent low-intensity inflammation play a crucial role in the initiation and progression of atherosclerosis. It was found that atherogenic lipoproteins can act as inducers of the inflammatory response through ligand-receptor interaction with pattern-recognizing receptors of immunocompetent cells, such as CD36 (SR-B2) and Toll-like receptors. It is suggested that expression of CD36 on circulating monocytes may represent the burden of systemic atherosclerosis and, therefore, act as its diagnostic marker. The aim of the present study was to assess the intensity of CD36 expression on circulating monocytes of different subpopulations in patients without established cardiovascular disease (CVD) depending on the extent of subclinical atherosclerosis of peripheral arteries. One hundred patients without established atherosclerotic CVD, 49 (49.0%) men and 51 (51.0%) women, were included in the study. Monoclonal antibody conjugates were used to phenotype monocyte subpopulations. The expression of CD36 on CD14++CD16- monocytes (classical monocytes), CD14+CD16+ monocytes (intermediate monocytes), CD14+CD16++ monocytes (non-classical monocytes) was determined by the average fluorescence intensity. There was a statistically significant decrease in CD36 expression intensity on classical and non-classical monocytes with increasing number of vascular basins affected by atherosclerosis. A statistically significant decrease in CD36 expression intensity on classical and non-classical monocytes was found in the patients with two vascular beds lesions in comparison with patients with a single vascular bed lesion upon pairwise comparisons.

Russian Journal of Immunology. 2021;24(4):483-488
pages 483-488 views

Special features of interferonlambda contents in blood serum of the patients with HIV infection

Knysh S.V., Sklyar L.F., Markelova E.V., Kuznetsov A.S., Solovyeva N.P., Levenets M.A.


Studies in HIV infection remain an important issue for modern medicine, which, becomes controlled due to widespread usage of antiretroviral therapy. At the same time, however, it cannot be cured completely, and there is a number of “white spots” in understanding immunopathogenesis of disorders complicating this disease. The in-depth studies of interferon system, in particular from the lambda family, are desirable, because of their antiviral activity in HIV-infected patients. The aim of our study was to evaluate the content of interferons-lambda: IFNλ1 (IL-29) and IFNλ3 (IL-28B) in patients with HIV infection.
Blood serum of 120 patients with HIV infection (average age 49.7±6.2 years) who were treated in the outpatient setting at the Center for AIDS Prevention and Control of Regional Clinical Hospital No. 2 in Vladivostok was subjected to laboratory testing. HIV infection 4A was the main clinical diagnosis in all the patients, i.e., the stage of secondary diseases, remission phase on the background of antiretroviral therapy (ARVT). In 52 patients, chronic viral hepatitis C was found as a concomitant disease. The content of IFNλ1 (IL-29) and IFNλ3 (IL-28B) in venous blood serum was determined by ELISA technique using a “Multiscan” analyzer. The ELISA reagents were from R&D systems, catalog numbers DY5259; DY7246.
In the groups of patients with HIV infection, both with and without viral hepatitis C, the levels of IFNλ1 (IL-29) and IFNλ3 (IL-28B) were significantly reduced in comparison with control group. When comparing the IFN values between the groups, a more pronounced decrease in IFNλ1 (IL-29) was revealed among the patients with viral hepatitis C. When analyzing the level of IFNλ3 (IL-28B), an opposite pattern was observed, i.e., its values in the patients with HIV infection and viral hepatitis C were higher than in the group without hepatitis, but still did not reach appropriate values of the control group. Based on the data on IFNλ3 (IL-28B) antiviral effect upon HIV transmission via macrophages One may assume that induction and maintenance of higher type 3 interferon levels can favorably affect the course of HIV infection. The registered changes in IFNλ1 (IL-29) and IFNλ3 (IL-28B) levels in the patients with HIV and HCV suggest some viral effect upon innate immunity characterized by multidirectional changes, depending on presence or absence of hepatitis C virus. The studies of changes in innate immunity and role of type 3 interferons may extend our knowledge on the interaction between the human body and HIV, and will promote preventive measures and rehabilitation in the patients with HIV infection.

Russian Journal of Immunology. 2021;24(4):489-494
pages 489-494 views

Metabolic therapy of predicted complications in immunocompromised recipients before repeated corneal transplantation

Komakh Y.A., Borzenok S.A., Petrichuk S.V., Kuptsova D.G., Radigina T.V.


One of the topical problems of modern ophthalmotransplantology is the graft engraftment after repeated keratoplasty. During repeated corneal transplantation, the frequency of graft rejection increases significantly. The study included 121 patients aged 19 to 89 years with corneal graft failure, who were scheduled for repeated corneal transplantation. Immunophenotyping of major and small populations of peripheral blood lymphocytes was performed by flow cytometry (CytoFlex BC, USA). The intensity of energy metabolism in lymphocyte populations was determined by the activity of succinate dehydrogenase and NADH dehydrogenase by immunocytochemical method using flow cytometry. An increase in the content of B lymphocytes (p = 0.004) and a decrease in Th17 lymphocytes (p = 0.013) were revealed after the use of a course of metabolic therapy. Against the background of therapy, the activity of SDH in the T lymphocyte population significantly increases (p = 0.034). In addition, in the studied populations of lymphocytes in the recipient group, against the background of metabolic therapy, the normalization of SDH activity is observed: the number of recipients with low and high enzyme activity decreases. After a course of metabolic therapy, a significant decrease in NADHDH activity was revealed (p = 0.034). Indicators of lymphocyte populations and mitochondrial enzyme activity in recipients after a course of metabolic therapy indicated a more favorable prognosis for repeated corneal transplantation. Evaluation of the results of repeated keratoplasty a year after surgery showed that 59 recipients received transparent graft engraftment, and in 62 patients the graft became cloudy in the period from 1 to 8 months after surgery. In the group of patients with transparent graft engraftment, the percentage of recipients receiving metabolic therapy was significantly higher than in the group of recipients with graft opacity (41%±2.05% vs 21%±2.91%, p < 0.001). Conducting metabolic therapy before surgery reduces the number of realized unfavorable prognoses of the result of rekeratoplasty, and monitoring the activity of dehydrogenases and the content of lymphocyte populations allows us to evaluate the effectiveness of therapeutic and preventive measures in immunocompromised recipients.

Russian Journal of Immunology. 2021;24(4):495-500
pages 495-500 views

Evaluation of tissue factor expression on monocytes in the patients with sepsis

Lazanovich V.A., Markelova E.V., Shumatov V.B., Postnova B.E.


Sepsis is nearly always associated with some type of haemostatic disorder. The factors that play main causal role in pathogenesis of these processes are pro-inflammatory cytokines, vascular endothelium, platelets, leukocytes, and tissue factor (TF) expressed on these cells, which is always in an active state. Given a potential relationship between the blood clotting and pathophysiology of sepsis, TF may be considered a biomarker for early diagnosis, risk stratification, and prognosis of disease outcome in sepsis. Objective – to study quantitative content (CD14+CD142+) and the levels of TF expression on monocytes in the patients with sepsis, to analyze the dependence of these parameters on the severity of multiple organ dysfunction according to the SOFA scale, and disease outcomes.
67 patients with sepsis were examined. The severity of multiple organ dysfunction/failure was assessed by means of the SOFA score (Sepsis-related Organ Failure Assessments, Sequential Organ Failure Assessment). All the patients were divided in 2 groups based on the severity of their condition and extent of organ failure. Group 1 (n = 30) included the patients diagnosed with sepsis and severe organ dysfunction of < 6 points on the SOFA scale; Group 2 (n = 37) consisted of the patients with sepsis and organ dysfunction of > 6 points according to the SOFA scores. Blood sampling from patients was made within initial 48 hours after admission and diagnosis. Quantitative content (CD14+CD142+) and the level of expression of tissue factor on monocytes were investigated by flow cytometry. We have found that the content of (CD14+CD142+) cells was significantly higher in patients with sepsis than in healthy individuals (6.03±1.05% vs 0.24±0.02%, p = 0.001), being higher in more severe organ dysfunction (SOFA) vs less severe cases (SOFA) (6.50±0.98% versus 4.42±0.36%, p = 0.05). High level of TF expression on monocytes showed a direct correlation (r > 0.71; p = 0.05) with severity of organ dysfunction (SOFA), and it was associated (p = 0.004) with lethal outcome of the disorder. These results suggest that expression of tissue factor on monocytes can serve as a biomarker reflecting the degree of systemic inflammation in sepsis, thus being a criterion for predicting clinical severity and outcome of the disease in patients with sepsis.

Russian Journal of Immunology. 2021;24(4):501-506
pages 501-506 views

Сongenital immunity dysfunction in patients with postoperative cognitive impairment after coronary artery bypass grafting

Markelova E.V., Zenina A.A., Silaev A.A., Chagina E.A., Fedyanina L.N.


With regard of post-surgical cognitive disturbances, an active search for biological markers of these neurological complications is performed. We have studied the contents of NSE, IL-6, TGF-β1, MMP9 and TIMP1 in blood serum of these patients. The study included 110 patients after aortal-coronary bypass surgery using extracorporeal blood circulation. Splitting into separate groups was based on the test scores, according to Montreal Cognitive Assessment Scale prior to surgery and on day +7 after the intervention: (I) patients without complications (< 3 points); (II) patients with post-surgical cognitive impairment (> 3 points). The comparison group (III) included 35 healthy subjects. Evaluation of NSE, IL-6, TGF-β1, ММP9 and TIMP1 in blood serum was performed by means of ELISA technique (R&D Systems, USA). The data were expressed as pg/ml, or ng/ml. Blood sampling was made at 4 terms: before surgery, just after intervention, 24 h later, and on day 7 after the surgery.
The patients from group II showed higher NSE levels, except of 7 days after surgery when it became similar to other groups. Increased IL-6 levels were found in the patients from group II at all terms after surgery. Decreased concentration of TGF-β1 was found in the II group prior to operation, 24 h and 7 days after the surgery. However, just after surgery, this index was increased, and its values barely differed from results of groups I and III. Studies of MMP9 showed significant differences between groups I and II only on day +7 after. However, lower MMP9 content was detected in the patients from I and II groups before surgery compared to group III. TIMP1 values showed gradual increase over the observation period, but did not differ between groups I and II. In the patients from group II, an increased content of NSE and IL-6 was revealed, along with low TGF-β1 levels and decreased ММP9/TIMP1 ratio over early postsurgical period, thus suggesting possible role of innate immunity dysfunction in pathogenesis of postsurgical cognitive impairment.

Russian Journal of Immunology. 2021;24(4):507-512
pages 507-512 views

Allergic disorders in children living in different climatic and oecological areas of the Kaliningrad region

Markhaichuk A.Z., Gorbunova A.Y., Sidorova D.A., Razina A.S., Goncharova E.A.


The immune system responsible for genetic stability of internal environment, with its exceptional sensitivity, may provide biological indexes which reflect impact of various environmental (biotic and abiotic) factors, i.e., serve as an indicator system in the areas of environmental well-being and distress. A series of studies on the influence of climatic and environmental factors on immune reactivity states demonstrated that the immune system is also sensitive to both natural and industrial factors (chemical and physical). Apparently, this is due to formation of a population-based immunological reactivity adapted for specific environmental conditions. However, the distribution patterns of immunogram variability by geographical zones are still unclear. The article analyzes prevalence and structure of allergic disorders in children of 1-3 and 4-7 y.o. (early and first childhood)living in different climatic and ecological areas of Kaliningrad region (coastal and continental zones, “clean” and “dirty” cities, different for anthropogenic burden and environmental situation). The following cities were involved into the study: Svetlogorsk, Svetly, Kaliningrad, Sovetsk, Gusev and Neman. There were 3,321 children examined. Clinical and demographic data were taken from the following sources: “History of the child’s development” (Form No. 112/y), “Outpatient medical record card” (Form No. 025/y) and “Diagnostic card of immunological deficiency in children”, developed at the Institute of Immunology (Federal Medical&Biological Agency of Russia) which contained the patient’s data, seasonality of increased morbidity, vaccination history, acute infections). Disorders and reactions attributable to allergic syndrome were divided into three groups: skin diseases, respiratory system diseases, adverse response to various antigens. The revealed differences demonstrate high sensitivity of immune system to climatic and environmental factors acting at the sub-threshold level. We believe that the child’s immune system responds even to minor environmental factors, which, acting in combined manner, cause its functional shifts. In turn, these changes manifest at the level of immunobiological reactivity and, accordingly, influence clinical course and symptoms of the allergic disorders.

Russian Journal of Immunology. 2021;24(4):513-518
pages 513-518 views

Local changes in the type 3 interferons in women with human papillomavirus infection before and after treatment with Inosine pranobex

Nevezhkina T.A., Kostyushko A.V., Krasnikov V.E., Matyushkina L.S., Bovdui M.A.


 Papillomavirus infection remains one of the main causes of pathological conditions of the female reproductive tract. Innate immunity is one of the first protective mechanisms against this infection, with interferon system being one of its elements. Due to ability of HPV for immune evasion, and lack of uniform clinical recommendations and protocols for management and treatment of women with papillomavirus infection, further studies on probable usage of immunomodulatory drugs are an urgent issue for both fundamental and clinical medicine. Currently, a lot of antiviral and immunomodulatory drugs is used in the treatment of virusassociated diseases of urogenital tract associated with a Th1/Th2 type imbalance. However, the drugs with Inosine pranobex as active substance seem to be the most effective and safe drugs for PVI. The aim of our study was to determine type 3 interferons in the cervical mucus of the women before and after Inosine pranobex therapy.
We have examined 42 patients with papillomavirus infection treated with drugs with the active substance Inosine pranobex. The average age of women was 31±4.1 years. The levels of IL-29 (IFN
λ1) and IL-28 (IFNλ3)
in cervical mucosa were determined using specific reagents from R&D Diagnostics Inc. (USA). The levels of IL-29 (IFN
λ1) were increased in all the groups compared to controls. After treatment, these indexes were
significantly higher, compared with the group before treatment. IL-28 (IFN
λ3) had opposite results to IL-29 (IFNλ1). Thus, in the groups of samples taken before and after therapy, the indexes increased in comparison with the group before treatment, demonstrating the course of recovery towards reference values. The dynamics of studied indexes may be associated with early evaluation period, due to longer duration of immunological changes leading to induction of promoter gene expression, as well as due to insufficient stimulation of these genes. Usage of Inosine pranobex was associated with significantly increased levels of IL-29 (IFNλ1) as soon as a month after therapy. Taking into account genetic homology of type 3 interferons, we may assume that the use of Inosine pranobex drugs in the patients with papillomavirus infection is substantiated, and it may positively affect prognosis of the disease, due to induction of the non-specific immune response. 

Russian Journal of Immunology. 2021;24(4):519-524
pages 519-524 views

Serum macrophage colony-stimulating factor levels in patients with essential hypertension after vaccination against SARS-CoV-2

Radaeva O.A., Simbirtsev A.S., Kostina Y.A., Iskandyarova M.S., Mashnina S.V., Negodnova E.V., Besheynov D.D.


The formation of immunity in the population to various variants of the COVID-19 pathogen is one of the most important problems for the world community. The aim of the study was to compare the dynamics of M-CSF and VEGF-A, IL-34 in the blood serum of patients with essential hypertension (EH) stage II, depending on the type of immunity formed (post-infectious, post-vaccination, “hybrid”) to analyze changes of M-CSF-mediated mechanisms of hypertension development. During the work, 2 groups of patients were formed: group 1-patients with stage II EH and SARS CoV-2 infection without pneumonia in the anamnesis, vaccination 6 months after laboratory recovery, group 2 – patients with stage II EH without COVID-19 in the anamnesis, vaccination during the follow-up period. Determination of M-CSF, IL-34, VEGF-A, IgG level to SARS-CoV-2 was determined using an enzyme-linked immunosorbent assay. The formation of post-infectious immunity in patients with stage II EH, despite the mild course of COVID-19, is accompanied by a long-term (up to 6 months) pathophysiologically significant increase in the serum level of M-CSF (p < 0.001) with a decrease in IL-34 (p < 0.001). Analysis of the dynamics of changes in M-CSF, IL-34, VEGF-A in the postvaccination period in the blood serum of patients with stage II EH with COVID-19 in the anamnesis (“hybrid” immunity), determined the absence (p < 0.05) of changes in the levels of M-CSF, VEGF-A after the first component of “SPUTNIK V” against the background of an increase of the level of IgG to SARS-CoV-2. 21 days after the second component of the vaccine, an increase of M-CSF was detected when compared with both pre-vaccination indicators and data 21 days after the introduction of the first component of the vaccine (p < 0.001). Comparing the dynamics of the of M-CSF, IL-34 and VEGF-A in patients with stage II EH without COVID-19 in the post-vaccination period with the data on the formation of “hybrid” immunity, an increase in M-CSF was recorded 21 days after the introduction of the first and second components against the background of a decrease in IL-34, but with the restoration of pre-vaccination concentrations in 100% of patients by day 180 with comparable immunogenicity after 180 days. In patients with EH II, the pathogenetic “summation” of the pre-infectious imbalance of cytokine regulation and postcovid changes is important, which in a number of patients may be the reason for the prolongation of the stabilization of the balance of the M-CSF-IL-34-VEGF-A system in the post-vaccination period during the formation of “hybrid” immunity.

Russian Journal of Immunology. 2021;24(4):531-538
pages 531-538 views

Particular features of humoral immunity in patients with 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 neurological disorders in the world. Meanwhile, usage of neuroimaging methods does not allow precise assessment of its severity and clinical prognosis. This predetermines for searching new techniques of differential diagnosis of the TBI severity and predicting the risk of consequences. Currently, many authors have shown an association between disorders of the immune system manifesting as a decrease in general immune status, and development of cellular/humoral neurosensitization with progredient outcome of the brain injury. At the same time, the role of humoral mechanisms in pathogenesis of TBI, in particular, brain commotion, is less studied in comparison with cell-mediated mechanisms, thus suggesting a need to studying the role of activation or, vice versa, anergy of the humoral immunity in mild traumatic brain injury. The aim of this work was to study characteristics of B-lymphocyte subpopulations in peripheral blood of the patients with brain concussion (n = 22). Peripheral blood samples obtained from 52 apparently healthy volunteers served as controls. The diagnosis was made in accordance with established international criteria. In this case, the exclusion criterion were as follows: severe concomitant organ damage or somatic pathologies, as well as presence of intoxication. General examination included the collection of complaints, medical history, assessment of the somatic and neurological status. B-lymphocytes were determined using multicolor flow cytometry based on two approaches: IgD/CD38 expression (“Bm1-Bm5” classification), and IgD/CD27. We have found that the relative number of naïve Bm1 (IgD+CD38-) was significantly higher in patients with brain concussion than in conventionally healthy individuals (p < 0.001). The relative content of activated naive Bm2-cells (IgD+CD38+) was significantly lower in the group of TBI patients than in controls (p < 0.05). The number of naive cells (IgD+CD27-) was also significantly reduced in the brain concussion group compared to the control group. The data obtained indicate a possible significant role of B-cell immune response in pathogenesis of clinical course following the brain concussion, thus enabling assessment of possible features of humoral immune response.

Russian Journal of Immunology. 2021;24(4):525-530
pages 525-530 views

Dynamics of cytokine production during immunization with polio vaccine with DTP in vivo

Samoylikov R.V., Kuznetsova V.S., Namiot E.D., Kraskevich D.A., Leonova A.Y., Grechenko V.V.


Immunization with whole-cell adsorbed diphtheria-tetanus-pertussis vaccine (DTP) can cause various undesirable effects. The most common complications are febrile seizures, neuromyalgic syndrome and, in more severe cases, various encephalopathies. The listed complications are quite dangerous, especially in childhood, when primary DTP immunization is carried out. Many studies indicate that the development of these pathological processes is often associated with the action of various cytokines produced in response to vaccination. There are specific pro- and anti-inflammatory cytokines, the high levels of which are associated with the development of neurological complications after DTP vaccination. For example, IL-6 and IL-1 are often associated with the development of febrile seizures and encephalopathies. On the other hand, there are clinical data indicating a decrease in the incidence of complications after concomitant administration of vaccines. Thus, it is of particular interest to study the cytokine profile after the combined administration of DTP with another vaccine, which in some cases leads to a decrease in the number of complications and better tolerance of the vaccine. The vaccine against polio infection is currently one of the safest, but its effect on the level of cytokines is extremely poorly understood. Moreover, due to the fact that these drugs have been used for a long time and the interest in them is not as high as before, the number of new experimental works specifically on the cytokine profiles of many vaccines is limited. Basically, all existing work is aimed at studying various pathological processes associated with the introduction of a vaccine preparation. This leads to the fact that the mechanism of the formation of the immune response remains not fully understood. The aim of this work was to study the effect of combined vaccine administration on the cytokine profile. Results were obtained for the following cytokines: IL-2, RANTES, Eotaxin, MIP-1β, IL-12p40, IL-4, IL-6, IL-1α, and G-CSF determined in murine serum samples after combined administration of DTP and polio vaccine to the experimental animals. The cytokine profile was determined using Bio-Rad MAGPIX fluorescence reader. The study revealed and described the patterns of changes in the cytokine profile, both with the administration of the poliomyelitis vaccine alone, or in combination with the DTP vaccine. The results obtained in this work may be further used for more detailed studies on the mechanism of the immune response formation upon combined administration of vaccines and further improvement of existing drugs.

Russian Journal of Immunology. 2021;24(4):539-546
pages 539-546 views

Indexes of innate and adaptive immunity in the patients with SARS-CoV-2 infection

Sitdikova T.S., Kabieva A.A., Prosekova E.V.


The main pathogenetic mechanisms of the SARS-CoV-2 infection include imbalance of immune response and impaired cytokine regulation involving insufficient interferon synthesis at the onset of the disease, and subsequent hyperproduction of proinflammatory cytokines resulting in marked inflammation and damage of pulmonary parenchyma. Our objective was to perform monitoring of cytokine content, determination of antibodies, immune cells, and inflammatory biomarkers in the patients who had coronavirus infection caused by COVID-19, during the disease and over the convalescence period. The study included sixty patients at the age of 18 y.o. and older with severe and moderate course of disease caused by COVID-19. The diagnosis was verified in accordance with provisional instructional guidelines of the Ministry of Healthcare of the Russian Federation “Prevention, diagnosis and treatment of novel coronavirus infection (COVID-19)” version 11 (17.05.2021). The study involved analysis of medical documents, evaluation of differential white blood cell count, T cell subpopulations, C-reactive ptrotein (CRP) levels, interleukin-6 (IL-6), interferon gamma (IFNγ), tumor necrosis factor-alpha (TNFα), as well as IgM and IgG antibodies against SARS-CoV-2.
Statistical processing of data was performed by Statistica 13 program with critical significance level p < 0.05, correlations were analyzed using Spearman rank correlation coefficient, multidimensional correlation analysis with creation of pleiads, according to V.P. Terentyev’s method (1959), and Shapiro–Wilk testing for normality of data distributions. The sample size made it possible to evaluate the results at a significance of 95-99%. These studies have yielded the results concerning specific changes of the inflammatory biomarkers at different stages of disease, persistent changes in quantitative and qualitative characteristics of immune cells and cytokine levels, correlations between immunological indicators and severity of clinical course, and degree of damage to pulmonary parenchyma. During the period of significant clinical presentations, the patients with severe course of disease exhibited leukopenia with low proportion of lymphocytes, and maintenance of CRP and ESR at high levels for longer terms, including early recovery. Levels and changes in amounts of IgG and IgM antibodies to SАRS-CoV-2 varied in accordance with clinical severity and duration of convalescence period. During the recovery period, an imbalance of regulatory T cell subpopulations and low levels of IFNγ were observed. The stable impairment of structural and functional characteristics of immune cells and aberrant production of cytokines during the disease caused by SARS-CoV-2 may serve as a pre-requisite for monitoring immunological indices in search for personalized immunotropic therapy.

Russian Journal of Immunology. 2021;24(4):547-554
pages 547-554 views

Extended haplotypes based on rare single nucleotide polymorphisms of TNFA and HLA DRB1 associated with rheumatoid arthritis

Stashkevich D.S., Khromova E.B., Devald I.V., Khodus E.A., Burmistrova A.L.


Rheumatoid arthritis (RA) is a multifactorial disease, with genetic component based on intergenic interactions leading to the formation of gene networks. The current trend in RA immunogenetic studies is to assess the gene-to-gene interactions. Among possible genetic factors contributing to RA development, the genes of main histocompatibility complex (HLA class II) play a fundamental role. TNFA gene is among possible candidate genes providing susceptibility to this disorder and contributing to its immune pathogenesis. The special location of this gene suggests arrangement of extended TNFA – HLA haplotypes. This work analyzed the distribution features of two-locus SNP haplotypes (TNFA and HLA DRB1) for their association with rheumatoid arthritis in Russians. The following methods were used: DNA isolation, PCR-based genotyping, RFLP analysis with electrophoretic detection. Calculation of two-locus haplotypes frequencies and linkage disequilibrium (D’; χ2; p) was carried out using the EM algorithm in the Arlequin ver 3.5 program. Comparison of paired samples was carried out using standard immunogenetic criteria. The significance level was < 0.05. Analysis of the data showed that the two-locus haplotypes -1031T/C and -863C/A TNFA were not associated with predisposal for rheumatoid arthritis in Russian population sample. The haplotypes associated with predisposition for RA were TNFA -863*a – HLA DRB1*03, TNFA -1031*t – HLA DRB1*04, TNFA -1031*t – HLA DRB1*04. Meanwhile, TNFA -1031*t – HLA DRB1*15; TNFA -1031*t -HLA DRB1*11 proved to be protective haplotypes. Our study showed that, in addition to individual HLA II alleles, the predisposal or resistance to rheumatoid arthritis may be promoted by haplotypes of rare SNPs at positions -1031, -863 C/A of TNFA gene, and HLA DRB1.

Russian Journal of Immunology. 2021;24(4):555-562
pages 555-562 views

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Russian Journal of Immunology. 2021;24(4):563-565
pages 563-565 views

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