Patients with 22q11.2 deletion syndrome (DiGeorge syndrome) are characterized by a combination of a wide range of pediatric problems with an immunodeficiency. Defects are characterized by T cell lymphopenia, changes in the functions and subpopulation composition of T and B lymphocytes. Disturbances in lymphocyte homeostasis can lead not only to severe infectious diseases, but also to autoimmune complications, especially in older children. The purpose of this study was to compare the subpopulations of T and B lymphocytes with and without autoimmune complications and to search for prognostic signs that precede the development of complications. The study included 20 patients aged 10 to 18 years with a confirmed diagnosis of DiGeorge syndrome. The patients were divided into 2 groups, according to the presence or absence of autoimmune complications. Subpopulations of lymphocytes were assessed by flow cytometry. No statistically significant differences were found between CD3 T lymphocytes, CD4 T helper, CD8 T cytotoxic and subpopulations of T helper (p > 0.05). However, in the group of patients with autoimmune complications, a statistically significant decrease in CD45RA+ naïve T helper cells was detected, both in relative (p = 0.020) and absolute number (p = 0.025) and regulatory T cells (respectively, p = 0.020 and p = 0.007). Among B-lymphocyte in patients with autoimmune complications, a decrease in memory B cells in relative (p = 0.031) and absolute number (p = 0.005) and switched memory (p = 0.016 and p = 0.031) was detected. But transitional B lymphocytes, on the contrary, were increased in relative quantity (p = 0.003). There were no differences between the groups in the level of plasmablasts, activated B-lymphocytes CD21lowCD38low, IgM only B-cells (p > 0.05). The ROC analysis showed that the most diagnostically and prognostically significant indicators are the relative number of CD45RA+ naive T cells (cut-off ≤ 28.7%), switched memory B cells – relative (cut-off ≤ 5.0%) and the absolute number (cut-off ≤ 11 cells/µL) and the relative number of transitional B cells (cut-off ≥ 12.9%). Our data confirm the important role of regular immunophenotyping and especially subpopulations of CD45RA+ naive T cells, switched memory B cells and transitional B cells in predicting autoimmune complications in this category of patients.

Over a long period of time in Russia we had the lack of the anaphylaxis (AF) register problem as it sounds to be the most important tool for recording, analysis and monitoring of this group of patients. Then, starting 2022, the first “Moscow Pediatric Anaphylaxis Register” has been maintaining at the Morozov Children’s City Clinical Hospital (Moscow, Russia), which systematizes and analyzes all the patient data on the etiology, clinical picture, severity factors and risk of developing AF, which in its turn is undoubtedly extremely valuable for further management of this group of patients. The purpose of this research was to evaluate the severity of AF taking into account the age and gender factors, comorbidity, triggers and clinical symptoms among children among the Moscow agglomeration. Materials and methods used: within the framework of a single-center cohort prospective study, the questionnaire data of 69 pediatric patients aged 0 to 18 y/o, 28 girl/41 boys, who were included in the study in May 2022-Sept. 2023, were subjected to statistical analysis register for emergency hospitalization due to AF. Results: the proportion of patients with severe AF was 30%; two age-related peaks in its frequency were recorded in the groups of children 0 to 3 y/o and 13 to 18 y/o (44% and 35%, respectively). Food triggers were the most significant regardless of the severity of AF; severe food AF was induced by tree nuts in 31%, and cow's milk in 19%. The central nervous and cardiovascular systems in severe AF were involved statistically significantly more often in comparison with the mild/moderate AF groups (86% v 25% and 81% v 30%, respectively, p<0.001), in 63% of cases symptoms developed within 0 to 15 minutes. Statistically significant differences were revealed in the frequency of diagnosis of AF in severe and moderate AF (57% v 12%, p=0.001). Conclusion: severe anaphylactic reactions in children are most often induced by food triggers and are characterized by a high frequency of involvement of the cardiovascular and central nervous systems, rapid development of symptoms, which is extremely important to consider during emergency verification of the diagnosis and immediate administration of epinephrine.

Starting Jan., 2023 the extended neonatal screening (ENS) has been carried out in Russia that includes the determination of TREC/KREС markers, which in its turn allow suspecting severe combined immunodeficiency (SCID), phenotypical T-cell immunodeficiencies and X-linked agammaglobulinemia (XLA) prior to possible development of severe infectious complications. The purpose of the research was to evaluate the results of ENS for congenital immunodeficiency disorders (CIDs) in newborns in Moscow and to subsequently identify the most problematic issues in organizing of its implementation. Materials and methods used: the study was conducted in the Morozov Children's City Clinical Hospital (Moscow, Russia) among the 116,584 children born in Moscow in Jan. 01-Dec. 31, 2023 (this was the first year since the ENS introduction in Moscow) with a decrease in TREC/KREC below 100 copies per 105. Results: a total of 14 patients with CIDs were identified, of which 4 patients had a genetically confirmed form of SCID; 2 patients with immunophenotype of SCID; 3 patients with XLA; 2 patients with DiGeorge syndrome; single patient with a syndrome associated with a mutation in the PI4KA gene; and 2 patients with syndromic pathology without genetic confirmation. Thus, the frequency of detection of patients with the immunophenotype of SCID was a single case per 19,430 children, the frequency of patients with XLA was 1:38,861. 5 of 14 had already received hematopoietic stem cell transplantation, single patient was preparing for it at the time of the manuscript finalization. All of the patients receive regular immunoglobulin replacement therapy. Conclusion: the experience of an integrated approach to the provision of medical care based on neonatal screening in a municipal children's multidisciplinary hospital is presented; the results of the study helped identifying organizational shortcomings and determined the vector for its further development in order to improving of medical care provision to children with CIDs.

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.

Among the wide variety of tree nuts, walnut is an allergen that deserves special attention in the context of acute allergic reactions, due to their severity, low inducing trigger dose, and minimal likelihood of developing tolerance. The overall consumption of walnut has been steadily increasing, while the importance of this allergen as a trigger for anaphylaxis is underestimated due to its often “hidden” presence in foods and the difficulty of trigger verification. This article presents the epidemiological aspects of walnut food allergy, provides current data on the molecular characteristics and properties of various allergen proteins, and their clinical significance for the development of anaphylaxis. The article is supplemented with two clinical cases of food anaphylaxis to walnuts from own clinical practice.

Hereditary angioedema (HAE) is an orphan potentially life-threatening disease characterized by recurrent edema of the skin, mucous/submucosal membranes and is genetically determined. In most cases, there are peripheral edemas and manifestations of marginal erythema at the onset of the disease, much less often - abdominal syndrome. Among patients with HAE, there is a clear predominance of women. In this regard, girls in puberty with primary dysmenorrhea and various menstrual disorders are of particular interest. In the treatment of adolescent girls suffering from these nosologies, combined oral contraceptives (COCs) are often used. The debut of manifestations of HAE in the form of severe abdominal attacks in girls with dysmenorrhea during COC therapy has not yet been described. The article presents descriptions of cases of patients with the outset of HAE in the form of abdominal attacks that developed against the background of treatment of primary dysmenorrhea with COCs. The importance of awareness of pediatricians, pediatric surgeons, gynecologists and doctors of other profiles about this nosology is demonstrated using the examples of these clinical cases’ data.

The aim of this study was to analyze the clinical, laboratory and molecular genetic data of 26 patients (15 boys, 11 girls) diagnosed with mevalonate kinase deficiency syndrome (MKD).Subjects and methods. The age of MKD manifestation ranged from 0 to 30.0 months (M – 1.5 months). Clinical manifestations and their severity were extremely diverse: from symptoms resembling Marshall’s syndrome to severe systemic manifestations with respiratory failure, hepatosplenomegaly and pancytopenia.Results/Conclusion. All patients had homozygous/compound-heterozygous mutations in the MVK gene, including 10 newly described variants. In all 20 patients, who have been treated with IL-1 inhibitors long enough to assess the effect of the treatment, drastic improvement of the condition was noted, but only in 17/20 patients achieved full remission.

According to the data from Russian primary immunodeficiencies (PID) registry 71% of registered patients were treated with immunoglobulins (IG). Regular immunoglobulin substitutions were reported in 90% of patients with primary antibody deficiencies (PAD), 86% - with syndromic PID and 91% of patients with combined T and B cell defects. The study was supported by Academic Council of Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology and approved by Local Ethical Committee within the Russian PID registry. Regular IG substitution was analyzed in the representative cohort of 235 PID patients from 12 Russian regions. Of these 121 were children, 114 – adults. In 78% cases IG treatment has been started during the first 10 years of life. 80% patients were treated with highly safe products (Octagam 5% and 10%, Privigen, IG VENA, Gamunex) reaching therapeutic median pre-infusion level of serum IgG of 7 g/l. Significantly lower levels of pre-infusion serum IgG were observed in patients treated with Gabreglobin-IgG. Irregular treatment was observed in 61% of patients mainly due to the poor drug supply (lack of medication in the health care centers). Infections were reported in 90% percent of patients with irregular treatment. Unscheduled hospitalizations were two times more frequent in the group of patients with irregular IVIG treatment. Additionally, we assessed quality of life of patients with regular IVIG treatment, which significantly improved in comparison with the pretreatment period and became comparable to the group of healthy controls.

According to the data from Russian primary immunodeficiencies (PID) registry 71% of registered patients were treated with immunoglobulins (IG). Regular immunoglobulin substitutions were reported in 90% of patients with primary antibody deficiencies (PAD), 86% - with syndromic PID and 91% of patients with combined T and B cell defects. The study was supported by Academic Council of Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology and approved by Local Ethical Committee within the Russian PID registry. Regular IG substitution was analyzed in the representative cohort of 235 PID patients from 12 Russian regions. Of these 121 were children, 114 – adults. In 78% cases IG treatment has been started during the first 10 years of life. 80% patients were treated with highly safe products (Octagam 5% and 10%, Privigen, IG VENA, Gamunex) reaching therapeutic median pre-infusion level of serum IgG of 7 g/l. Significantly lower levels of pre-infusion serum IgG were observed in patients treated with Gabreglobin-IgG. Irregular treatment was observed in 61% of patients mainly due to the poor drug supply (lack of medication in the health care centers). Infections were reported in 90% percent of patients with irregular treatment. Unscheduled hospitalizations were two times more frequent in the group of patients with irregular IVIG treatment. Additionally, we assessed quality of life of patients with regular IVIG treatment, which significantly improved in comparison with the pretreatment period and became comparable to the group of healthy controls.

The article presents data on the features of COVID-19 infection in patients with primary immunodeficiencies (PIDs) in the Russian Federation, obtained through the National association of experts in PID (NAEPID) registry. Materials and methods: from March 1, 2020 to October 15, 2020, 15 cases of close intrafamilial contact between PIDs patients and COVID-19 patients without reliable infection of the first and 23 cases of COVID-19 infection in PIDs patients were reported. Results: 6/23 infected people had asymptomatic course of infection, 9/23 patients – mild form, 8/23 – moderate form of disease, one patient had a severe course with a fatal outcome. 19/23 patients were under 18 years of age, which corresponds with the age data of the national Russia PID registry. Conclusion: perhaps this age composition partially explains the milder course of COVID-19 in PIDs patients compared to the European data. Other possible reasons for a milder course may be the lower pathogenicity of the coronavirus strain circulating in the Russian Federation.

Hyper-IgD syndrome, one of the forms of mevalonate kinase deficiency (MKD), is a rare autosomal recessive disorder caused by mutation in the MVK gene. The disease usually starts in early age. The most specific clinical manifestation includes recurrent episodes of fever, abdominal pain, diarrhea, vomiting, arthralgia, and lymphadenopathy. However, not all patients present with the typical clinical features of MKD. A retrospective analysis of clinical manifestations and results of therapy of 6 children (4 girls, 2 boys) with MKD is carried out. The first symptoms of the disease manifested during the first 6 months of life in all the patients. All patients suffered from periodical fever, lymphadenopathy (mainly the cervical nodes were involved), abdominal pain, nausea/vomiting. Five patients had diarrhea, sometimes with blood, and one patient suffered from chronic constipation. Rash was observed in 4 patients, myalgia and arthralgia in 4, aphthous stomatitis in 5, and neurological symptoms in 2 patients. One patient developed periorbital edema and eyelid hyperemia during an attack: these symptoms were not described previously. One patient died under conditions of macrophage activation syndrome and amyloidosis. Four of six patients received interleukin-1 inhibitors (anakinra and/or canakinumab), which led to clinical and laboratory remission.

This specific clinical example of a female patient with DiGeorge syndrome, a primary immunodeficiency disease, demonstrates difficulties in its timely diagnosis and in the choice of treatment policy in this category of patients. Lung injury in them is frequently the only manifestation of the underlying disease. Special attention is given to current diagnostic criteria (including genetic ones) and approaches to treatment and prognosis in patients with DiGeorge syndrome.

Hyper-IgD syndrome, one of the forms of mevalonate kinase deficiency (MKD), is a rare autosomal recessive disorder caused by mutation in the MVK gene. The disease usually starts in early age. The most specific clinical manifestation includes recurrent episodes of fever, abdominal pain, diarrhea, vomiting, arthralgia, and lymphadenopathy. However, not all patients present with the typical clinical features of MKD. A retrospective analysis of clinical manifestations and results of therapy of 6 children (4 girls, 2 boys) with MKD is carried out. The first symptoms of the disease manifested during the first 6 months of life in all the patients. All patients suffered from periodical fever, lymphadenopathy (mainly the cervical nodes were involved), abdominal pain, nausea/vomiting. Five patients had diarrhea, sometimes with blood, and one patient suffered from chronic constipation. Rash was observed in 4 patients, myalgia and arthralgia in 4, aphthous stomatitis in 5, and neurological symptoms in 2 patients. One patient developed periorbital edema and eyelid hyperemia during an attack: these symptoms were not described previously. One patient died under conditions of macrophage activation syndrome and amyloidosis. Four of six patients received interleukin-1 inhibitors (anakinra and/or canakinumab), which led to clinical and laboratory remission.