Introduction: Primary immunodeficiencies (PID) are a group of rare genetic disorders with a multitude of clinical symptoms. Characterization of epidemiological and clinical data via national registries has proven to be a valuable tool of studying these diseases. Materials and Methods: The Russian PID registry was set up in 2017, by the National Association of Experts in PID (NAEPID). It is a secure, internet-based database that includes detailed clinical, laboratory, and therapeutic data on PID patients of all ages. Results: The registry contained information on 2,728 patients (60% males, 40% females), from all Federal Districts of the Russian Federation. 1,851/2,728 (68%) were alive, 1,426/1,851 (77%) were children and 425/1,851 (23%) were adults. PID was diagnosed before the age of 18 in 2,192 patients (88%). Antibody defects (699; 26%) and syndromic PID (591; 22%) were the most common groups of PID. The minimum overall PID prevalence in the Russian population was 1.3:100,000 people; the estimated PID birth rate is 5.7 per 100,000 live births. The number of newly diagnosed patients per year increased dramatically, reaching the maximum of 331 patients in 2018. The overall mortality rate was 9.8%. Genetic testing has been performed in 1,740 patients and genetic defects were identified in 1,344 of them (77.2%). The median diagnostic delay was 2 years; this varied from 4 months to 11 years, depending on the PID category. The shortest time to diagnosis was noted in the combined PIDs-in WAS, DGS, and CGD. The longest delay was observed in AT, NBS, and in the most prevalent adult PID: HAE and CVID. Of the patients, 1,622 had symptomatic treatment information: 843 (52%) received IG treatment, mainly IVIG (96%), and 414 (25%) patients were treated with biological drugs. HSCT has been performed in 342/2,728 (16%) patients, of whom 67% are currently alive, 17% deceased, and 16% lost to follow-up. Three patients underwent gene therapy for WAS; all are currently alive. Conclusions: Here, we describe our first analysis of the epidemiological features of PID in Russia, allowing us to highlight the main challenges around PID diagnosis and treatment.

центр экстренной и радиационной медицины им. А.М. Никифорова» МЧС России; 194044, г. Санкт-Петербург, ул. Академика Лебедева, 4/2, Российская Федерация Корниенко Елена Александровнад-р мед. наук, профессор, заведующая кафедрой гастроэнтерологии факультета последипломного и дополнительного профессионального образования 1

Monocytes play a key role in the development of immune response in bacterial infection, because of their phagocytic, antigen-presenting and secretory functions. There are three subpopulations of monocytes: “classical” CD14+CD16-, “intermediate” CD14+CD16+, and “nonclassical” CD14+dimCD16+. These monocyte subtypes have different phenotypes and functions. The ratio of appropriate subpopulations varies with development of the antibacterial response. The aim of the present research was to study phenotypes of the monocyte subpopulations in the patients with sepsis, and changes in the monocyte subpopulation ratio, depending on the presence of bacteria in circulating blood of the patients, as well as to estimate contribution of the monocyte subpopulations to the cytokine production. We observed 16 patients with sepsis (10 men and 6 women; mean age, 58±14 years, SOFA 9.4±2.1; a total of 44 blood samples) examined in dynamics. The control group included healthy adults (n = 23, 12 men and 11 women; mean age, 51±13 years). Laboratory studies included bacteriological cultures, determination of absolute and relative numbers of subpopulations of classical, intermediate and non-classical monocytes and their expression of HLA-DR and CD64, determination of IL-6, TNFα, IL-1β, IL-10 concentration in blood serum. Absolute number of monocytes was increased in the sepsis patients, the ratio of classical monocytes was also increased, like as relative and absolute numbers of  intermediate cells. Meanwhile, the subpopulation of non-classical monocytes did not change significantly. The monocyte subpopulation ratio depended on the presence of bacteria in blood, i.e., a higher proportion of intermediate cells was observed in the samples positive for bacteria in blood cultures. The ratio of subpopulations was restored after elimination of bacteria from the circulation. The expression density of LPS receptor (CD14), IgG receptors (CD16 and  CD64) was found to be increased, especially in the subpopulations of intermediate and nonclassical monocytes. In all subpopulations of monocytes, expression of HLA-DR is reduced, most notably in classical monocytes, least in intermediate cells. There was a significant increase in serum levels of IL-6, IL-1β, TNFα and IL-10 cytokines. Direct correlation between the absolute number of classical monocytes and IL-6 concentration was revealed, as well as intensity of multiple organ dysfunction. Increase in absolute amount of classical monocytes and IL-6 concentration might serve as an indirect criterion for evaluation of endothelial activation, an active producer of IL-6 and myeloid cell growth factors. A direct correlation between the percentage of CD14+CD16+ cells and IL-10 concentration in blood serum indicates to an important role of intermediate monocytes in IL-10 production. IL-10 suppresses the antigen-presenting function of intermediate cells, namely, expression of HLA-DR molecules, as suggested by inverse correlation between the IL-10 concentration and HLA-DR expression density on CD14+CD16+ cells. We have also determined an inverse correlation between the degree of multi-organ dysfunction  and relative amount of HLA-DR+ monocytes. The larger was a classical monocyte subpopulation, the more noticeable was a decrease of this index. The studies in ratios of monocyte subpopulations help to understand the mechanisms of antibacterial protection in sepsis. Monitoring of classical monocyte numbers and serum concentrations of IL-6 is necessary for a comprehensive assessment of inflammatory response in sepsis. Determination of HLADR expression on monocytes allows us to evaluate the intensity of immune suppression in critically ill patients.

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Objective. To develop methods for a rapid distance computer diagnosis of COVID-19 based on the analysis of breath sounds. It is known that changes in breath sounds can be the indicators of respiratory organs diseases. Computer analysis of these sounds can indicate their typical changes caused by COVID-19, and can be used for a rapid preliminary diagnosis of this disease. Materials and methods. The method of fast Fourier transform (FFT) was used for computer analysis of breath sounds, recorded near the mouth of 14 COVID-19 patients (aged 1880 years) and 17 healthy volunteers (aged 548 years). The frequency of breath sound records ranged from 44 to 96 kHz. Unlike the conventional methods of computer analysis for diagnosis of diseases based on respiratory sound studying, we offer to test a high-frequency part of FFT (20006000 kHz). Results. While comparing the breath sound FFT in patients and healthy volunteers, we developed the methods for COVID-19 computer diagnosis and determined the numerical criteria in patients and healthy persons. These criteria do not depend on sex and age of the examined persons. Conclusions. The offered computer methods based on the analysis of breath sound FFT in patients and volunteers permit to diagnose COVID -19 with relatively high diagnostic parameters. These methods can be used in development of noninvasive means for preliminary self-express diagnosis of COVID-19.

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Как известно, в патогенезе синдрома «сухого глаза» (ССГ), наряду с первичным дефицитом жидкости в конъюнктивальной полости, большое значение имеет повышение осмолярности прероговичной слезной пленки [1]. Так называемый гиперосмотический стресс в свою очередь служит важным звеном патогенеза воспалительного процесса в тканях глазной поверхности [1-3] и существенно утяжеляет течение роговично-конъюнктивального ксероза (рис. 1). Вторичная дегидратация эпителиальных клеток роговицы и конъюнктивы (потеря клетками влаги в гиперосмолярную слезную пленку по градиенту ос

The Fas/FasL system is known to play a central role in maintaining peripheral self-tolerance and tissue homeostasis of the organism [12, 18]. Fas-mediated apoptosis is induced by binding of the Fas(CD 95/APO-l/TNFRSF6)-receptor to the Fas(CD 95L/CD 178/TNFSF6)-ligand on the respective cells [24]. Triggering of the expression of cell surface Fas receptors (Fas) regulates the elimination of autoreactive T- and B-lymphocytes by apoptosis. It is known that impaired activation of Fas-mediated apoptosis in individual subpopulations of T-cells plays an important role in the pathogenesis of type 1 diabetes mellitus (T1DM). The main key point in the development of T1DM is resistance to apoptosis of activated autoreactive T-lymphocytes, which migrate from the bloodstream to the pancreas and take an active part in β-cells destruction. Аt the present time, most of the results on the study of Fas-mediated apoptosis in T1DM were obtained in experiments in vitro [11, 18, 31]. There is no doubt that in vivo autoimmune pathological changes are more profound, and extrapolation of the results obtained in the experiment to the organism is not always valid. Тhereby, it seems relevant to evaluate the efficiency of Fas-mediated apoptosis of T-lymphocytes in the blood of patients with T1DM, depending on the compensation phase and the duration of the disease. In the article, the markers of Fas-mediated apoptosis of peripheral blood lymphocytes in patients with type 1 diabetes mellitus and individuals with high risk of T1DM development have been studied. The surface expression of Fas in individual subpopulations of T-lymphocytes was еvaluated. The inhibition of Fas-mediated apoptosis of autoreactive CD 95+-cells by soluble Fas-receptor was detected in patients with decompensation of T1DM. In compensation phase of T1DM Fas-mediated apoptosis of lymphocyte was successfully realized via the soluble Fas ligand (sFasL). The increased level of soluble FasL was revealed in compensation phase of T1DM and in individuals with high risk of T1DM development. This probably has a protective value, since the soluble FasL is involved in the removal of the peripheral blood autoreactive CD 95+-cells.