A.P. Prodeus, N.D. Odinayeva, S.V. Voronin, I.N. Zakharova, I.A. Tuzankina, N.N. Volodin, K.V. Zhdanov, A.N. Pampura, D.I. Sadykova, E.I. Kondratyeva, A.A. Korsunskiy, E.A. Degtyareva, K.V. Savostyanov, S.A. Trusova, A.Yu. Lobenskaya, Ye.S. Nikonova, A.S. Lebedeva, E.V. Loshkova, V.D. Denisova, A.G. Rumyantsev. Guidelines for routing, monitoring and management tactics of immunocompromised children at risk and patients with congenital immune defects. Pediatria n.a. G.N. Speransky. 2024; 103 (6): 218-245. DOI: 10.24110/0031-403X-2024-103-6-218-245. [Reviewed by Drs. O.V. Zaytseva, N.I. Zakharova and O.V. Kalyuzhin. Approved as official Guidelines for Practitioners by the Educational and Methodological Commission of the Research and Clinical Institute of Childhood with the Moscow Oblast Healthcare Ministry (Mytishchi, Moscow Oblast, Russia), Record No. 8 dated Nov. 11, 2024]

Incidence of infectious complications in children with congenital heart disease, especially with cyanotic and complex defects, is higher than in the population, which is associated with both hemodynamic and immune disorders. Various types of primary immunodeficiencies in congenital heart disease and the dependence of immune disorders on the morphology of the defect, the severity of circulatory failure and arterial hypoxemia are described. The importance of diagnosing immunological disorders is emphasized to reduce the risk of infectious complications of cardiac surgery, reduce mortality and improve the outcomes of surgical interventions for congenital heart disease. The prognostic value of immune disorders identified by the TREC/KREC method for infectious complications of cardiac surgery has not been studied. The purpose of this research was to assess the possibility of predicting infectious complications of cardiac surgery in children with congenital heart disease based on screening using the TREC/KREC method. Material and methods used: preoperatively, 200 children with congenital heart disease aged 3 days to 12 months old were examined. Instrumental and laboratory methods were used including immunological screening for TREC/KREC DNA. Results: 123 (62.4%) were diagnosed with “acyanotic” congenital heart disease, 74 (37.5%) with various cyanotic congenital heart diseases and 10 (5%) with congenital heart diseases with Down syndrome, Di George syndrome, Williams syndrome or multiple malformations. 184 (92%) underwent various cardiac surgical interventions. Violations of T-cell immunity according to preoperative TREC/KREC screening were observed in 23.5% of cases including in all children with syndromic forms of congenital heart disease, multiple malformations, and significantly more often in cyanotic congenital heart disease, conotruncal defects, and those admitted in critical conditions. Infectious complications of cardiac surgery were observed significantly more often in this group than in children with normal T-cell immunity (in 36% and 3.6%, respectively). Conclusion: the prognostic value of TREC/KREC screening for targeted preparation and postoperative management in order to prevent infectious complications of cardiac surgery has been confirmed.

In September 2024, an Expert Council via videoconference was held to discuss innovative approaches to the tactics of diagnosis and therapy of influenza in children and adolescents in Russian Federation.Influenza is characterized by high morbidity and mortality, leading to 28,000 deaths annually worldwide among children.Influenza causes significant economic damage, ranking 4th among all infectious diseases in 2023 in Russian Federation. During the 2022­2023 period, there was an increase in influenza incidence with a traditionally high rate of infection among children. Newborns, children under 5 years old, and children with comorbidities are at high risk for complications. An analysis of influenza mortality shows that comorbidity is an aggravating factor in almost half of the cases.Timely diagnosis and etiotropic therapy are key in the treatment of influenza. The focus should be on etiological confirmation of the diagnosis within the first 24 hours from disease manifestation to prescribe specific antiviral therapy. Although laboratory confirmation of the diagnosis is recommended, during periods of high incidence, the diagnosis can be made based on clinical and epidemiological data. For final verification of the “influenza” diagnosis, the widespread use of certified rapid tests is proposed.According to the updated WHO guidelines published in September 2024, two medicines are recommended for the treatment of influenza — baloxavir and oseltamivir. Baloxavir marboxil significantly reduces the virus shedding time and has a favorable safety profile for children and adolescents. This makes it the medicine of choice, especially in cases of high risk of complicated influenza infection.Given the high importance of influenza in the structure of childhood morbidity, it is crucial to continue improving methods of prevention, diagnosis, and treatment of this disease, especially in children.

Patients with the 22q11.2 deletion syndrome (DiGeorge syndrome, DDS) suffer from T-cell lymphopenia, changes in function and subpopulation of T-lymphocytes. The bibliographical data conflicts on the characteristics of T-lymphocytes in patients with DDS and their changes during physiological maturation. The purpose of this research was to follow-up patients with emphasis on the dynamics of changes in T-lymphocyte subpopulations with age. Methods used: 117 patients observed during 2013-2023 who were administered at the Allergology and Immunology Department with the G.N. Speransky City Children’s Hospital No. 9 (Moscow, Russia) with a diagnosis of DDS and who had undergone blood sampling to assess T-lymphocyte subpopulations using flow cytometry. All patients (0 to 18 y/o) were divided into 4 age groups: 0 to 2 y/o, 2 to 5 y/o, 5 to 10 y/o and 10 to 18 y/o. In parallel, the blood samples of 185 apparently healthy children of the corresponding age were examined. Results: a decrease in CD3 T-lymphocytes, CD4 T-helper cells, CD8 T-cytotoxic lymphocytes, CD4 early thymic emigrants and CD4 naive T-lymphocytes was found in all age groups (p<0.05). CD8+ naive T-lymphocytes and CD8+ early thymic emigrants were reduced in all age groups, but in the 2 to 5 y/o age group their values were close to normal (p=0.072 and p=0.220, respectively). CD4+ central memory cells were elevated in all age groups (p<0.001), while CD8+ central memory cells, CD4+ and CD8+ effector memory cells differed in that they had normal values in the 2 to 5 y/o age group (p=0.229, p=0.457 and p=0.140, respectively). CD4+ TEMRA were significantly increased in the 0 to 2 y/o age group (p=0.002), and in older age groups they tended to normal values. CD8+ TEMRA did not differ from the control group and did not have age-related dynamics. The T-helper subpopulations were characterized by a significant increase in the percentage of T-helper type 1, T-helper 17, T-helper 17.1 and a decrease in T-helper type 2 compared to the population of healthy blood sample donors (p=0.001), except for patients from the 2 to 5 y/o age group. T-regulatory cells in absolute amount were reduced in all age groups (p<0.001), while their relative number corresponded to the norm in the 0 to 2 y/o age group (p=0.811) and decreased slightly in patients in older age groups, especially in the 2 to 5 y/o age group (p=0.030). Conclusion: the pathology of thymus development in patients with DDS leads to impaired maturation of T-lymphocytes, leading to an increase in the number of mature forms of T-lymphocytes, shifts towards the development of T-helper 1 and T-helper 17, and a decrease in T-regulatory cells. Disturbances in T-lymphocytes can cause changes (dysregulation) in subpopulations of B-cells. All these processes may underlie the progression of autoimmune and infectious complications in such patients that are increasing with aging.

The prevalence of allergic diseases in the population varies in different countries from 10 to 40%. Improving the quality of diagnosis, treatment and prevention of allergic diseases is an urgent public health problem. The article deals with the etiology, pathogenesis, clinical picture and diagnosis of allergic diseases. The main stages of allergy diagnosis include a number of specific and non-specific examination methods. In particular, the authors consider various methods of laboratory diagnostics, discuss the indications and contraindications, and the benefits and drawbacks of various diagnostic methods. Although skin testing conducted by an allergist is the gold standard for the diagnosis of allergies, it has several contraindications and limitations, in the presence of which it is possible to perform laboratory diagnostic methods in vitro. For laboratory tests, it is necessary to choose a laboratory that uses modern methods of the third generation with an accuracy of 0.1 kU/L to detect allergic reactions, starting with the first class of significance. However, despite the importance of laboratory diagnostic methods, the conclusion should be made only after comparing with the following: clinical picture, data of the allergic, pharmacolo gical and food history, results of instrumental studies and skin tests (in t he absence of contraindications to their use). KEYWORDS: atopy, allergy, laboratory diagnostics, immunochemiluminescence assay, skin test, atopic dermatitis, allergic rhinitis, bronchial asthma, dermato-pulmonary syndrome. FOR CITATION: Rybnikova E.A., Prodeus A.P., Fedoskova T.G. Modern laboratory diagnostic methods of allergy to help the practicing physician. Russian Medical Inquiry. 2021;5(1):43–49. DOI: 10.32364/2587-6821-2021-5-1-43-49.

Objective. To evaluate the composition of intestinal microbiota in children with atopic dermatitis (AD) aged 1–5 years depending on the disease severity. Patients and methods. We have examined 60 children aged between 1 and 5 years diagnosed with AD. In outpatient settings, they have undergone comprehensive clinical and laboratory examination that included analysis of patient's medical history, physical examination, assessment of clinical status using the SCORAD scale, complete blood count, urinalysis, analysis of feces, liver function tests, measurement of total IgE and specific IgE, and bacteriological analysis of feces. The composition of intestinal microbiota was assessed using bacterial 16S rRNA gene sequencing with subsequent bioinformatic and statistical analysis. Results. The analysis of intestinal microbiota in 60 AD children aged 1–5 years using 16S rRNA sequencing demonstrated an association between the composition of intestinal microflora and disease severity. Both bacterial count and species diversity directly depend on the disease course. Children with complicated AD had a very poor diversity of intestinal microorganisms compared to those in remission (р ≤ 0.002). Children with signs of AD exacerbation demonstrated an increased count of Actinobacteria species (р = 0.018) and a decreased count of Proteobacteria species compared to children without clinical manifestations of AD (р = 0.033). We also observed a decrease in the amount of bacteria belonging to Oscillospiraceae and Erysipelatoclostridiaceae families (р = 0.03 : 0.034) in children with AD exacerbation and children with signs of secondary infection. Patients with acute disease and patients with signs of secondary infection were also more likely to have lower level of Bifidobacterium longum (р = 0.03 : 0.034) than patients in remission. Conclusion. Our findings suggest that the intestinal microbiota of children in remission differs from that in children with AD exacerbation or complicated AD. The composition of commensal flora, as well as species richness directly depend on the disease severity. Children with AD exacerbation were found to have lower concentration of Oscillospiraceae species and B. longum that are crucial for normal functioning of the gastrointestinal tract and modulation of the immune response. Understanding of the metabolic potential of bacteria will enable adequate diet correction of the intestinal microbiota. Thus, sequencing of bacterial 16S rRNA genes is very helpful in the diagnosis of AD. It also opens new horizons in the search for new treatment methods. Key words: alpha diversity, atopic dermatitis, children, intestinal microbiota, molecular genetic methods, 16S sequencing

Воспалениедруг или враг?1 Федеральное государственное бюджетное учреждение «Государственный научный центр «Институт иммунологии» Федерального медико-биологического агентства

В монографии обобщены современные данные о диагностике и лечении нарушений функции иммунной системы при инфекционных болезнях. Освещены основные вопросы этиологии, иммунопатогенеза по основным нозологиям. Описаны методы клинической и лабораторной диагностики иммунных нарушений. Особое внимание уделено разделу иммунотерапии в клинике инфекционных болезней и современным методам коррекции иммунных нарушений. Книга может представлять интерес для инфекционистов, но может представлять интерес для широкого круга практикующих врачей различных специальностей, работающих в лечебных учреждениях амбулаторно-поликлинического звена

The clinical manifestations of immunodeficiency states (IDS), whether primary or secondary, are extremely nonspecific. The consequence of this is the belated setting of the correct diagnosis and, accordingly, the late start of the necessary therapy. Early detection of IDS is a key factor in the successful treatment of patients with these diseases. Determination of the concentration of TREC and KREC in whole blood and dry blood stains by real-time PCR has already proven its effectiveness for newborns and children in the first year of life. Objective of the study: to determine the concentration reference values of TREC and KREC in peripheral blood and dry spots in children and adolescents aged 1–17 years. Materials and methods of research: 162 conditionally healthy individuals were examined, including 64 at the age of 1–5 years, 47 – 6–11 years old and 51 – 12–17 years old. The concentration of TREC and KREC DNA in peripheral whole blood and dry blood spots on neonatal screening cards was assessed by PCR. Results: reference intervals and threshold values of TREC and KREC content in dry spots and in peripheral whole blood of children and adolescents aged 1–17 years were built and substantiated. Conclusion: the obtained reference values are very convenient for identifying patients with T- and/or B-cell lymphopenia, as well as monitoring the number of naive T- and B-lymphocytes in the peripheral blood of patients with already known diseases in wide pediatric practice.

A review of the accumulated data on the use of glucosaminylmuramyldipeptide (GMDP, Likopid drug) and the assessment of its effectiveness in children are presented. Objective of the research: to systematize the results of clinical trials of the efficacy and safety of GMDP therapy in neonatology and pediatrics. Materials and methods. Publications were searched for in Pubmed/MEDLINE, ScienceDirect, Cochrane, Elibrary.ru, registers of clinical trials and in open sources on the Internet. The authors assessed the level of evidence for reliability and the methodological quality of the studies. Results. The screening resulted in selection of 38 clinical trials with satisfactory methodological quality and a total of 2,692 0-18 year old patients. The effectiveness of use of GMDP (Likopid) as part of complex therapy for infectious diseases of the respiratory tract (2A), allergy-related diseases (2A), herpesvirus infection (3B), dysbiosis/dysbacteriosis (3B), and newborn respiratory distress syndrome (2B) has been demonstrated. The safety assessment is given in 7 studies, of which 5 confirmed absence of any adverse events. Scope of application. The results of the review enable practitioners to prescribe GMDP (Likopid) based on the levels of evidence. The existence of evidence base for the use of GMDP in newborns allows us to raise the question of restoring appropriate indications in the Instructions for Medical Use. Conclusions. For a number of nosologies, further studies of modern design, based on the principles of evidence-based medicine, are required to assess the efficacy and safety of GMDP for good clinical practice in neonatology and pediatrics.

In this work, we used a reference population of newborns and sampled dried blood spots on Guthrie cards of 2,739 individual samples to determine the reference intervals for TRECs and KRECs values, in order to diagnose primary immunodeficiency by means of neonatal screening. The median absolute values for TRECs and KRECs were 195 (CI95%: 185-206) and 185 (CI95%: 176-197) copies per μl, respectively; the normalized value for TRECs was 2780 (CI95%: 2690-2840), and for KRECs, 2790 (CI95%: 2700-2900) copies per 2 × 105copies of the albumin gene or 105cells. The reference interval was calculated for 99 and 99.9 percentiles of total TRECs and KRECs individual values. Due to asymmetric distribution of data, the outliers were filtered off, using the Tukey’s criterion applied after logarithmic transformation of the data. When analyzing absolute values for TREC/KREC (per μL of blood), no “drop-down” TRECs values were identified; for KRECs, 18 experimental values were excluded from further analysis (from 9.8 to 13.5). The outlying values were not identified among the normalized values of TRECs/KRECs. The obtained reference values for TRECs and KRECs (at the 0.1 percentile level) were, respectively, 458 and 32 per 105cells, or 23 and 17 per μl of blood samples from neonates.

Microbiocenosis of various ecological niches of the human body has been studied for many years around the world. In this article, gut microbiota is considered as a separate system of the human body. The relevance of this issue is due to importance of microbiota for the human body. Gut microflora performs various essential functions: participates in digestion, vitamins, hormones and biologically active substances synthesis. Microbiota influences our health, immune response against various adverse factors and formation of the primary prevention of diseases starting from infancy. Human microbiome is a large community of bacteria, viruses and fungi. Development of molecular and genetic testing expanded our knowledge about taxonomic composition of microbiomes and their role and functions in the human body. Undoubtedly, bowel has the most diverse spectrum of microorganisms that needs further investigation. Moreover, modern advances in medical science make it possible to consider gut microbiotope as a new organ or system of the body with its typical features: integrity and divisibility, stable connections, organization and emergence. The purpose of this review is to prove that gut microbiota is a separate functioning system of the human body.