Search

Women of reproductive age with type 1 diabetes mellitus (DM) and chronic kidney disease stage 5 after successful combined pancreas-kidney transplantation (CPKT) can experience spontaneous pregnancies with a favorable outcome. However, those pregnancies are associated with a high risk of complications: arterial hypertension, preeclampsia, premature birth, progression of diabetic retinopathy. During pregnancy, both gestational diabetes and spontaneous hypoglycemia can develop. This article presents a description of the clinical case of a 42-year-old patient with DM type 1, in whom pregnancy occurred 2 years after successful CPKT. Blood pressure was normal, the fundus condition was stable after previous treatment. The patient received tacrolimus and minimal dose of corticosteroids, at 13 weeks acetylsalicylic acid was prescribed to prevent preeclampsia. At 30 weeks nocturnal episodes of hypoglycemia appeared that were treated by additional intake of carbohydrates with an average glycemic index in combination with animal fats and proteins. At 36 gestational weeks caesarean section was performed due to premature rupture of membranes. A healthy girl was born with weight of 2140 g, height of 48 cm, Apgar score 7/8 points. The mother’s function of the kidney and pancreas grafts remained normal. Preconceptional counseling and multidisciplinary pregnancy management are important for patients after CPKT.

Solid organ transplantation is considered the most effective treatment for endstage heart, lung, pancreatic, liver, and kidney diseases. The increasing number of transplants performed, and long-term survival of recipients have contributed to an increase in the diagnostic rate of non-transplant-related diseases.Heart transplant patients are at increased risk of complications when undergoing elective or emergency surgery. We report a case of hip replacement in a young man after orthotopic heart transplantation.

The search for domestic publications on this publication was conducted in the database on the RSCI website, and foreign ones in the PubMed and Google Scholar databases in the period 2022-2023. Their analysis showed that actively studied approaches to the immunocorrection of sepsis are aimed at changing the content or activity of cytokines, growth factors, the use of immune checkpoint inhibitors, as well as myeloid suppressor cells. When modulating the action of cytokines, a variety of approaches are used, such as changing the affinity of cytokines to their receptors, extending the half-life of cytokines and «fine-tuning» the action of cytokines. For the safe and effective use of bioregulators for immunocorrection in sepsis, additional multicenter studies of their clinical effectiveness are needed, including taking into account the stratification of patients into individual endotypes and the mechanisms of action of bioregulators.

justification. Degenerative retinal diseases associated with retinal pigment epithelium damage are untreated and lead to irreversible vision loss. The most promising approach nowadays is considered to be the transplantation of retinal pigment epithelium differentiated from pluripotent stem cells (PSC-RPE). When testing biomedical cellular products, special requirements are placed on the animal model, which should simulate pathological changes, such as in humans, and have sufficient immunological tolerance to xenogenic human cells, enabling them to function fully. For this purpose, lines of immuno-modified or immunodeficiency animals are used, usually small rodents (rats and mice), but the small size and structure of their eyes do not allow manipulation in vitreoretinal interventions in humans. An alternative method of preventing xenotransplantation rejection in large models is pharmacological immunosuppression, under which transplanted PSC-RPE may have biological effects. However, targeted studies of the effectiveness of PSC-RPE transplantation with use of immunosuppressive therapy have not been conducted in our country, and the data of a few foreign works devoted to this problem are contraversial.Purpose. Study of immunological reactivity in transplantation of IPSC-RPE under combined immunosuppressive therapy in rabbit experiment.Materials and methods. The study was performed on 27 male rabbits of New Zealand albino breed, of which 24 animals underwent subretinal transplantation of induced pluripotent stem cells of retinal pigment epithelium: in the I group (12 eyes) intervention was performed in the healthy eye; in group II (12 eyes) — in the area of pre-modeled atrophy of retinal pigment epithelium. Recipients were given combined immunosuppressive therapy. Control Group — 3 intact rabbits (6 eyes). The observation period was 14, 28 and 60 days. Post-transplant evaluation was carried out using standard and specialized ophthalmological examination methods. The determination of cytokines of the immune response IL-2, IL-6, immunosuppressive factors TGF-β1, TGF-β2, TSP-1 in the serum of the blood and the vitreous body was performed by solid-phase immunosurgical enzyme analysis.Results. Comprehensive analysis of biomicroscopy, ophthalmoscopy, optical coherent tomography, immunological studies revealed no signs of active inflammation; no local and systemic increase in the concentration of acute phase IL-6, a drop in serum IL-2 levels indicated direct effects of immunosuppressive drug combinations used in this study.Conclusion. The use of combined immunosuppressive therapy prevented rejection of xenogenic material in rabbits and obtained evidence of safety of subretinal transplantation of IPSC-RPE suspension both in the healthy eye, and pre-induced atrophy of pigmentary epithelium.

We report a case of cytomegalovirus (CMV) colitis. The patient (a woman with a provisional diagnosis of Crohn disease) presented with severe abdominal pain, diarrhea, and weight loss. Despite difficulties in differential diagnosis, we were able to make the correct diagnosis based on findings of the histological examination of the biopsy specimens obtained during colonoscopy: intranuclear inclusions characteristic of CMV and specific CMV-associated changes in the intestinal mucosa. This case highlights the importance of histopathological examination in differential diagnosis of inflammatory diseases of the gastrointestinal tract.

Glomerulonephritis (GN) is a group of immuno-inflammatory kidney diseases with predominant glomerular lesions that are difficult to treat. The greatest problems are caused by the treatment of GN with nephrotic syndrome, which often has a recurrent course. The aim of the research was to study the effectiveness of recombinant interleukin-2 (rIL-2) therapy in the GN patients with nephrotic syndrome. 62 patients with a nephrotic form of primary GN with frequent relapses admitted to the Nephrology Department have been recruited into the study. The age of patients was from 18 to 65 years. The patients underwent standard examinations, as well as immunological studies, before administration of the anti-relapse treatment, and 12 months after the treatment was started. Immunological testing included immunophenotyping of lymphocytes with counting of T and B lymphocytes, immunoregulatory and activated subpopulations of T lymphocytes, determination of urinary immunoglobulins (IgM, IgG, IgA) by immunoturbidimetric assays, proinflammatory cytokines – IL-1β, IL-8, IL-17A and anti-inflammatory cytokine IL-10 by ELISA tests. As a result of studies, the examined patients showed an increased contents of T helper cells, activated T lymphocytes (CD8+HLA-DR+CD45+, CD3+CD8brightCD38+) along with decreased numbers of Treg cells and an increased contents of proinflammatory cytokines IL-1β, IL-8, IL-17A and immunoglobulins of all three classes in urinary samples.The cohort of patients with GN selected for the study was divided in two groups (the main group and the comparison group). In addition to nephroprotective and steroid therapy, the treatment regimen of patients included rIL-2 in the main group, or cyclophosphamide in the comparison group. Regardless of the method used, the levels of protein, IgG and IL-17A in the urine proved to be decreased relative to the initial values; the contents of B cells and HLA-DR+ cytotoxic T lymphocytes in peripheral blood were found to be decreased. The revealed changes were more pronounced in the main group of patients. By 12 months after starting the treatment, the mentioned indexes began to differ significantly in the main group from those in the comparison group. Serum creatinine levels, numbers of T helper cells and Treg cells, IL-1β levels in urine did not undergo significant changes in the comparison group, whereas a decrease in serum creatinine and urinary IL-1β was registered in the main group of patients, along with decreased number of T helpers and increased numbers of Treg cells. In the main group of patients treated with rIL-2, the average number of relapses per year decreased by 4 times, showing only a 1.2-fold decrease in the comparison group. Hence, the low-dose therapy with rIL-2 may be considered an effective and safe alternative to conventional immunosuppressive therapy and a new option of the targeted treatment of glomerulonephritis with frequent recurrence of nephrotic syndrome.

Objective. To study significance of herpesviruses in the development of infectious complications in patients after heart transplantation based on the detection of markers of herpesvirus infections. Materials and Methods. The paper presents the results of a comprehensive examination for markers (HVI) of patients who underwent orthotopic heart transplantation at the V.I. Shumakov National Medical Center of Transplantology and Artificial Organs (Moscow). A total of 86 patients were observed. To establish the etiological diagnosis of infectious complications, all the blood serum and blood cell samples were analyzed for markers of herpesvirus infections. The titers of IgM and IgG antibodies to herpesviruses (HSV1, HSV-2, EBV, CMV and HCV-6) in blood serum were determined using enzyme-linked immunoassay. Indirect immunofluorescence was used to detect herpesviruses and their antigens in peripheral blood leukocytes. Early CMV and HCV-6 antigens as well as reproduction of HSV and EBV were detected by a rapid cultural method. Results. There was a wide prevalence of herpesviruses in the studied groups. It was shown that in all groups of patients with reduced immunity, herpesviruses always manifested themselves as mixed infections. Conclusions. The study gives grounds to carry out laboratory diagnostics for all patients in order to differentiate the types of herpes viruses and the degree of their activity in order to identify activation and relief of infectious processes caused by herpes viral infections.

Rapidly rising prevalence of ulcerative colitis in developed countries among young population compels the medical community to pay attention not only to the problems of early diagnosis and therapy of this disease, but also to preventing the development of complications, that may lead to disability. This article reviews a clinical case of the development of surgical complications in a patient with a long-term active course of ulcerative colitis, who has been also suffering from autoimmune hepatitis and primary sclerosing cholangitis for 20 years. The prolonged active course of the disease and total damage to the colon, association with primary sclerosing cholangitis, as well as the patient’s low adherence to therapy were risk factors for the development of adenocarcinoma of the ascending colon, which required radical surgical treatment. The formation of adhesive disease and multiple abdominal abscesses can be noted as long-term complications, which led to the repeated use of invasive methods of treatment. Over the next few months, the patient experienced 2 more episodes of local purulent complications that required surgical treatment due to the ineffectiveness of antibiotic therapy. All episodes of purulent complications were accompanied by progressive leukopenia due to prolonged use of immunosuppressive drugs. In our opinion, in patients with ulcerative colitis who take cytostatic agents for a long time, special attention should be paid to monitoring and correcting leukopenia, as well as preventing the development of purulent complications.

In the article various ophthalmic manifestations of hemoblastoses will be discussed. Detailed descriptions of the most common variants of damage to the organ of vision in the oncohematological process are presented. Here we also present the clinical symptoms and development mechanisms associated with both direct leukocyte infiltration of various structures of the eye, occurring against the background of the underlying disease, and concomitant conditions, such as violation of the hemostasis system, anemia and thrombocytopenia resulting from the progression of blood cancer. It is also considered the cases of ophthalmic manifestations of hemoblastoses developing against the background of an immunity decrease associated oncohematological disorder, or as a result of the toxic effect of chemotherapy drugs, radiotherapy and bone marrow transplantation, as well as targeted therapy.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population that primarily suppress T lymphocytes in healthy pregnancies and pathologies. MDSCs are one of the key regulators of immune responses. Finding ways to control them is important for the treatment of cancer, autoimmune diseases, miscarriage, and post-transplant complications. The mechanisms of immune suppression by MDSC are: expression of CD73, ADAM17, PD -L1, production of Arg 1, iNOS, IDO, IL -10 and TGF-b1.Pregnancy-specific b1-glycoprotein (PSG) has modulatory effects on dendritic cells and macrophages that mediate the shift of T cell phenotypes toward Th2 and Treg. We have previously shown that native PSG suppresses Th17 differentiation and cytokine production, stimulates the production of IDO by monocytes and the differentiation of Tregs.Considering the immunomodulatory properties of PSG and the key role of MDSCs in pathologies, the aim of our work was to investigate the effect of native and recombinant PSG on the differentiation of MDSCs in vitro.MDSCs were differentiated from CD11b+ peripheral blood cells. Cells were cultured for 7 days and received stepwise GM-CSF, IL-1b, and LPS. Native (n) (1; 10 and 100 mg/mL) and recombinant (r) (1 and 10 mg/mL) PSG were introduced into the cultures three days before the end of incubation. Flow cytometry was used to determine the percentage of MDSC among the cells in culture and the percentage of M-, PMN-, and e-MDSC among the total number of MDSCs.It was found that rPSG (1 mg/mL) increased the percentage of MDSCs in culture. Both nPSG (1 and 10 mg/mL) and rPSG (10 mg/mL) increased the proportion of M-MDSC, whereas rPSG (10 mg/mL) decreased the number of PMN-MDSC.Thus, the cytokine background in CD11b+ cell cultures favored the differentiation of predominantly M-MDSC, similar to the tumor microenvironment, whereas native and recombinant PSG enhanced this effect. Thus, nPSG and rPSG are able to modulate the differentiation of MDSCs by increasing their number, mainly due to the monocytic subpopulation. This fact opens perspectives for new research on targeted manipulation of MDSCs.

Background. The purpose of the work is to study uterine morphogenesis and dynamics of the cytokine profile of the blood plasma of the reproductive period rats at correcting of methotrexate-induced immunosuppression with imunofan. Materials and methods. The study was carried out on 60 white mongrel mature female rats weighing 210-250 g. After synchronizing the estrous cycles, the animals were divided into 2 groups. Immunosuppression was modeled by administration of methotrexate to laboratory animals at a dosage of 10 mg/m2 of body area at the beginning of diestrus, followed by correction by intramuscular injection of the immunomodulatory agent imunofan at a dosage of 50 μg according to the scheme. Rats were taken out of the experiment into the proestrus phase (PE) of the 1st, 3rd, 5th, 7th and 9th estrous cycles, the absolute and relative mass of the uterus, the linear characteristics of its body and horns, and the volume of the organ were measured. Micromorphometric parameters were determined at the lightoptical level. To establish the characteristics of the state of the immune system, the content of mediators of intercellular interaction IL-1β, IL-2, IL-6 and TNFa in the blood plasma of animals was determined. Results. It was found out that the studied influence has a pronounced effect on the morphometric parameters of the uterus of white mongrel female rats of young reproductive age, and is also accompanied by statistically significant changes in the cytokine profile of animals. Conclusions. The results obtained indicate a favorable effect of imunofan on the dynamics of morphometric parameters of the uterus of mature animals as a corrector of acute immunosuppression.

Differential diagnosis of inflammatory myopathies with hereditary muscular dystrophies accompanied by a secondary inflammatory process is a time‑consuming clinical and pathomorphological task. In particular, false diagnosis of polymyositis in patients with dysferlinopathy reaches 25 % of cases.A 40‑year‑old female patient with a limb‑girdle phenotype of dysferlinopathy, initially diagnosed as polymyositis, is presented. The reasons that led to the erroneous diagnosis were: sporadic case; subacute onset; proximal muscle weakness; myalgia, which stopped on the glucocorticosteroid therapy; high levels of creatine phosphokinase (up to 17 times); the presence of lymphocytic‑macrophage infiltrate in the muscle biopsy and the absence of magnetic resonance imaging data in primary examination of the patient.The refractoriness of clinical and laboratory signs to complex immunosuppressive therapy was the reason for revising the muscle biopsy with typing of the inflammatory infiltrate. The predominantly unexpressed perivascular infiltrate was characterized by the predominance of macrophages and, to a lesser extent, CD4+, which indicated the secondary nature of the inflammation in the muscle observed in some hereditary muscular dystrophies. When conducting an immunohistochemical reaction, the absence of the dysferlin protein in the sarcoplasmic membrane was revealed.Whole‑exome sequencing (NGS) revealed a mutation in exon 39 of the DYSF gene (p.Gln1428Ter) in the heterozygous state, which leads to the appearance of a stop codon and premature termination of protein translation. MLPA method registered 3 copies of exons 18, 19, 20, 22, 24 of the DYSF gene.Thus, this clinical example reflects the main methodological errors and possible effects of immunosuppressive therapy in patients with dysferlinopathy.

The aim of the study is to evaluate the effect of R. uniflorum dry extract on morphofunctional state of mice thymus and spleen at cyclophosphamide immunosuppression.Materials and methods. The experiments were carried out on F1 (CBAxC57Bl/6) mice 18–20 g of weight. Immune deficiency was simulated by a single intraperitoneal introduction of cyclophosphamide in the dose 250 mg/kg. R. uniflorum dry extract in the dose 100 mg/kg was administered per os for 14 days. The thymus and spleen were fixed for histological studies on day 16. The thymus total area, the cortex and medulla area, the connective tissue capsule thickness, the spleen white and red pulp area were used to measure on micropreparations stained with hematoxylineosin and azure-eosin. The cell density and the cellular composition were calculated in the thymus cortical substance.Results. The R. uniflorum extract increased the thymus total area and the corticomedullary index by 37 and 26 % (p ≤ 0.05), respectively. The cells density increased in the cortical substance, it decreased in the medulla, as a result “layer inversion” is not observed in any animal of the experimental group. The number of proliferating lymphocytes, blasts and large lymphocytes increased; the number of destructive cells and macrophages decreased in the cortical substance. The spleen white pulp relative volume was 39 % higher than in the control.Conclusions. The R. uniflorum dry extract had an immunocorrective effect on the thymus and spleen morphofunctional state at cyclophosphamid immunosuppression.

Cytomegalovirus plays an essential role in human pathology. Primary infection usually occurs in childhood and subsequently, a lifelong latency is formed which the virus replicates by evading the immune response. In recent years, more and more researchers have concluded that cytomegalovirus reactivation may occur in critically ill patients. Despite the available evidence, data on reactivation in this group of patients are limited by the relatively small sample size, the variety of patient groups studied, the differences in study methodology, and the variability in reported results, which excludes the possibility of summarizing the results.This study aimed to determine the frequency of reactivation of cytomegalovirus infection in critically ill patients and to identify its main clinical features.Materials and methods. The study included 118 critically ill patients with severe bacterial and viral-bacterial infections accompanied by multiple organ dysfunction. Cytomegalovirus reactivation was determined by the detection of DNA in combination with the presence of IgG.Results. Reactivation was detected in 36.4% of cases. Frequency and terms of reactivation in blood and sputum as well as trends of viral load changes in dynamics were shown. The main clinical features of reactivation in different pathologies (sepsis of bacterial etiology, COVID-19, non-septic critical patients) were noted. HCMV DNA was more frequently detected in the blood of septic patients (44.8%) compared with COVID-19 (13.0%, p

The present study is aimed at determining the frequency and the characteristic features of reactivation of latent cytomegalovirus infection in patients with severe respiratory infections depending on the etiology of the pathogen. The study included 72 patients with severe bacterial and viral respiratory tract lesions. Cytomegalovirus (CMV) reactivation was determined by the detection of DNA in sputum together with the presence of IgG in blood plasma. The study found differences in the frequency of CMV reactivation in sputum of bacterial, bacterial-viral, and viral pneumonia (36.1%, 50.0%, and 20.0%, respectively). These results indicate that nosocomial bacterial flora may be a risk factor for CMV reactivation. Statistically significant differences were also found in the period of CMV reactivation depending on the etiology of the respiratory tract lesion. In the COVID-19 patients CMV was found in their sputum on days 1-7 (Me 3.0 days), in the bacterial-viral group – on days 1-20 (Me 10.0 days), and in the bacterial pneumonia group – on days 1-52 (Me – 20.0 days). Characteristic features in the dynamics of CMV viral load in the sputum of patients with different etiology of respiratory infections are described. The results indicate a different mechanism of CMV reactivation in case of COVID-19.

One of the greatest medical advances of the last century has been the introduction of organ transplantation. However, despite the considerable potential of transplantation as often the only therapy for severe diseases, the toxicity of immunosuppressive drugs supporting the transplant remains a serious problem for its further development. Modification of immune response in order to form tolerance to the transplanted organ can play an important role on the way to minimize immunosuppression. Successful cases of withdrawal of immunosuppressive drugs for medical reasons in kidney and liver transplantation recorded in the literature, as well as the results obtained in the process of modeling such a situation in the experiment, prove that achieving tolerance in organ transplantation is fundamentally possible.The aim of this review is to investigate the ways of immunologic suppression and fundamental mechanisms of immunologic tolerance in the field of transplantation and to review the latest clinical achievements in this respect.The review describes various approaches to the induction of central tolerance in solid organ transplantation implemented in the framework of the original clinical protocols. Special attention is given to a new direction in transplantation medicine – cell technologies providing tolerogenic effect by means of peripheral mechanisms activation, in particular due to activation of suppressor function of regulatory T cells.We draw the attention to the advantages and disadvantages of these two trends. Which of them is preferable? In which direction will scientific thought be developed for realization of the long-term goal of transplantologists: to avoid allograft rejection without affecting the physiological homeostasis of the body? Possible answers to these questions are discussed in this review.

The purpose is improving the prediction of the immune status dynamics in children with HIV infection, taking into account independent predictors.Materials and methods. Clinical, immunological, molecular genetic examination of 91 pairs «HIV-infected mother – child with HIV infection» was carried out. All children did not receive antiretroviral therapy. The age of children at the time of immunosuppression development was determined. The criterion for immunosuppression at the age of less than 1 year was a decrease in the number of CD4 lymphocytes to 30–35% (1,0–1,5 × 109 / l), at the age of 1–5 years – to 25–30% (0,75–0,999 × 109 / l), over the age of 5 years – up to 20–25% (0,35–0,499 × 109 / l). To determine the factors affecting the rate of development of immunosuppression, we used mathematical models for analyzing the time to event (survival) and proportional Cox intensities.Results. All children aged 9–54 months (median 22 months, interquartile interval 13-42 months) developed immunosuppression. Using a mathematical model of proportional Cox intensities, we tested anamnestic, clinical and laboratory parameters characterizing the state of health, HIV status of the mother, the course of pregnancy and childbirth, chemoprophylaxis of vertical HIV transmission, pathology of the neonatal period in children. Statistical significance in the multivariate model was demonstrated by the indicators «Lack of HIV vertical transmission chemoprophylaxis» (odds ratio 2,5; 95% confidence interval 1,4–7,7; P = 0,033) and «Congenital herpesvirus infection» (odds ratio 3,0; 95% confidence interval 1,3–6,9; P < 0,001).Conclusion. All children with HIV infection quickly developed immunosuppression. The independent factors influencing the timing of the immunosuppression development were the lack of HIV vertical transmission chemoprophylaxis and the congenital herpesvirus infection. The results of the study make it possible to recommend expanding the coverage of HIV-infected pregnant women and their children with three-stage vertical HIV transmission chemoprophylaxis and improving measures for the diagnosis and treatment of congenital herpesvirus infections.

The last fifteen years have been marked by rapid progress in the study of neutrophils. The discovery of transcriptional plasticity of neutrophils, their phenotypic and functional heterogeneity contributed to launching active interdisciplinary studies on the role of neutrophils in various chronic inflammatory diseases. Increased systemic circulation of immunosuppressive neutrophils can be observed not only in sepsis, but also in chronic systemic inflammation, which, along with disorders of lipid metabolism, is the major mechanism of atherosclerosis development and progression. Monocytes, dendritic cells, Tlymphocytes and neutrophils are key participants and modulators of inflammation in atherosclerosis. Potential significance of immunosuppressive neutrophils in atherogenesis and regulation of inflammatory response in atherosclerosis has not been currently established. However, taking into account their possible effects upon T lymphocytes and innate immunity cells, the study of immunosuppressive neutrophils seems promising in the context of atherosclerosis and atherosclerotic cardiovascular diseases. The purpose of this study was to evaluate relationship between the numbers of circulating immunosuppressive neutrophils and subpopulations of T cells and monocytes in the patients with subclinical atherosclerosis. The study enrolled patients aged 40-64 years with subclinical atherosclerosis of peripheral arteries. Subpopulations of neutrophils, lymphocytes and monocytes were phenotyped by flow cytometry using “Navios 6/2” (Beckman Coulter). 133 patients, 65 (48.8%) males and 68 (51.2%) females were included into the study. Correlation analysis showed that increased number of circulating CD16hiCD11bloCD62Lbr neutrophils was associated with increased number of regulatory T lymphocytes. The patients with subclinical atherosclerosis and absolute numbers of circulating immunosuppressive neutrophils within the first quartile (

Cytomegalovirus (CMV) infection is the most severe viral infection in renal transplant recipients, which can occur in the post-transplant period in both adult and pediatric recipients. Developing and applying an effective prevention and treatment strategy for pediatric renal graft recipients is a priority. Objective: to compare the effectiveness of the protocols used for the prevention of CMV infection in pediatric kidney transplant recipients.Materials and methods. The study enrolled 118 patients who underwent primary kidney transplantation at Shumakov National Medical Research Center of Transplantology and Artificial Organs. Based on retrospective analysis, all recipients were divided into two groups, depending on the prophylactic strategy after kidney transplantation. The followup period for pediatric kidney recipients ranged from 108 to 1803 (623.5 ± 379.5) days. CMV infection activity was monitored by polymerase chain reaction.Results. The frequency of CMV infection activation episodes at 3 and 6 months was independent of the prophylaxis strategy used. The recurrence rate of CMV infection one year after surgery was significantly lower (p = 0.037) with Strategy 2. No cases of CMV syndrome or CMV disease, graft dysfunction, or chronic rejection associated with CMV infection were reported. Increasing the dose of antiviral drugs in Strategy 1 did not increase the risk of cytotoxicity and nephrotoxicity, which are reversible (creatinine levels were not significantly different in the study groups at 3, 6, 12 months, p = 0.542, p = 0.287, p = 0.535, respectively). The incidence of kidney graft rejection did not increase in patients with lower doses of immunosuppressants in Strategy 2.Conclusion. Both prophylactic strategies are effective in pediatric kidney recipients. However, the choice of a strategy depends on the individual characteristics of the patient and requires a personalized approach.

The review includes the results of analytical research on the problem of application of pancreatic islet encapsulation technologies for compensation of type 1 diabetes. We present a review of modern encapsulation technologies, approaches to encapsulation strategies, insulin replacement technologies: auto-, allo- and xenotransplantation; prospects for cell therapy for insulin-dependent conditions; modern approaches to β-cell encapsulation, possibilities of optimization of encapsulation biomaterials to increase survival of transplanted cells and reduce adverse consequences for the recipient. The main problems that need to be solved for effective transplantation of encapsulated islets of Langerhans are identified and the main strategies for translating the islet encapsulation technology into medical reality are outlined.

Introduction. The pandemic caused by the SARS-CoV-2 coronavirus is characterized by significant morbidity and mortality. Kidney transplant recipients are at high risk of a more severe course of coronavirus infection due to ongoing immunosuppression, a high comorbidity index, and elder age.Aim. To investigate the features of the clinical course, the treatment applied and also the outcomes of the new coronavirus infection in patients after kidney transplantation.Material and methods. The retrospective study included 69 adult kidney transplant recipients continuously followed-up by our transplant nephrology service and who fell ill with COVID-19 from April 2020 till February 2021. The comparison study of the clinical pattern, laboratory and instrumental test results, treatment features and outcomes was made.Results. The most common clinical symptoms were hyperthermia (85.5%, n= 59), weakness (65.2%, n=45) and cough (52.2%, n=36), other symptoms were significantly less common. In 89.5% of cases (n=60), the virus ribonucleic acid was detected at least once by polymerase chain reaction; in 10.5% of cases (n=7), the polymerase chain reaction results were negative. According to CT, the extent of lung tissue lesion was identified as CT1 stage in 28 patients (46.7%), CT2 stage in 24 (40%); and only in 8 (13%) patients the lesion was assessed as CT3. Later on the number of patients with more than 50% lung damage increased to 16 (26.7%) and in 1 case the severity of lung tissue damage was consistent with CT4. Typical features for all patients were anemia and lymphopenia of varying severity, hypoproteinemia, increased serum creatinine and urea, C-reactive protein, ferritin, procalcitonin and D-dimer in the laboratory test results. The treatment included antiviral, antibacterial, anticoagulant therapy, corticosteroids, biological anti-cytokine drugs. In 95% of cases (n=66), the maintenance immunosuppressive therapy was changed up to complete withdrawal of the certain components. The patient survival rate with a functioning graft was 76.8% (n=53), the graft loss was observed in 4.3% of cases (n=3), and the lethal outcome was reported in 18.8% (n=13). The cause of death was a severe respiratory distress syndrome with multiple organ dysfunction complicated by sepsis and septic shock in 8 patients (61.5%). Invasive ventilation and hemodialysis were associated with 17.2 (p

Background. The growth of antibiotic resistance of Helicobacter pylori, a microorganism significant in the development of gastrointestinal diseases and inflammatory periodontal diseases, makes us think about the search for new approaches to the eradication of the microorganism. One solution to this problem may be to develop immunobiological preparations based on microorganisms inactivated with colloidal silver nanoparticles (CSNPs).The aim. To evaluate the inactivating ability of colloidal silver nanoparticles in vitro and in vivo with respect to H. pylori to determine the possibility of their use in the development of a specific immunobiological preparation.Materials and methods. The study design consisted in sequential execution of the steps of synthesis of colloidal silver nanoparticles with an assessment of the conditionality of the prepared preparations; isolating and identifying pure H. pylori culture; inactivation of H. pylori by synthesized silver nanoparticles; evaluation of the result of H. pylori inactivation in vitro and in vivo.Results. The conditionality of the synthesized colloidal silver nanoparticles of size 30 ± 3 nm, obtained using a step-by-step technique, was estimated by electron microscopy. Testing the inactivating activity of CSNPs on H. pylori showed that their effect on the culture for 3 hours at a ratio of volumes of CSNPs and 1:1 culture leads to a gradual decrease in the concentration of the microorganism until its complete death and lack of growth on the fifth passage. During the evaluation of the effect of CSNPs on H. pylori, it was shown that the inactivated culture retains its cultural and tinctorial properties; alters morphological properties and biochemical activity; becomes more sensitive to antibiotics and L. acidophilus; ceases to establish in the body of mice with an immunosuppression condition.Conclusions. Proposed method of synthesis of silver nanoparticles with proven inactivating activity against H. pylori can become a stage of biotechnological process of development of vaccine preparation both on the basis of given microorganism and in complex with CSNPs possessing multilevel antimicrobial effect, antioxidant and immunomodulating activity.

The differential diagnosis of intestinal tuberculosis and Crohn’s disease is a difficult task for most specialists due to their high similarity in clinical manifestations, instrumental diagnosis and histological pattern.The aim: to consider the clinical and diagnostic features of intestinal tuberculosis and Crohn’s disease, to show the role of various methods of their diagnosis (CT of the abdominal cavity, CT-enterography, colonoscopy with biopsy).A clinical example shows a case illustrating the difficulties of diagnosing intestinal tuberculosis, initially diagnosed as Crohn’s disease. The features of the course, complex diagnosis and treatment of intestinal tuberculosis and its complications during immunosuppression are demonstrated. At the first stage of treatment, the patient’s data related to CT of the chest organs, colonoscopy and histological examination of biopsy samples were incorrectly interpreted. As a result, a wrong diagnosis of Crohn’s disease was made, and immunosuppressive therapy was prescribed that provoked a generalization of the existing tuberculosis process. Subsequently, repeated surgical interventions were performed for complications of intestinal tuberculosis – perforation of tuberculous ulcers, peritonitis. Based on the analysis of the literature data and our own observation, it is shown that granulomatous inflammation in the study of intestinal biopsies doesn’t always allow us to make a clear diagnosis, first of all, there are intestinal tuberculosis and Crohn’s disease in the differential diagnostic series. The use of histobacterioscopy according to Ziehl – Neelsen, the study of fecal matter by luminescent microscopy, as well as molecular genetic methods for detecting DNA MTB allow us to verify the diagnosis. If Crohn’s disease is misdiagnosed as intestinal tuberculosis, then the prescribed anti-tuberculosis therapy can cause harm and lead to a delay in the underlying disease treatment. The reverse misdiagnosis is potentially more dangerous: if tuberculosis is misdiagnosed as Crohn’s disease, then the appointment of immunosuppressive therapy can lead to the generalization of tuberculosis and the development of fatal complications.

Immunosuppressive therapy – therapy to suppress undesirable immune reactions of the body, is mandatory and lifelong after an organ transplantion. The risk of oral diseases increases against the background of continuous immunosuppressive therapy. The article presents the most common complications of immunosuppressive treatment in the oral cavity. These are, first of all, diseases of the oral mucosa caused by a fungal, bacterial or viral factor, such as oral hairy leukoplakia, stomatitis, erosive-ulcerative lesions, hyperkeratosis, exudative multiform erythema as well as diseases of marginal periodontium, xerostomia and dental caries. To ensure a high level of dental health after the organ transplantation operation, dispensary observation and timely diagnosis of diseases of the oral cavity are necessary.

Primary (hematogenic) peritonitis caused by non-tuberculosis mycobacteria is extremely rare in the clinical practice. The main number of reported episodes of primary intraabdominal infection is associated with M. tuberculosis and the development of granulomatous inflammation of the peritoneum visually similar to carcinomatosis. The vast majority of reports of peritonitis associated with non-tuberculosis mycobacteria are interlinked with chronic peritoneal dialysis or foreign bodies of the abdominal cavity, when an infection is carried out by the contact through a dialysis catheter, prosthesis or a gastric banding device. The article describes a clinical case of peritonitis and splenitis caused by M. avium with hematogenic spread of infection from the primary pulmonary focus in a young patient with immunosuppression. Diagnosis of such peritonitis at the preoperative stage is extremely difficult due to the similarity of symptoms with atypical appendicitis or infected ascites. The intraoperative picture also did not allow us to assume a mycobacterial etiology of the process, and the absence of a focal point of peritonitis made it necessary to thoroughly understand the situation. Only a peritoneal biopsy and a complete laboratory examination of exudate allowed us to verify the diagnosis, to understand the pathogenetic mechanisms of the disease and to start a timely etiotropic therapy.

In this review of current publications, we look at the molecular mechanisms of tolerance of the liver and its allografts in terms of minimization and possibilities of withdrawing immunosuppressive therapy, mainly in the long-term period after liver transplantation. Information about clinical trials with regulatory T cells (Tregs) for the purpose of tolerance induction is presented. Data from a new consensus study on individualization of immunosuppressive therapy regimens are presented. Options for possible withdrawal of immunosuppression both in the early and in the long term after liver transplantation (LT) are considered. We suggest a way to study the lymphoproliferative potential of a liver transplant recipient to be investigated, since not only rejection determines life expectancy, but also the degree of immunosuppression effect on bone marrow depending on patient age.

Feline viral leukemia is an infectious disease that is common throughout the world. Despite the statistical records that have been successfully kept in other countries for many years, there is little data on the prevalence of the infection in the Russian Federation, and the samples are represented by a small number of animals. 11,807 blood samples collected in Moscow and the Moscow Oblast were tested for FeLV antigen and antibodies against FeLV by polymerase chain reaction, enzyme immunoassay, and immunochromatographic assay. The prevalence of feline viral leukemia was 12.8%, which correlates with the prevalence of the disease detected in developing countries, and speaks of a high disease prevalence in domestic cats in Moscow and the Moscow Oblast. Most often, feline leukemia virus was detected in free roaming domestic cats. During the diagnostic studies, the following hematological abnormalities were found: anemia, thrombocytopenia, lymphopenia, and a shift of the leukocyte formula to the left. Biochemical blood tests showed the increased levels of total protein, aspartate aminotransferase, alkaline phosphatase, and C-reactive protein. The obtained data demonstrate non-specific hematological and biochemical abnormalities in infected cats, and dictate the need for further study of the risk factors that predispose cats to the infection with this viral disease. Feline viral leukemia should be suspected in case of a non-specific clinical picture, as well as in case of abnormalities in blood biochemical and hematological parameters of free roaming cats or of those which have had a confirmed contact with their conspecifics.

Background. Focal segmental glomerulosclerosis (FSGS) of the graft in kidney recipients is a rare and difficultto-diagnose post-kidney transplant complication, which can lead to graft loss and death of the recipient. A unified protocol is required for the treatment of this disease.Materials and methods. A 15-year-old female patient C. diagnosed with stage 5 chronic kidney disease as a result of steroid-resistant nephrotic syndrome with hematuria underwent a living related-donor kidney transplantation. On the third day after the operation, laboratory and imaging data showed kidney graft dysfunction. Patient examinations established the cause of the graft dysfunction – idiopathic nephrotic syndrome in FSGS.Results. For the treatment of recurrent FSGS, the patient had her immunosuppressive therapy converted from tacrolimus to cyclosporin A, and received two 500 mg rituximab injections. Ten sessions of therapeutic plasma exchange (Plasauto Sigma) were performed to remove antibodies to podocytes. During the therapy, diuresis was restored, creatinine and urea levels decreased. Six months after the kidney transplant, graft function was fully restored. Conclusion. The absence of recurrent FSGS within six months during a single course of therapeutic plasma exchange with its subsequent cancellation after restoration of graft function allows to recommend the developed method for the treatment of FSGS in pediatric patients after kidney transplantation.

Introduction. The lifelong use of calcineurin inhibitors in liver transplant recipients leads to an increased incidence of chronic kidney disease.Objective. To compare the changes in glomerular filtration rate over five years in liver transplant recipients between those on everolimus with a reduced exposure to calcineurin inhibitors and those on standard doses of calcineurin inhibitors.Material and methods. Fourteen liver transplant recipient switched to everolimus with a minimization of calcineurin inhibitors exposure in the first months after liver transplantation from February 2009 to February 2015 who had received that therapy continuously for at least 60 months were included in the case-control study. Twenty eight liver transplant recipients (matched by sex, etiology of the underlying disease, calcineurin inhibitors) who were followed-up for at least 60 months after liver transplantation, who had received no dose of everolimus, in whom the glomerular filtration rate could be calculated at all points of analysis were selected as a comparison group (1:2). Glomerular filtration rate was calculated immediately before liver transplantation; 12, 24, 36, 48, and 60 months after liver transplantation. The glomerular filtration rate after liver transplantation was also calculated for liver transplant recipients from the main group immediately before the conversion to everolimus.Results. Before liver transplantation, the median of glomerular filtration rate in the main group of liver transplant recipients was lower (81.2 ml/min) than in the comparison group (97.5 ml/min, p=0.01). After liver transplantation, the renal function worsened in both groups of patients. In a pairwise comparison, the medians of glomerular filtration rate were statistically significantly lower after 12 months, 24 months, 36 months, 48 months after liver transplantation, than before liver transplantation. The median of glomerular filtration rate at the time of immunosuppression conversion was 44.3 ml/min. After the conversion of immunosuppression, the median of glomerular filtration rate gradually increased, and after 36 months the differences in glomerular filtration rate reached statistical significance compared with the level before conversion (69.4 ml/min;p=0.048). These differences still increased after 60 months after conversion (72.3 ml/min; p=0.041).Conclusion. Long-term administration of everolimus with minimization of calcineurin inhibitors exposure with the early conversion to this immunosuppression regime provides a steady improvement in renal function in liver transplant recipients with a low glomerular filtration rate in the preoperative and early post-transplant period.

Squamous cell carcinoma of the skin, or cutaneous squamous cell carcinoma (CSCC), is the second most frequent type of skin cancer, and its incidence continues to rise all over the world. Usually has a benign clinical behavior, but it can be presented as locally invasive and metastatic aggressive tumor with 2% mortality rate. Nowadays, new risk factors for have appeared, that form pharmacologically-induced CSCC after immunosuppressant drugs used for organ transplantation, or BRAF inhibitors used for melanoma. In recent years we have got a new information about the role of mutational burden, signaling pathways involved in CSCC development and new possibilities and molecules for targeted therapy. Better understanding of the immune system functioning and benefits of immunotherapy with immune checkpoint inhibitors (PD-1) for CSCC that has changed the therapeutic approach. According to recent clinical trials data, new treatment options with PD-1 inhibitors achieved a response rate of 50% for locally advanced CSCC and 47% for metastatic CSCC, including 16.1% complete remissions. This review focuses on the molecular profile, targeted therapies and immunotherapy for locally advanced and metastatic CSCC.

Objective: to investigate the effectiveness of long-term oral administration of Actovegin in post-COVID patients with cognitive impairment (CI).Patients and methods. 444 patients (142 men, 302 women) with COVID-19 and CI participated in the study. One-half of the included participants – 222 patients (70 men and 152 women) – were prescribed with actovegin 400 mg 3 times a day in addition to the baseline therapy; 222 patients (72 men and 150 women) were randomized to the control group. Cognitive functions were assessed with Montreal Cognitive Assessment (Montreal Cognitive Assessment test, МоСA test), fatigue – with Multidimensional Fatigue Inventory (MFI-20), emotional disturbances – with Spielberger-Hanin test.Results and discussion. Post-COVID patients with CI in the Actovegin group after 60 days follow-up had higher mean MoCА scores (p

The pandemic of HIV infection, tuberculosis and sexually transmitted infections is characterized by the formation of multicomorbid conditions. The coexistence of pathogenetically interrelated and interdependent epidemics of different infections developing in an environment conducive to their spread is described by the term “syndemia”, which can be observed in relation to HIV infection, tuberculosis and syphilis. On the example of clinical observation, the difficulties of managing a rare case of tuberculosis and syphilis against a background of HIV infection are described. Clinical, radiological and laboratory features of this mixed infection are considered. The role of radiological diagnostic methods for the detection of HIV-associated tuberculosis in case of negative results of bacteriological tests are substantiated. The progression of the specific process, opportunistic infections and side effects on combination therapy with severe immunosuppression make the treatment of this category of patients extremely difficult. Due to the increase in the spread of tuberculosis and syphilis among HIV-infected people, close attention should be paid to screening patients at risk of infection. Introduction of effective preventive and anti-epidemic measures is also required. The outlined phased diagnostic process is of practical importance for specialists of various fields.

The purpose of the study is to evaluate the effect of Gentiana algida Pall dry extract on microanatomy of CBA mice thymus at azathioprine immunosuppression. Material and Methods. Experiments were carried out on CBA male mice. Immune deficiency was modeled by intragastrical administration of azathioprine in the dose 50 mg/kg once a day for 5 days. The G.algida dry extract in the dose 50 mg/kg was administered to animals for 15 days against azathioprine. Morphological studies of the thymus were carried out on day 21 after the azathioprine administration. The area of the thymic lobule, the cortex and the medulla; the width of the cortex; the thickness and length of the medulla; the thickness of the capsule; the density of cells in the subcapsular zone and the deep layers of the cortex were measured using the Axio Vision SE64 Rel.4.8.3 image analysis program. The cellular composition was determined in the subcapsular and central zone of the cortex. Results. The G.algida extract limited the development of involutive changes in the thymus caused by cytostatic azathioprine: the cortex area was 16% higher and medulla area 17% lower compared with the control group. The ratio of cortex and medulla in experimental group was 1.4 times higher than that in the control group. The G.algida extract increased verage density of cells by 30% in the subcapsular zone. The number of blasts and large lymphocytes increased on average by 2.0 times in the deep layers of the cortex, and in the subcapsular zone - by 4.3 and 2.4 times, respectively, compared with those in control group. Conclusions: G.algida extract limited the development of pronounced involutive processes in the thymus at azathioprin immunosuppression (increased the mitotic activity of thymocytes, reduced the severity of destructive processes and prevented the growth of adipose tissue).

Acute respiratory infections are the most common reason to consult a paediatrician. Children, especially during critical periods of immune response, are one of the most vulnerable groups to infections. The prevention of recurring respiratory infections is very important, especially from the beginning of attending pre-school and school facilities. Since ancient times, preventive measures such as rational daily routine, sufficient physical activity, correction of nutritional status, phytotherapy and homeopathic treatment have been used. In recent years these children have been optimising their vitamin D status and taking antioxidant vitamins, micro- and macronutrients. To date, as a result of innovative research on the human microbiome, information has emerged on its impact on the human body as a whole. The connection of the intestinal microbiota with the brain (gut-brain axis), with the respiratory tract (gut-lung axis), the cardiovascular system, kidneys and even mental health has been proved. The use of multistrain and multispecies probiotics in the prevention of recurrent infections in children opens up new opportunities to influence the child’s immune response and to form food tolerance. Today, a new multistrain multispecies probiotic (manufacturer ADM Protexin, UK) for the prevention of recurrent respiratory infections in children has appeared on the market. Studies have shown that using several strains of lactobacillus contained in this probiotic leads to more consistent results than monostrains and placebo in the prevention of respiratory diseases.Given the problem of antibiotic resistance, especially in young children, the new possibilities of preventing acute respiratory diseases in children using multistrain and multispecies probiotics make it possible not only to reduce the number and severity of episodes of acute respiratory infections, but also to reduce the frequency of antibiotic use.

Background. Cancer occurring in recipients of living donor liver transplantation may be characterized by a progressive course requiring an immediate specialized treatment initiation and adjustment of immunosuppression regimen. Aim. To specify the malignancy development mechanisms and risk factors in the recipients of living donor liver transplantation. Material and methods: 275 living donor liver transplantations were made in Burnasyan Federal Medical Biophysical Center of FMBA from 2010 to 2020. Forty two (15.27 %) patients underwent surgery for hepatocellular carcinoma. The median time to the onset of malignancy development was estimated. The incidence of malignancy in general population and in recipients of living donor liver transplantation was compared. Results. The development of neoplastic lesion was registered in 9 cases (3.27%). Malignances were detected in 8 cases (2.90%). Median time to the onset of malignancy development was 48 months. 1, 3, and 5 year overall survival rates were 97%, 96%, 94%;respectively; 1, 3, and 5 year survival rates after transplantation for hepatocellular cancer were 97%, 91%, 91% respectively. Survival rate of patients with De-novo malignancy was 90%. Conclusion. Recipients of living donor liver transplantation have an increased risk of malignancy development that requires a close long-term follow-up.

Aim of review. We review published evidence on the torque teno virus (TT virus, TTV), which was discovered in the late of the 20th century.Key points. TTV is frequently confirmed in patients with hepatitises of viral origin or no definite viral aetiology, as well as in healthy people. Particular biochemical and histological changes in hepatic tissue and bile duct epithelium are reported for TTV monoinfection, which suggest viral replication in hepatocytes. At the same time, no cytopathic effects inherent in pathogenic hepatotropic viruses were revealed in hybridisation assays with TTV-infected cells. Novel data incited novel opinions on the TTV interaction with human. Earlier views of hepatotropic TTV gradually changed with newer evidence on its dispersion and coinfection with other viruses, including known hepatitis agents. Polytropism of TTV disproves its exclusive attribution to hepatitis viruses. High prevalence of the virus in human population argues in favour of its non-pathogenic persistence in the human viriome. TTV DNA content in blood is proposed as an endogenous immune status marker to observe prior to organ transplantation.Conclusion. High TTV dispersion in human population suggests its persistence in the human viriome. Seldom observed damaging effect of TTV on hepatic cells and bile duct epitheliocytes may indirectly suggest its opportunistic pathogenic properties.

COVID-19, formerly coronavirus infection 2019-nCoV, is a potentially severe acute respiratory infection caused by the SARS-CoV-2 coronavirus (2019-nCoV). It is a dangerous disease that can occur both in the form of a mild acute respiratory viral infection and in a severe form with the development of bilateral polysegmental viral pneumonia, specific complications of which may include acute respiratory distress syndrome, resulting in the respiratory failure with a high risk of death. Due to the absence of etiotropic therapy for the coronavirus infection, pathogentic treatment becomes of primary importance. We present a clinical case of a severe form of COVID-19 in a 33-year-old man to whom we administered a new method of pathogenetic treatment of this disease based on immunosuppresiive therapy followed by therapeutic plasma exchange and infusion of non-specific human immunoglobulin.

Aim. An evaluation of the effectiveness of immunosuppressive therapy (IST) and tonsillectomy (TE) in patients with IgA nephropathy (IgAN). Materials and methods. A retrospective cohort of the study included cases with biopsy proven primary IgAN (n=367, age 3412 years, men 55%). We used demographic and clinical and morphological parameters at the time of biopsy. Median followup period was 26 (10; 61) months. Outcomes were remission (complete or partial) and the progression of IgAN (defined as the start of dialysis or a decrease in glomerular filtration rate 50% from baseline). All patients received treatment with renin angiotensin system blockers. Evaluation of the effectiveness of therapy was carried out using propensity score (PS) methods matching, conventional double robust regression models with PS as independent covariate, and inverse probability weighting. Following patient subgroups were used for comparative analyses: with IST (n=176) and without IST (n=191); with TE (n=63) and without TE (n=304); without IST and without TE (IST-TE-; n=162); with TE and without IST (IST-TE+; n=29); with IST and without TE (IST+TE-; n=142); with IST and with TE (IST+ TE+; n=34). Results. All PS methods used gave close estimates of the comparative effectiveness of treatment in different subgroups: 1) patients on monotherapy with corticosteroids (CS) and combination of CS with other immunosuppressants did not have significant differences in probabilities of IgAN progression (hazard ratio 0.919; 95% CI 0.3332.950) and remission (odds ratio 0.919; 95% CI 0.3792.344) and were further combined into a group of IST; 2) IST was significantly associated with the lower risk of disease progression and increased odds ratio for remission; 3) the positive effects of IST were limited to cases with proteinuria 2 g/24 h; 4) the likelihood of IgAN remission and progression did not differ significantly between TE+ and TE-, IST-TE+ and IST-TE- groups. There were no cases of disease progression in the IST+TE+ group. The cumulative renal survival was higher in the IST+TE+ group compared to IST+ TE- group (p=0.010), while the probability of remission did not differ. Conclusion. IST was associated with a lower risk of IgAN progression and increased probability of remission, while these effects of IST were limited to patients with proteinuria 2 g/24 h. TE in combination with IST is associated with an additional reduction in the risk of disease progression.

Various research has shown that non-melanocytic malignant skin lesion is one of the most common post-kidney transplant neoplasms. Multiple lesions and a more aggressive clinical course are more common in kidney transplant patients than in the general population. This paper presents a case of malignant skin neoplasms in a patient 10 years after cadaveric kidney transplantation. The patient received standard 3-component immunosuppression with satisfactory graft function (serum creatinine level remained at 157–178 μmol/L). Scalp neoplasm was removed. Histological examination revealed a morphological picture characteristic of basal cell carcinoma with squamous differentiation. Subsequently, a relapse of the skin neoplasm of the temporal region, as well as new lesions in the frontal region and the skin of the anterior chest wall, were discovered. Despite surgical treatment and close-focus x-ray radiation, the disease rapidly progressed and eventually led to death. Squamous cell carcinoma can progress very rapidly in patients after solid organ transplantation, despite ongoing combination treatment. Perhaps in such cases, it is worth cancelling immunosuppressive therapy completely and removing the kidney graft in order to control progression of the malignant tumor process.

We present a case of simultaneous laparoscopic bilateral nephroureterectomy, cadaveric kidney allotransplantation and performance of vesicostomy. This observation shows that patients with end-stage kidney disease, primarily caused by neurogenic bladder dysfunction, can be successfully treated via surgery. The course of early postoperative period and further rehabilitation did not differ significantly from that obtainable after standard kidney allotransplantation.

Aim: To evaluate the efficacy of immunosuppressive therapy (IST) and tonsillectomy (TE) in patients with high-risk IgA nephropathy (IgAN). Materials and мethods. The retrospective study cohort included cases with primary IgAN ( n =213, age 34±11 years, male 52%) at high risk of progression with clinical and morphological data collected. The follow-up was 26 (10; 61) months. The association of IST without TE (IST; n =141) or with TE (IST+TE; n =72) with the development of complete (PR), partial (PR) and overall (PR or PR, OR) remissions was investigated., Results: The incidence of achieving early PR or OR in the IST and IST+TE groups was 65.2% and 86.1%, respectively ( p =0.002). The probability of early PR or OR was significantly increased in the IST+TE group compared to IST [HR 1.714 (1.214-2.420) and HR 3.410 (1.309-8.880), respectively]. IST+TE was associated with a 3- to 4-fold increase in the likelihood of PR or OR at the end of follow-up [HR 2.575 (1.679-3.950) and HR 4.768 (2.434-9.337), respectively]. Analyses using pseudorandomisation methods yielded similar results., Conclusion: TE may be effective for remission induction in high-risk IgAN.

Studying the role of apoptosis of blood cells allows to determine more precisely the mechanisms of immunopathology in general, and immunosuppression - in particular. The aim of that research was to study morphological and molecular indicators of apoptosis of peripheral blood lymphocytes in mice infected with Trichocephalus muris and rabbits infected with Passalurus ambiguus to determine possible mechanisms of secondary immunosuppression development under chronisation of helminthiasis. Materials and methods. During the experiment, the animals were divided into the following groups: 1) intact mice (control group) - 15 ind.; 2) intact rabbits (control group) - 10 ind.; 3) mice infected with Trichocephalus muris (Schrank, 1788) - 60 ind.; 4) rabbits infected with Passalurus ambiguous (Rudolphi, 1819 ) - 30 ind. Blood from the tail vein of mice, and the ear vein of rabbits was used to prepare smears 1, 2, 3, 6, 7, 8 weeks after infestation. Light microscopy of blood smears stained by Romanovsky’s method [2] was applied for leucogram determination and investigation of morphological indicators of apoptosis. For molecular studies, mononuclear leukocytes were isolated from venous whole blood by density gradient centrifugation using Ficoll-Paque media (= 1,077 g / cm3, «Pharmacia», Sweden) [12]. The concentration of the pro-apoptotic protein caspase-3 and anti-apoptotic protein Bcl-2 was determined in lysates of lymphocytes by ELISA using kits Human Caspase-3 instant ELISA and the Human Bcl-2 ELISA of the company «Bender MedSystems GmbH» (Vienna, Austria). Results and discussion. The analysis of obtained data shows that at helminth infection of animals and under chronisation of helminthiasis, statistically significant changes occur within 8 weeks in the total number of leukocytes, the total number of lymphocytes and lymphocytes with morphological signs of apoptosis, as well as in pro-apoptotic protein caspase-3 and anti-apoptotic Bcl-2 protein. This comprehensive study convincingly shown that a gradual and significant increase in apoptotic activity of lymphocytes on the receptor and cellular levels is observed in animals in the period from the beginning of infestation up to the chronic stage of helminthiasis. This is manifested in the increased number of lymphocytes with morphological features of apoptosis against the background of the increased level of pro-apoptotic protein caspase-3, and the reduced level of anti-apoptotic protein Bcl-2.

In the 2000s, a scientific interest to the Far Eastern scarlet-like fever (FESLF) mainly recorded In Russia and Japanwas remarkably increased. Such clinical and epidemic manifestation of human pseudotuberculosis is related to a certain bacterial clonal lineage characterized by a specific plasmid profile (pVM82, pYV48), sequence type (2ST) as well as the yadA gene allele (1st allele). In our study we examined features of inflammatory changes characterizing plasmidassociated pathogenicity of the FESLF pathogen. In addition, organ histopathology in experimental animals infected intraperitoneally with Y. pseudotuberculosis strains of the four plasmid types 48+:82+; 48+:82-; 48-:82+; 48-:82-; and 48-:82- was investigated. It was found that the mortality rate in animals infected with Y. pseudotuberculosis H-5015 strain (82+:48+) bearing two plasmids with a molecular weight of 82 and 48 MDa was 40%. A picture of diffuse pneumonia with moderate inflammatory infiltration in pulmonary tissue and changes in lymphoid organs characterizing immunodeficiency we observed as early as 3 days postinfection (p.i.). On the contrary, animals infected with Y. pseudotuberculosis H-5015 strain (82+:48–) bearing a single plasmid 82 MDa pVM, mortality rate was 30%. A vascular reaction in the lungs and liver as well as deteriorated vascular destructive changes were revealed starting from day 3 and on day 5–7 days p.i., respectively, which was paralleled with perivascular infiltration mainly by mononuclear cells and focal pneumonia as well as a reaction of bronchialassociated lymphoid tissue and minimal organ destructive changes. On day 7 p.i., signs of granulomatous inflammation in the liver in a form of small mononuclear cell clusters and perivascular compact infiltrates were found. At all time points, lymphoid organ hyperplasia was noted. In case the infection caused by H-5013 strain (48+), the mortality rate was 80%. Inflammatory changes with dominant mononuclear cells were detected as early as 1 day p.i. associated with a picture of large focal bronchopneumonia, more pronounced in the non-survivor animals, also demonstrating signs of severe immunosuppression in the lymphoid organs. Starting from day 3 p.i., lymphoid hypoplasia in the spleen and lymph nodes was detected in all infected animals paralleled with pathogen-associated tissue damage in various organs. Animals infected with the plasmid-free H-5013 strain 48-) resulted in 25% mortality rate. Moreover, starting from day 3 p.i., a slight mononuclear inflammatory infiltration in the lungs and liver, a moderate giant cell reaction in the splenic pulp, and loose perinodal inflammatory infiltration in the lymph nodes were observed. Thus, while modeling infection caused by different plasmid types of Y. pseudotuberculosis, the data on differences in histopathology of changes in diverse organs regarding dynamics and generalization of the inflammatory response, as well as the severity of pathogen-associated damage in the lymphoid tissue were obtained. In case Y. pseudotuberculosis strains contained pVM82 plasmid with or without virulence plasmid pYV vs. single pYV-positive strains, an area of the inflammatory response as well as severity of immunosuppression manifested by splenic and lymph node delymphatization were decreased. It allowed to suggest that pVM82 plasmid found In Russia-originating Y. pseudotuberculosis strains might be implicated in limiting intensity of inflammatory response, bacterial dissemination and severity of lymphoid organ damage.

Objective: Assess the efficiency of highly active antiretroviral therapy (HAART) in patients in the late stage HIV infection Methods: The effectiveness of HAART in 29 patients with late diagnosed HIV infection was assessed. Rapid testing and immunoenzyme testing were used to confirm the presence of HIV infection. The formulation of the clinical diagnosis was based on the clinical classification of HIV infection approved by WHO (2013). According to the National Clinical Protocol for HIV Treatment, approved in the Republic of Tajikistan, after treatment of opportunistic infections, all patients were assigned specific therapy. Evaluation of the effectiveness of therapy was carried out taking into account immunological and virological criteria, on changes in the level of CD4 lymphocytes and viral load before the onset of HAART and after 6 months after taking the drugs. Results: All patients were examined and diagnosed with the IV clinical stage of HIV infection. Immunosuppression rate – the level of CD4 lymphocytes – at the time of the onset of HAART in all the study was less than 50 cells/μl. 16 (55.2%) patients received a HAART scheme consisting of tenofovir, emtricitabine, efavirenz (Viraday) in standard doses, 13 (44.2%) patients received abacavir, lamivudine, and lopinavir/ritonavir or atazanavir/ritonavir. During the study, 11 (37.9%) patients were fatal during 1-3 months of HAART. The causes of the fatal outcome were pulmonary tuberculosis, Kaposi sarcoma, multiple organ dysfunction syndrome, meningoencephalitis. In the surviving patients (n=18) after 6 months of the beginning of therapy, there was an increase in the level of CD4 lymphocytes on average by 129,4±5,2 cells/μl, of which only 8 (27.6%) patients had virological effect – the viral load level was less than 1000 copies/ml of blood. Conclusion: Therapy was effective in 8 (27.6%) patients under investigation. The death of 37.9% patients is due to the late diagnosis of HIV infection, the onset of HAART with deep immunosuppression and the development of inflammatory immunity recovery syndrome.

Purpose: to study the role of cellular immunity in the development of retinopathy of prematurity (ROP).Material and methods. 87 children were tested, including 60 with III — V stage ROP and posterior aggressive retinopathy that had gestational age from 25 to 32 weeks at birth, aged 1 month to 1 year (study group) and 27 healthy children of the same age (control group).Results. No statistically significant differences of immunological parameters were revealed within the groups of children aged 1 to 3 months, 3.5 to 6 months, and 6.5 to 12 months. The gestational age at birth had no effect on the parameters studied. With increasing severity of ROP amid reduced indicators of T-regulatory cells, the number of B-cells (CD19 +) grew, T-natural killer cells (CD3 -/CD16 +CD56 +) reduced significantly (p < 0.05), and the number of CD4+ T-cells reduced showing the significance of (p < 0.01–0.05).Conclusion. The obtained data testify to the emergence of autoimmune reactions and a decrease in the level of regulatory T-cells in a premature child, more pronounced in severe stages of ROP.

Kidney transplantation is the most effective treatment for the end-stage chronic renal disease that has been observed to increase in the incidence consistently in recent years. Despite the achievements in immunosuppressive therapy in patients after renal transplantation, the graft survival length has remained unchangeable during the recent few decades. Bone marrow multipotent mesenchymal (stromal) stem cells (BM MMSCs) are known as a potential tool to influence this situation. Since their discovery in the middle of the XX century, their wide therapeutic potential in the transplantation of solid organs was demonstrated both in experimental and clinical trials. They have the ability to modify recipient’s immune response and improve postoperative course, however, having a low level of their own immunogenicity. MMSCs realize their properties through interactions both with the innate and adoptive immune system. Meanwhile, actual questions such as an optimal dosage and injection timing are still need answers. Actual experience of both experimental and clinical use of MMSCs in kidney transplantation has been analyzed in the present publication.

Abstract The article discusses the main basic immunological changes among patients with community-acquired pneumonia (CAP) and cytomegaloviral infection (CMVI), the group is compared with control one and with CMVI-negative individuals. The research data are used for diagnostic approach optimization on the part of immunology among immunocompetent young patients and CAP-prognosis (by PORT scale) according to CMVI occurrence and persistence. The aim is to recognize the main cell and humor disturbances in immunological reactivity among CAP-patients with CMVI persistence and their influence on CAP course and prognosis. Materials and methods. One hundred and five CAP-patients (51 (48.6 %) males, 54 (51.4 %) females) and 61 healthy individuals (26 (42,6%) males, 35 (57.4 %) females) have been examined according to clinical, laboratory and instrumental standards regulated by the MH of Ukraine. All responders were additionally studied for CMVI persistence (CMV IgM, CMV IgG, CMV IgG-avidity) and immunological test of cellular (CD3, CD4, CD8, CD22) and humoral (IgA, IgM, IgG) immunity. Results. CMVI persistence was prevailed significantly higher (P = 0.003) among the CAP-patients (80 (48.2 %) patients) than in the control group (34 (20.5 %) responders) and was mostly characterized by high avidity level (51 (48.6 %) patients (P = 0.007)). The percentage of CD22 increased with age among the CAP-patients (χ2 = 8.479; P = 0.037) and made up (15.5 ± 7.19) % in the group of 18–20 years old compared to the group of 30–39 years old – (22.07 ± 6.06) %. The healthy individuals were characterized by CD4 decreasing with age (χ2 = 8.585; P = 0.037). The number of respondents with decreased levels of CD4 (P = 0.032), IgA (P = 0.005), IgM (P = 0.018), IgG (P = 0.009) was significantly higher among the CAP-patients than in the control group. Decrease in СD3, CD4, CD8 values was statistically significant with CAP severity increasing by PORT score (P < 0.0001). CD3 ((47.353 ± 1.503) %) and CD4 ((27.137 ± 0.992) %) levels were significantly higher in the CAP-group patients with high CMV IgG-avidity than in those ones with moderate ((46.174 ± 2.044) % and (25.696 ± 0.944) %, respectively) and low avidity ((39.429 ± 1.730) % and (22.429 ± 1.837) %, respectively) (P < 0.0001). The amount of lymphocytes, CD4, CD8 was significantly lower among the CMV-positive CAP-patients. Their deficiency progressed with the mortality risk score by PORT. Conclusions: The CMV-positive CAP-patients differ statistically significantly by immunological reactivity from CMV-negative respondents and healthy ones (P < 0.05). The progression of cellular (lymphocytes, CD3, CD4, CD8, CD22) and humoral (IgA, IgM, IgG) immunosuppression depends on the duration of CMV persistence (by avidity level) and CAP severity level (by PORT score).

History of heart transplantation in combination with immunosuppressive therapy and acute viral respiratory infection overlay makes the patient difficult to manage. In case of COVID-19, the setting is complicated by unknown pathogenesis, including its effect on blood, coagulation system, and lung tissue. Current case report discusses the 60-year-old patient with a COVID-19 infection occurred in the immediate postoperative period after heart transplantation.

Background. Kidney transplantation efficacy is limited by immunosuppression nephrotoxicity, antibody-mediated and chronic rejection. Avoiding immunosuppression nephrotoxicity is a promising strategy to improve long term outcomes. Belatacept, a synthetic immunoglobulin which blocks CD28-B7 pathway of T-lymphocyte costimulation, is considered as an alternative to calcineurin inhibitors in maintenance immunosuppression since it has no nephrotoxicity. Purpose: to evaluate belatacept efficacy and safety for maintenance immunosuppression therapy after kidney transplantatin based on the clinical experience.Material and methods. From March 2017 to May 2018, we used belatacept in five kidney transplant recipients (one female and four males aged from 4 to 21 years) in the Kidney Transplantation Department of Petrovsky National Research Centre of Surgery Three kidneys were taken from related living donors, two kidney grafts were from deceased donors. Conversion from CNI to belatacept was performed between 6 and 112 month after transplantation. Patients were followed-up for average 12 months after conversion. We have described here these five cases, providing individual indications and the outcome of conversion.Results. The conversion failed in two children switched to belatacept with the purpose to improve compliance. Three patients switched to belatacept because of tacrolimus toxicity demonstrated good results in one year follow up.Conclusion. Belatacept demonstrated good results if was used instead of calcineurin inhibitors when the latter were poorly tolerated. The use of belatacept in multidrug immunosuppression in noncompliant patients was ineffective.

The kidney cannot be successfully grafted without immunosuppressive therapy. A unicenter retrospective study has evaluated the efficiency of immunosuppression with daclizumab (Zenapax) versus alemtuzumab (Campath).Subjects and methods. After renal allotransplantation, 64 patients, including 34 and 30 patients, were treated with daclizumab and alemtuzumab, respectively. The absolute count of peripheral blood lymphocytes was measured. Renal grafts were morphologically assessed as described by Banff.Results. After administration of alemtuzumab, there was a more pronounced decrease in the absolute count of peripheral blood lymphocytes and the rate of acute rejection crisis was 1.5 times lower than that after use of daclizumab.Conclusion. During the study, alemtuzumab demonstrated a more marked immunosuppressive activity than did daclizumab and the ability of the former to generate donor-specific immunotolerance in renal-allograft recipients.