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Type I allergy is mediated by the formation of IgE antibodies to proteins secreted by nonreplicating microorganisms (plant pollen, house dust mites, etc.) that enter the mucous membranes in very low concentrations. The mechanisms and localization of naive B cells’ switching to IgE production have not been fully determined. The aim of this work was to determine the switching site of B cells and the traffic of IgEproducing B cells in mice immunized with a low dose of equimolar mixture of egg proteins Gal d1, Gal d2, and Gal d3. Allergens in saline solution were injected into the withers of mice 9-10 times with an interval of 2-3 days; the total dose was 2.7 µg/mouse. The production of IgE to Gal d proteins in the blood and by B cells isolated from the withers, draining lymph nodes, spleen, and bone marrow of immune mice was analyzed in dynamics after cessation of sensitization. Both in blood and in in vitro cultures, the dominance of IgE changed from the recognition of the LMW Gal d2 during the sensitization of mice to the HMW Gal d3 after sensitization was discontinued. In this model, an IgG memory response appeared only a month after the end of sensitization and recognized only Gal d3. In vitro cultures showed that B cells switched to IgE production locally in the withers with low traffic to the spleen. In the blood serum, IgE titers for all Gal d proteins decreased after the cessation of sensitization and persisted for a long time. A month after the cancellation of the sensitization, a pool of B cells producing IgE in vitro appeared in the spleen. These B-cells died after 20-30 days as no in vitro IgE production was observed later than 85-90 days. The results obtained allowed us to draw several conclusions. B cells switch to IgE synthesis locally at the site of allergen injections. The response was two-phase: LMW Gal d2 was recognized in the early response, while HMW Gal d3 was recognized in the late phase. In this model, the IgG response to HMW Gal d3 was clearly dominant. In conclusion, it has been shown that when the immune system recognizes a mixture of proteins originating from some allergen, the dominance of proteins recognized by both IgE and IgG is observed. Since allergy patients most often do not have IgG antibodies, it can be assumed that in this case an acute phase response, supported by antigen intake, is observed, in which LMW allergens are recognized.

In pediatric practice, epilepsy holds one of the leading places among neurological pathologies. Along with seizures, a child's intellectual impairment lowering quality of life plays a crucial role in social disintegration. Cognitive impairments occuring in idiopathic generalized epilepsies (IGE) and self-limited epilepsy with centrotemporal spikes (SeLECTS) considered benign have been widely investigated. However, available data suggest that such disorders result in multiple persistent alterations in the cognitive sphere. In this case, features of the epilepsy etiopathogenesis account for disease early onset and profoundly remodeled structures involved in the implementation of cognitive functions. Current review is aimed to summarizing data regarding developmental mechanisms and range of cognitive impairment in IGE and SeLECTS.

The main mechanism for the occurrence of urticaria is the degranulation of mast cells. It has been proven that, regardless of the activation pathway, clinical manifestations will not differ. According to the literature, up to half of cases of chronic spontaneous urticaria are autoimmune in nature, can be combined with autoimmune thyroid disease, SLE, etc., and have a more severe course.In therapy, antihistamines are traditionally used. However, some patients do not respond to the treatment, even with a multiple increase in doses. In the treatment of urticaria resistant to traditional antihistamines, the use of Omalizumab is recommended. The purpose of the study: to determine the profile of patients with chronic urticaria, as well as to evaluate the effectiveness of treatment with Omalizumab in patients with IgE- dependent and IgE-independent chronic urticaria.Eight-one patients with chronic urticaria (60 adults, 21 children) were examined. Patients before the start of therapy had a long history of CU: from 1 to 20 years. Patients before the start of therapy were treated with antihistamines, but no control was obtained. An increase in the level of serum IgE was detected in 51.7% of cases in adults and 42% in children. Concomitant sensitization was determined in 48.3% of adults and 76.2% of children. In children, food, epidermal and pollen sensitization was the most common. Pollen and epidermal sensitization were more common in adults. The level of eosinophilia in the group with IgE-dependent was more pronounced than in other group (p = 0.0097). After 6 months, the group with IgE-dependent showed an improvement in the symptom score (UCT) from 3.1 CI (1.5-4.6) to 12.2 CI (10.8-13.7), (p = 0.0001). In other group, symptoms improved from 0.63 CI (0.36-1.6) to 8.1 CI (5-11.2) after 6 months (no control). After 6 months of genetically engineered biological therapy (GIBT), complete control over the symptoms of CU in group 1 was obtained in 66.7% of patients, partial — in 33.7%. In the second group, in 33.3% of cases, positive treatment results could not be achieved. Thus, genetically engineered biological therapy with Omalizumab increases the control over the course of CU. Treatment outcomes are higher in patients with an IgE-dependent disease profile.

И аллергические, и онкологические заболевания представляют собой две глобальные проблемы современной медицины, далекие от своего решения. Обе патологии являются иммуноопосредованными, но в случае аллергии имеет место гиперчувствительность вследствие срыва иммунной толерантности, а в случае онкологии заболевание развивается именно из-за иммунной недостаточности, связанной с избыточной толерантностью. Ключевым фактором роста злокачественной опухоли является формирование максимально «дружественной» среды со стороны ее микроокружения. Различные компоненты иммунитета, теоретически, должны эффективно распознавать и уничтожать клетки опухоли еще на начальных этапах ее развития, до образования клинически значимого опухолевого роста. Однако клинические исследования говорят об обратном. Различные компоненты иммунной системы (опухоль-ассоциированные макрофаги, цитокины — факторы роста, супрессорные клетки миелоидного происхождения) участвуют в патогенезе опухолевого роста, не противодействуя, а способствуя развитию новообразования, его инвазии и метастазированию. И поэтому одной из основных целей в области лечения онкологических заболеваний является разработка вмешательств, которые могут нарушить иммунологическую толерантность и остановить прогрессирование рака. Многочисленные эпидемиологические исследования предполагают обратную ассоциацию между аллергическими заболеваниями и развитием злокачественных новообразований. Немало также доказательств концепции способности клеток иммунной системы и IgE разрушать опухолевые клетки. Проводятся многочисленные исследования in vitro, которые «нацеливают» данный класс антител на соответствующие опухолевые антигены. Было продемонстрировано, что антитела класса IgE специфичны для сверхэкспрессированной опухоли, они превосходили любой другой класс иммуноглобулинов в отношении антителозависимой клеточной цитотоксичности (ADCC — antibody-dependent cell-mediated cytotoxicity) и фагоцитоза (ADCP — antibody-dependent cell-mediated phagocytosis). И поэтому эозинофилы, тучные клетки и макрофаги в совокупности с IgE могут стать мощными противоопухолевыми эффекторами. Специфичный к опухолевым антигенам IgE вызывает эозинофил-опосредованную гибель опухолевых клеток цитотоксическими механизмами. Характер влияния тучных клеток на опухоль определяется комплексом факторов. Установлено, что в зависимости от своей локализации по отношению к опухоли тучные клетки могут демонстрировать разнонаправленные эффекты. Неоднозначные свойства клеток иммунной системы, синтезируемых ими медиаторов и различных классов иммуноглобулинов привлекают внимание исследователей всего мира. Было установлено, что между наличием у пациента аллергии и риском развития некоторых видов рака (глиома, рак поджелудочной железы и детский лейкоз) прослеживается обратная зависимость. Данные проспективных исследований подтвердили также негативную ассоциацию аллергии с колоректальным раком.

In view of increased incidence of IgE-mediated diseases in Russia and worldwide, the efforts of various research groups are focused on studying the mechanisms that trigger the process of switching B-lymphocytes to IgE synthesis upon human exposure to harmless allergens, including the role of various antigen-presenting cells (APCs) in this process. However, the role of distinct APCs upon long-term penetration of low antigen doses via the tissue barriers, is yet poorly understood, as well as specific features of these events upon entrance of the antigen through the subcutaneous adipose tissue which contains tissueassociated lymphoid clusters (TALC).The aim of this work was to determine the relationship between the local accumulation of various APCs in the subcutaneous adipose tissue and development of early IgE production in a clinically relevant experimental model of allergy with long-term administration of low allergen doses. In this experimental model, specific IgE synthesis is induced, with minimal concomitant IgG production, thus mimicking the situation observed in patients with clinically sound allergies. BALB/c mice were immunized for 4 weeks subcutaneously in the withers area or intraperitoneally with low (100 ng) or high (10 μg) doses of the model allergen (ovalbumin). Blood samples were taken weekly from mice for ELISA testing, to determine the production of specific antibodies. Provocation tests were performed with high dose of the allergen, and adipose tissue samples were taken from the site of antigen injection for flow cytometric assays, in order to evaluate the contents of various APC subpopulations. Specific IgE production was induced mainly by subcutaneous injection of the antigen at low doses (100 ng) into the area of withers. When using this experimental regimen, we observed accumulation of classical CD11b+ cells in adipose tissue at the withers site, but not in the peritoneal adipose tissue, in absence of CD11b- classical, inflammatory or plasmacytoid, dendritic cells. These findings coincided in time with increased production of specific IgE on days +14 to +21. Accumulation of CD11b+CD11c- macrophages and their CD206+ M2 subpopulations at early terms (days +7 and +21) was also observed only after subcutaneous injection of the antigen into the withers area. The high-dose antigen injection (10 μg) which mediated IgG1 production to greater extent than production of IgE, led to earlier accumulation of CD11b+ classical dendritic cells (on day 7th), and to the absence of macrophage accumulation at later stages (day 21th). Thus, the early start of specific IgE production upon low-dose injection of the antigen into the subcutaneous adipose tissue may be associated with its presentation by CD11b+ classical dendritic cells in the presence of CD11b+CD11c- macrophages.

The objective: to study the level of serum cytokines IL-4, IFN-γ and the activity of IgE production in patients with bronchial asthma (BA) with the consideration of the Gln27Glu-polymorphism of the β2-AR gene.Subjects and Methods. 130 people of Uzbek ethnicity were examined including 83 patients with BA. BA patients were divided into groups according to the international classification of the World Health Organization and the GINA 2006 diagnostic criteria. Genotyping was performed by polymerase chain reaction technology and restriction fragment analysis.Results. In the group with allergic BA, patients with the Gln27Gln-polymorphic variant of the β2-adrenergic receptor gene had an average IgE value (1,664.20 ± 293.29 pg/ml) higher versus patients with the Gln27Glu genotype (338.40 ± 121.33 pg/ml; p < 0.01). No significant relationship between the Gln27Glu polymorphism of the β2-adrenergic receptor gene and the activity of inductor cytokines was found. The Gln27Gln genotype of the β2-adrenergic receptor gene in patients with bronchial asthma, especially in the allergic form of the disease, is associated with hyperproduction of IgE.

The incidence of infectious allergy has been growing mainly due to infection with Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, with enhancing allergic background by yeast-like fungi of the genus Candida. The frequency of infection has currently become a threat without tending to decline. Undoubtedly, Staphylococcus aureus is a pathogenic species producing highly powerful exotoxins exerting properties of cytolysin capable of disrupting the integrity of any cell wall, destroying epithelial cells, damaging mucous membranes in any organ, including the intestines, wherein it becomes accumulated at any location of staphylococcal inflammation. At the same time, almost 90% of cases of allergic reactions are diagnosed with atopic dermatitis because IgE level in some cases of infectious allergy is increased. The mechanism of the pathogenetic action of reagins is realized by re-binding of antigens to IgE fixed on mast cell and basophil surface resulting in FcR1 cross-linking and release of vasoactive mediators responsible for developing early phase of allergy. IgE concentrations, accounting for only 0.002% of the total blood immunoglobulins in an apparently healthy person, may remain low in atopic bronchial asthma, atopic dermatitis, allergic rhinoconjunctivitis, etc. IgE level is increased not only in atopy, but also in oncopathology, autoimmune diseases, whole body cooling and IgA deficiency. In allergic reactions, an increased level in the extracellular pool of various receptor structures is recorded. Of interest is a comparative analysis of the ratio between frequency of IgE reactions and CD23 shedding in infectious allergies of various etiology. The aim of the study is to establish a role of the CD23 extracellular pool in pathogenetic mechanisms of infectious allergy. There were examined 678 subjects who were at apparently healthy state at the time of the examination, including 545 females and 133 males, as well as 1481 patients with verified infectious allergy who live in the Arkhangelsk Region. It has been established that patients with staphylococcal infection had markedly aggravated symptom complex of pathological reactions linked to anemia, neutropenia and deficiency of phagocytic protection. Pathological reactions in infectious allergies are accompanied by sharply increased level of sCD23 with its abnormally high concentrations ( 200 ng/ml) found in 51.7% of cases paralleled by increased level of serum IL-10 and reagins in 21.43 and 35.7% cases, respectively, along with phagocytic defense deficit observed in 85.7% as well as accumulation of CEC in 92.86%. A parallel increase in level of sCD23 and IgE is associated with increased percentage of T helpers, cytotoxic T lymphocytes, activated T cells expressing IL-2 receptor, along with upregulated of the MHC II molecules.

Clinical and molecular heterogeneity of bronchial asthma has been documented in recent years. The search for novel solutions to enhance efficient patient support related first of all to understanding of asthma heterogenic nature and allows to personalize each patient treatment. Biological therapy application can influence to achieve better control at greater extent for patients with severe uncontrolled asthma. Nowadays 5 biological drugs are registered on Russian Federation territory and implemented according to severe asthma phenotypes: anti-IgE, anti-IL-4,13 and anti-IL-5 class therapies. Omalizumab become the first target drug for uncontrolled allergic asthma patients (monoclonal antibody against IgE). This medication is prescribed for uncontrolled moderate and severe allergic (atopic) asthma in patients on basic asthma therapy according GINA step 4 and 5 (Level of evidence A). Clinical trials confidently reported that anti- IgE-therapy reduces the rate of asthma exacerbations, severity of disease in patients with chronic severe asthma on high doses of inhaled steroids or systemic steroids and allows to reduce or withdraw systemic steroids doses in case of steroid-dependent asthma. For the last years special attention led to and demonstrated omalizumab positive effect on airways remodeling and modification of bronchial asthma natural course in adults and children. Antiinflammatory effect of omalizumab is documented. Omalizumab significantly reduces eosinophilic infiltration of submucosal bronchi layer among patients with atopic asthma, sputum eosinophilia, which correlates with reduction of FeNO during biologic treatment, reduces mast cells infiltration of smooth muscle cells in bronchi. Omalizumab significantly reduces the thickness of the bronchial wall, increases the lumen of the bronchi (positive dynamics of CT-scan parameters), which is clinically manifested by increased of FEV1.

A search for prognostic markers of HIV and tuberculosis coinfection (HIV/TB), especially in case of Mycobacterium tuberculosis multidrug resistance (MDR MBT) associated with low rates of TB eradication, is of relevance in connection with the problem of choosing adequate anti-TB therapy which is able to decrease mortality. 113 HIV/TB patients aged 24 to 58 years were examined: 70 males and 43 females hospitalized at the Novokuznetsk TB Clinic during the 2017—2019 period. MDR MBT (concomitant resistance to Isoniazid and Rifampicin) was found in 50 patients (12 patients with MDR MBT had additional resistance to Fluoroquinolones) aged 24 to 54 years — 31 males and 19 females. The control group consisted of 49 healthy individuals aged 27 to 72 years (26 females and 23 males) lacking focal and systemic infections with moderately pronounced age-related changes. In plasma samples, concentration of total (non-specific) immunoglobulins of classes E, M, G, A (including secretory immunoglobulin A, sIgA) were measured by using enzyme-linked immunosorbent assay. Data statistical processing was performed by using licensed software packages InStatII, Microsoft Excel, IBM SPSS Statistics 22. An extended range of individual variability in count of peripheral blood CD4 lymphocytes was revealed both among non-survivor and survivor patients with HIV/TB examined, being a drawback of using such parameter as lethality predictor. It was found that the serum level of total IgE, IgM, IgG, IgA and sIgA in patients with HIV/ TB was higher than that one in control group, whereas in non-survivor vs. survivor patients the concentration of IgE and sIgA was elevated. The coefficient of disease outcome prediction (CP) for patients with HIV/TB and MDR MBT was calculated being equal to the ratio of the multiplication of serum concentration of IgE, IgM, IgA and secretory IgA to CD4 lymphocyte count (CP = IgE x IgM x IgA x sIgA/CD4). CP higher than 200 was detected in 77% non-survivor and 6% of survivor patients. The relative risk of death with CP > 200 was very high (OR = 56.7, p < 0.0001) being 8.5 times higher than that one upon CD4 < 200 (OR = 6.7, p = 0.0237). A positive correlation between CP and lethal outcome was more valuable than that of CD4. The data presented allow us to propose CP for clinical use as an effective prognostic criterion for HIV/TB with MDR MBT.

Diagnostics of allergic diseases is a difficult issue, which requires distinct solutions, since this disorder is very common among the population. The overview focuses on complex diagnostics, including various methods that are most in demand at the present stage. The allergy diagnostics primarily include taking anamnesis, physical examination, instrumental and functional tests. Less often, the provocative tests are used, due to risk of severe adverse reactions. At the present stage, the role of laboratory diagnostics of allergies is growing, since, firstly, there is an increase in difficult-to-diagnose cases that require involvement of the entire medical armamentarium, and, secondly, the sensitivity and specificity of laboratory tests are improving. Among laboratory methods, the most significant are the assessment of the level of specific IgE, and the relatively new basophile activation test. The latter test is the main focus of the present review. It is functional and combines the advantages of provocative tests, during which conditions are created for the interaction of a potential allergen and effector cells of allergic inflammation, keeping safety for the patient. The data on the life cycle of basophils, their expression of membrane receptors, the content of granules, and ability to produce additional inflammatory mediators by the cells are presented. Participation of these cells in pathogenesis of allergic inflammation is being considered. Various mechanisms of basophil activation are discussed, both IgE-mediated and IgE-independent, which are similar in vivo and in vitro. Theoretical aspects of using the in vitro basophil activation test to estimate the hypersensitivity to a wide range of allergens are discussed. High sensitivity and specificity of the test for diagnosing allergies to food, household, pollen, insect and drug allergens are presented. Specific features of the basophil activation test related to the preanalytical, analytical and postanalytical stages of the study are highlighted. The factors influencing evaluation of this method are known. For example, difficulties in interpreting the test may arise while taking glucocorticosteroid hormones, in acute period of inflammation, with severe edema. The possibility of using this test to assess effectiveness of allergen-specific and anti-IgE therapy is being considered. A comparison of the basophil activation test, measurement of specific IgE and skin tests by various parameters related to performance and interpretation of results is carried out. Comprehensive diagnostics of allergic diseases, including usage of pathogenetically determined laboratory methods, will contribute to adequate treatment and, as a result, improve the health of the population.

Immunoglobulin E (IgE) and mast cells play a key role in various allergic diseases. Treatment with omalizumab, a monoclonal anti-IgE antibody, has significantly improved the control of these diseases and ushered in a new era in the treatment of severe allergic conditions. Long-term experience with omalizumab in severe allergic asthma has confirmed its effectiveness and safety, reducing the symptoms and incidence of severe exacerbations in patients. In addition to treating severe asthma, Omalizumab has been approved for the treatment of chronic spontaneous urticaria (CSU), and although the mechanisms underlying the action of omalizumab in CSU are not fully understood, almost 90% of CSU patients show complete or partial response to omalizumab treatment. Omalizumab has also recently been approved for the treatment of severe Japanese cedar pollinosis (JC) based on the successful results of a study of omalizumab in inadequately controlled severe hay fever treated with antihistamines and nasal corticosteroids. In recent years, there have been a number of scientific publications showing the successful off-label use of omalizumab in diseases in which IgE plays a key role such as allergic rhinitis, allergic bronchopulmonary aspergillosis, anaphylaxis, keratoconjunctivitis, food allergy, drug allergy, non-atopic asthma, mastocytosis, atopic dermatitis, nasal polyps, Churg-Strauss syndrome, eosinophilic otitis media, chronic rhinosinusitis, bullous pemphigoid, systemic lupus and contact dermatitis. Its safe use in pregnant women with asthma, as well as the concomitant use of omalizumab and allergen-specific immunotherapy, has already been confirmed. Therefore, the potential for omalizumab in other chronic conditions should be considered. [ABSTRACT FROM AUTHOR]

The aim of the study was to study the dynamics of clinical and allergic characteristics of patients with allergic rhinitis (AR) in Samara over the past 5 years. Clinical and allergological examination was performed in 1526 patients from 2012 to 2018. For skin prick testing, 16 names of standard allergens were used. In 2018, the most common forms of AR were seasonal – 40.7 % and combined (seasonal and perennial) forms of AR – 39.8 %. Over the past 5 years, there has been a 1.5-fold increase in seasonal forms of AR (pollinosis). The structure of sensitization revealed an increase in pollen allergy from 39.2 % to 50.6 %, and a decrease in the level of hypersensitivity to epidermal allergens from 29.9 % to 14.5 %. Sensitization to weeds remains dominant in patients with pollinosis and ranges from 82.8 % to 75.2 % in 2012 and 2018, respectively. The predominance of polysensitization to different groups of allergens over monosensitization remains: 55.8 % and 44.2 %, respectively.

At the present time, the efforts of many research groups around the world are aimed at finding new factors triggering the allergic sensitization process linked with IgE synthesis to harmless allergens. According to the recent data, production of tissue cytokines is induced in tissue cells by alarmins, thus, in turn, eliciting pro-allergic immune response. Previously we have shown that β-alanine could be a potential alarmin capable to stimulate production of tissue cytokines. The aim of this work was to determine the impact of β-alanine on humoral immune response in low-dose allergy model. BALB/c mice were immunized by recombinant Asp f 2 protein or commercial ovalbumin (OVA) in the withers 3 times a week with or without β-alanine supplementation. To determine the mechanism of β-alanine effect, α-L-alanine, an isomer which is not MrgD receptor ligand, and β-aminoisobutyrate with β-alanine-like affinity to MrgD ligand, were compared. According to our data, β-alanine stimulated specific IgE and IgG1 production in a short-term course (7 immunizations) and enhanced antibody affinity after long-term (14 immunizations) protocol in the case of low-immunogenic protein Asp f 2. In the case of high-immunogenic OVA protein, the impact of β-alanine was significant only upon antibody affinity. Hence, β-alanine accelerates specific IgE production in the case of low-immunogenic protein. The impact of β-alanine on specific IgE production was not linked to specific MrgD receptor activation, because β-aminoisobutyrate, which is the other ligand of this receptor, did not have a similar effect upon humoral immune response. The effect of β-alanine on IgG1 production seems also independent of MrgD receptor, since the common proteinogenic amino acid α-L-alanine also enhanced specific IgG1 production. The effect of β-alanine on humoral immune response could be linked to its non-specific action, e.g., due to its ability to induce oxidative stress through blocking taurine transporter, or due to its ability to stimulate cellular metabolism.

Background. Malformations in epidermal barrier in children with atopic dermatitis (AD) can cause transcutaneous sensitization with further development of allergic diseases that can worsen the AD course and significantly reduces patients’ quality of life.Objective. The aim of the study was to determine the effect of topical treatment and maintenance therapy with pimecrolimus 1% cream (PIM) and topical glucocorticosteroids (tGCS) in infants with AD on reducing the risk of developing transcutaneous sensitization (due to the levels of specific IgE to the cow milk protein over time) and on reducing the disease severity (by the EASI scale).Methods. The study included children aged from 1 to 4 months with early manifestations of moderate and severe AD. The severity of AD was estimated via the EASI scale at start of observation, then at 6, 9 and 12 months of life. The class and level of specific IgE to cow milk proteins (CMP) were determined by the ImmunoCAP method at the point of enrolment and at the ages of 6 and 12 months. Statistical analysis of studied indicators dynamics and their comparison in research groups was carried out using multifactorial dispersion analysis.Results. The study included 36 patients. All patients have received standard tGCS therapy in combination with emollients (wet wrap) for 10 days. The maintenance therapy was prescribed in postacute period. It included topical calcineurin inhibitor PIM 2 times/day for 3 months, then double application (morning/evening) 3 times/week up to the age of 1 year old (group 1). Other group had maintenance therapy — tGCS2 times/week for 3 months, and then at AD aggravation (group 2). Group 1 has shown lower level of sensitization to CMP at the age of 6 and 12 months and more significant decrease in AD severity according to EASI scale compared to group 2.Conclusion. The treatment with PIM is effective in therapy of AD and prevention of transcutaneous sensitization in infants.

IgE plays an important role in the allergic diseases. More and more publications focus the attention ot IgE participation in non-allergic conditions. Therefore, there are already publications on the successful off-label use of anti-IgE therapy (omalizumab) in diseases such as mastocytosis, urticaria - vasculitis, systemic lupus erythematosus, bullous dermatoses and others. We present our clinical experience in the off-label application of omalizumab in 2 children: a 10-year-old boy with cystic fibrosis and aspergillosis and a 9-year-old girl with normocomplementary urticaria-vasculitis. [ABSTRACT FROM AUTHOR]

Genetic, or idiopathic, generalized epilepsies (GGEs or IGEs) includes childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and epilepsy with generalized tonic-clonic seizures alone (GTCS-a).Aim. to characterize the capabilities of electroencephalography (EEG) for the diagnosis of various forms of genetic generalized epilepsyMaterials and methods. Literature data in Pubmed, Google Scholar was analyzed. In addition, own observations and clinical cases were systematized.Results. The article presents the data of morphology and topography of spike-wave discharges, as well as other patterns of EEG in the GGE – poly-spike activity, photoparoxysmal response, occipital intermittent rhythmic delta activity (OIRDA), fixation-off sensitivity and generalized paroxysmal fast activity (GPFA), as well as epileptiform K-complexes, the allocation of which in an independent pattern is questioned by a number of neurophysiologists. The differences between interictal and ictal activity in the GGE are discussed in detail; electroencephalogram (EEG) informativity modifiers are considered. The morphology of atypical features in the GGE is considered. The role of EEG in the differential diagnosis of CAE, JAE, JME, GTCS alone with the description of typical, atypical features, study scenarios and diagnostic criteria for each form are considered.Conclusions. Typical EEG features of GGE significantly simplify the differential diagnosis of electroclinical syndromes. There are “non-classical” features of EEG in the GGE, which do not contradict the diagnosis. To reveal the peculiarities of epileptiform discharges distribution, video EEG monitoring with night-time sleep and the use of several modality stimuli is preferable. Incorrect interpretation of EEG is dangerous for the patient.

Juvenile myoclonic epilepsy (JME) is a common disease. However, some aspects of etiology and pathogenesis are not yet fully clarified. This publication describes the development of ideas about JME, the types of seizures that occur in JME, provides a list of triggering factors and a prognosis severity scale that depending on these triggering factors. The section on JME diagnostics discusses methods of neuroimaging, electroencephalography, and approaches to assessing the mental status of JME patients. The data of meta-analysis of prevalence and risk factors of refractory JME in the context of assessment of the disease state and prognosis are presented. The data on advantages and disadvantages of various Antiepileptic Drugs (AEDs) for the control of the disease are considered. The results of the own study of AED spectrum and effectiveness in gender-sensitive and ILAE-recommended therapy in adults, as well as the GENERAL study of perampanel efficacy and safety in patients with idiopathic generalized epilepsy, are presented. It confirmed the high efficacy of the perampanel primarily for myoclonic seizures and generalized tonic-clonic seizures. A case study of a female patient with JME was also described, in which refractory to therapy was noted, including due to low compliance to the prescribed therapy.

The paper presents evidence that the individuals with different blood groups and glucose levels exhibit individual IgE reagin responses to insulin. Thus, the persons with 0 (I) blood group showed the highest values of anti-insulin-specific IgE (124.83±67.9 kE/L) when their glucose level was under 4 mmol/l. Such values are characteristic to the patients with A (II) and B (III) blood groups with normal glucose levels. Among subjects with B (III) blood group showing decreased glucose values (< 4 mmol/L), the lowest insulin induction (0.85±0.05 mkE/ml) was observed, and the IgE production to insulin increased 80-fold, reaching 113.0±56.0 kE/L. At the first ("borderline") stage of carbohydrate metabolism disorders (glucose levels 6.0 to 7.6 mmol/L), the insulin production is increased 3-fold in 0 (I) and A (II) blood groups, whereas insulin levels in persons with B(III) blood group are near-normal (12.3±3.7), and IgE antibodies to insulin show lowest levels (27.2±9.08 kE/L), thus being 5 times lower when compared to the persons with B (III) blood group. However, carriers of all three group antigens and patients with expressed type 2 diabetes respond to increased glucose and insulin levels in blood by decreased production of specific IgE antibodies to insulin.

61 people suffering from persistent allergic rhinitis and asthma accompanying food allergies were studied using case histories, the NHANES questionnaire, polyspecific serum levels, allergen-specific IgE, IL4, IFNg and IL10 assays, and allergy skin tests. Four different endotypes have been identified, including entopic, which can be the basis for new approaches to the diagnosis and treatment of allergic rhinitis and asthma.

Goal. To determine the blood serum level of α2-macroglobulin (α2-MG), α1-antitrypsin (α1-AT), lactoferrin (LF) and albumin in patients with IgE-mediated and IgE-independent atopic dermatitis (AD). Materials and methods. The authors tested blood serum of 60 adult patients suffering from atopic dermatitis at the exacerbation stage (30 patients with IgE-mediated and 30 patients with IgE-independent atopic dermatitis) and 20 healthy donors in order to determine the level of these proteins by rocket immunoelectrophoresis, enzyme-linked immunosorbent assay and immunoturbidimetry methods. Major results. The albumin level is reliably reduced in case of IgE-mediated AD while the LF and α1-AT levels are increased, and concentrations of LF α1-AT and a2-MG are increased as compared to healthy people. There are differences between the level of LF, α2-MG and α1-AT. There was a statistically significant correlation between the LF levels and SCORAD score in both forms, and α2-MG and α1-AT only in case of IgE-independent AD. Conclusion. These results confirm the difference in the roles of these polyfunctional proteins in the pathogenesis of IgE-mediated and IgE-independent AD.

Numerous observations of patients with bronchial asthma (BA) vaccinated against pneumococcal infection indicate a significant reduction in the frequency of exacerbations and hospitalisations after immunisation. Several studies have considered pneumococcal vaccines as potential immunoregulators that improve the clinical course of BA through modulation of the immune response. However, due to disease heterogeneity and different vaccine preparations, interpreting the results has serious limitations. The aim of the current work was to perform a comparative analysis of the levels of key cytokines characterising the formation of BA endotype in patients after administration of conjugated pneumococcal vaccine. Blood sera (n=31) from PCV13 (Prevenar 13) immunised patients with BA were analysed by ELISA for Th1/Th2/Treg cytokines (IFN-γ, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, and MCP-1) and the level of total IgE. The data collection time points in the study were initially, 6 weeks, 6 and 12 months after vaccination.The results of the study indicate that vaccination against pneumococcal infection using a PCV13 in patients with BA was accompanied by high clinical efficacy, regardless of the disease endotype. This was evidenced by a decrease in the number of patients with BA exacerbations and an increase in the number of patients without hospitalisations during the year of observation. The clustering of patients according to their inflammatory profile enabled the identification of specific patterns of change in the cytokine profile. These included a statistically significant increase in the concentration of IFN-γ in serum 6 weeks after immunisation in patients with the T2-«high» asthma endotype. Statistically significant alterations were observed in patients with atopy and elevated total IgE levels in serum, which exhibited a peak increase in IFN-γ concentration also 6 weeks after vaccination. Conversely, no significant changes in cytokine levels were observed in patients with T2-«low» asthma endotype within a year after vaccination.Conclusion: the results of the study demonstrated that IFN-γ plays a significant role in the potential adjustment of the immune status of patients with T2-«high» asthma endotype following immunisation with a pneumococcal conjugate vaccine.

Increased incidence of allergic diseases worldwide reflects some mangles of the existing pharmacotherapy concept which ignores some etiopathogenetic aspects of clinical atopy. Meanwhile, understanding cellular and molecular mechanisms of allergy may create prerequisites for development of new therapeutic areas, in order to effectively influence pathogenesis points of allergic inflammation and, thus, leading to therapeutic success. The review article concerns an antagonism between the two populations of T-helper cells (Th1 and Th2) carried out mainly by the action of IFNγ produced by activated Th1, and IL-4 secreted by activated Th2 which is at the heart of modern concept on the regulation of adaptive immunity. The prospects of immunotherapy of allergic diseases based on the polarization of the immune response are discussed, i.e., an activation of Th1 responses and Th2 suppression. This functional polarization can be mediated by the innate immune receptor agonist, i.e., synthetic and natural minimally-sized biologically active fragments (MBAF) with pathogen-associated molecular patterns. In this respect, a very promising drug registered in Russia is based on the synthetic MBAF, glucosaminylmuramyldipeptide (GMDP), The liсopid immunomodulator. This is due to the fact that GMDP, being an active substance of Liсopid, is a highly specific ligand for the NOD2 receptor of innate immunity factors; it may cause activation of the NF-kB transcription factor, and production of multiple immunoregulatory cytokines. Clinical and immunological efficacy of Licopid application in conventional therapy of atopic allergic diseases (asthma, atopic dermatitis, atopic variant of acute obstructive bronchitis) is presented as an overview of pre-clinical and clinical trials.

Some features of peripheral bood basophil activation were studied in children with different types of chronic urticaria, in order to specify the sustaining mechanisms of chronic urticaria. This study presents comparative data concerning spontaneous basophil activation, IgE level and Th2 helper cells. We observed forty-seven children with chronic urticaria, seventy children with exacerbated atopic dermatitis with different disease severity, fifteen healthy children without signs of allergy, or pseudo-allergy. High degree of the basophil activation was detected in children with exacerbation of atopic dermatitis (a comparison group), which was different from the groups of healthy children and patients with chronic urticaria. Spontaneous basophile activation was higher in children with chronic urticaria than in healthy children, as influenced by immune and non-immune pathogenetic factors of the disease. A positive pairwise correlation was shown between total IgE level, and Th2 helper cell numbers in peripheral blood in patients with chronic urticaria, thus confirming a Th2 immune shift. The results obtained contribute to our understanding of immune pathology in chronic urticaria.

The article covers modern approaches to the prevention of allergic diseases in children. We discuss the most common food allergens in the early childhood, main mechanisms of food tolerance formation and opportunities of dietary preventive measures in a risk group of the allergy development. One of the important issues, in practical terms, is the question of time and peculiarities of the complementary feeding introduction in this category of children. The own experience of use of hypoallergenic complementary feeding products in children from the risk group and with mild manifestations of atopy is presented.

Abstract. The study performed has shown a positive clinical and immunological dynamics in forty children with medium-stage atopic bronchial asthma in remission stage, after a course of adaptation for periodical hypobaric hypoxic stimulation. These changes were expressed as a reduction in IgE, circulating immune complexes, Interleukin-4, and rise in Interferon-γ and Interleukin-18 contents. A retrospective analysis has shown that a more stable positive clinical and immunologic effect is observed in the group of patients with relatively low IgE levels observed after hypobaric hypoxic stimulation.

Abstract. Expression characteristics of transcription factor PAX-5 (paired box 5) are considered for different clinical variants of bronchial asthma (BA). Low levels of PAX-5 expression may be a reason for progression into a severe allergic asthma, whereas higher levels of PAX-5 expression may represent a significant factor leading to development of non-allergic bronchial asthma. Initiation of IgE production is supposed to be a less important PAX-5 function in BA pathogenesis, than prevention of B-cell-to-plasmocyte differentiation. Further investigations of PAX-5 properties and its co-operations with other transcription factors may provide a promising path in further research of BA pathogenesis.

Abstract. With the purpose of establishment of the role of IL-4, IL-13 and IFNγ cytokines in regulation of the general IgE synthesis in serum of patients with different forms of tick-borne borreliosis, 31 patients have been surveyed. The received results have revealed that patients with ITBB irrespective of the level of the general IgE synthesis can be divided into two subgroups. In a subgroup of patients with the increased level of the general IgE, identical dynamics of proinflammatory and anti-inflammatory cytokines, describing the prevalence of the Th2 immune response has been observed. In patients with the reduced level of this antibody the mixed Th1/Th2 type and more smooth course of the illness were observed. Also, direct correlation between high level of the general IgE in serum and IgM titer was shown.

Abstract. Associations between I105V and A114V gene polymorphisms of glutathione-S-transferase P1 and levels of IgE and secretory IgA in tear fluid were studied in steelworkers with or without ocular diseases, as compared with healthy office employees. Genotyping was performed by means of allele-specific polymerase chain reaction, whereas ELISA technique was used for immune testing. We have found that IgE levels in tear fluid was increased in steelworkers with dystrophic eye diseases, pinguecula/pterygium, and healthy steelworkers, in comparison with control group. This increase correlates with pinguecula/pterygium size and with their industrial employment terms. Secretory IgА levels in tears were decreased in these groups of workers, as compared with controls. Concentrations of both immunoglobulins in tear samples depended on I105V and А114V glutathione-S-transferase P1 gene polymorphisms. I105V polymorphism correlated with lower concentrations of tear IgЕ in steelworkers with ocular dystrophic diseases and healthy metallurgists. А114V polymorphism is connected with decreased quantities of tear IgЕ in steelworkers with ocular dystrophic diseases, as well as with the lower amounts of secretory IgА in healthy workers and administrative staff. Hence, polymorphic loci I105V and А114V of glutathione-S-transferase P1 gene may exert a modulatory effect upon biosynthesis of both Ig types. (Med. Immunol., 2011, vol. 13, N 6, pp 609-616)

Abstract. The review article concerns various features of PAX-5 (paired box 5) transcription factor, its structure, functions, regulation of activity, involvement into differentiation and activation of B lymphocytes, switching to IgE synthesis, its role in oncogenesis, and a putative role of this factor for development of bronchial asthma.Further insight into specific properties of PAX-5 factor in bronchial asthma may provide a promising approach to studying mechanisms of this disorder. (Med. Immunol., 2011, vol. 13, N 6, pp 569-580)

The present investigation was planned to explore stress induced changes in the levels of IgE by correlating them with the important parameters of stress like cortisol and free radical scavengers in the serum of Indian dromedaries. The mean values of serum IgE and cortisol were significantly (p ≤ 0.05) higher in wound affected dromedaries than the respective healthy values. A positive significant (p ≤ 0.05) correlation was observed between the values of serum IgE and cortisol. The mean values of serum vitamin C, vitamin E and glutathione decreased whereas of serum catalase, superoxide dismutase, monoamine oxidase, glutathione reductase, xanthine oxidase, oxidase and peroxidase increased significantly (p ≤ 0.05) from their respective healthy mean values. A negative significant (p ≤ 0.05) correlation was observed between the values of serum IgE and vitamin C; serum IgE and vitamin E and serum IgE and glutathione activities. A positive significant (p ≤ 0.05) correlation was observed between the values of serum IgE and catalase; serum IgE and superoxide dismutase; serum IgE and monoamine oxidase; serum IgE and glutathione reductase; serum IgE and xanthine oxidase; serum IgE and oxidase; and serum IgE and peroxidase activities. It was concluded that stress was able to induce marked changes in the levels of IgE in the Indian dromedaries. Wounds altered the immune status as well as levels of cortisol and free radical scavengers in the serum.

Aim. To discover relations between allergic diseases and H.pylori infection in patients with gastroduodenal diseases. Material and methods. The study was made of 113 patients (age 22-65, 34 males and 79 females) with chronic gastritis and duodenal ulcer. Of them, 60 patients (group 1) had concomitant allergy (urticaria, bronchial asthma, atopic dermatitis, food allergy, pollinosis), while 53 patients (group 2) had no allergy. H.pylori infection was diagnosed with the respiratory and rapid urease test, histological and cytological tests. Enzyme immunoassay determined total antibodies (AB) to H.pylori in IgG, IgA, IgM classes; IgA-AB in the kits Vector Best (Russia), IgG-AB to H.pylori in the kits of ECOLab (Russia) and total IgE in the kits IgE-EIA (Stavropol). Results. In group 1 total AB to H.pylori were positive in 48 (80%), IgG-AB and IgA-AB to H.pylori in 38(63.3%) and 43 (71.6%) patients, respectively. In elevated concentration of AgG-AB to H.pylori 46 (76.6%) patients had elevated total IgE (mean 364 IU.l). In group 2 total AB to H.pylori were detected in 45 (85.0%) patients, IgG-AB and IgA-AB to H.pylori in 47 (88.6%) and 32 (60. 3%), respectively. Among patients with high level of IgG-AB to H.pylori in the serum high total IgE was only in 35.8% patients. Mean IgE was 250 IU/l. Conclusion. Patients with gastroduodenal diseases associated with H.pylori and allergy and not associated had similar level of total AB to H.pylori, while higher total IgE and specific IgE-AT to H.pylori occurred in the former. Thus, H. pylori infection is associated with allergic (atopic) immune response.

At present, there are sufficient data on the influence of the gut microbiome on the development of food allergy and its progression. Changes in gut microbiome composition could positive impact on the course of allergic diseases by means of regulating the ratio of pro- and anti-inflammatory cytokines, as well as immunoglobulin E level. The purpose of the research was to study the effectiveness of combined probiotic in treatment of food allergies in children. Material and methods . The prospective randomized controlled study included 92 children aged from 4 to 5 years with symptoms of food allergy, involving the skin and gastrointestinal tract. The main group (n=46) took two chewable tablet Bifiform Kids (Lactobacillus rhamnosus GG >1x10 9 CFU, Bifidobacterium animalis spp. lactis BB-12 >1x10 9 CFU, thiamine mononitrate 0.40 mg, pyridoxine hydrochloride 0.50 mg per tablet) 2 times per day during 21 days. The control group (n=46) did not take the complex. The dynamics of the severity of food allergy skin symptoms was assessed using the SCORAD index, of gastrointestinal manifestations - on a point scale after 21 days and after 4 and 6 months (visits 2, 3 and 4). The concentration of immunoglobulin E, interleukins IL-17 and IL-10 was determined by enzyme immunoassay in blood serum at the baseline, as well as after 21 days and after 6 months (visits 1, 2 and 4) after the study initiation. Results . The SCORAD index among children from the main group decreased from 12.4±2.3 до 7.6±1.8 (р=<0.05) while taking a combined probiotic. It was significantly lower (р=<0.05) compared to the control group (SCORAD index changed from 12.1±2.4 to 12.2±1.9). On the 21st day, a statistically significant decrease in level of pro-inflammatory IL-17 (by 27%) and a statistically significant increase in the concentration of anti-inflammatory IL-10 (by 38.9%) were recorded. In children from the main group, the severity of such gastrointestinal symptoms as pain, rumbling in the abdomen, belching with air, bloating, gas discharge, increased stool and its unformularity, decreased compare to the control group of patients (р=<0.05), in which the intensity of complaints related to gastrointestinal manifestations did not change. In the main group of patients, the most clinical efficacy was noted immediately after the end of the probiotic intake. In the following five months, the intensity of symptoms increased in individual subjects from the main group, but in general, the intensity of complaints remained significantly lower than before probiotic intake (р=<0.05). Children from the main group showed a significant decrease in IgE level from 184±121 kU/l by 43.5% at visit 2 and by 38.0% at visit 4 (p=<0.05), while in children from the control group its level didn't change, amounting to 176±141, 165±121 and 178±132 kU/l, respectively. Conclusion . The results of the study show the effectiveness of the use of a combined probiotic (Lactobacillus rhamnosus GG, Bifidobacterium animalis spp. lactis ВB-12) with vitamins B1 and B6 in children with mild forms of gastrointestinal and skin manifestations of food allergy, both in relation to the severity reduction of the clinical symptoms of the disease (skin manifestations, pain, rumbling in the abdomen, belching with air, bloating, gas discharge, increased stool and its unformularity), and in relation to the dynamics of biochemical parameters - a decrease in the level of IgE., Competing Interests: The author declares no conflicts of interest., (Copyright© GEOTAR-Media Publishing Group.)

Probiotics are widely used as a means of dietary correction of the intestinal microbiota in patients not only with alimentary, but also with allergic and inflammatory diseases. They have systemic effects on the human organism. However, the diversity of the composition of probiotic complexes complicates the determination of the beneficial effects of specific microorganisms on the human body. These circumstances call for more research. Investigation of the effect of probiotic intake on the levels of various cytokines may explain the mechanisms of the beneficial effect of probiotic intake on the functioning of the immune system. Objective - to study the effectiveness of the probiotic Bifiform Kids for the prevention of respiratory infections in children with recurrent respiratory infections with gastrointestinal allergy symptoms. Material and methods . The prospective randomized controlled trial included 92 children aged from 4 to 5 years who suffers from more than 5 episodes of respiratory infections per year with gastrointestinal allergy symptoms. Patients from the main group (n=46) were prescribed 2 chewable tablets Bifiform Kids (Lactobacillus rhamnosus GG not less than 1×109 CFU, Bifidobacterium animalis spp. lactis not less than 1×109 CFU, thiamine mononitrate 0.40 mg, pyridoxine hydrochloride 0.50 mg in each) twice per day within 21 days. Patients from the control group (n=46) were prescribed no probiotics during the study period. The study included the measurement of blood serum levels of immunoglobulins A, M, G (by immunoturbodimetry) and E, as well as the concentration of cytokines IL-17, IL-10 (by enzyme immunoassay). Measurements were performed at the 1st day of the study, at the 21st day of the study, and 6 months after the study initiation. The microbiota composition was determined by sequencing the bacterial 16S rRNA genes in DNA preparations isolated from stool samples collected at the start of the study and after 21 days. The Shannon index was calculated for the species of detected bacteria to determine the diversity of the microbiome. The effectiveness of disease prevention was measured by calculating the prevention index and the efficiency coefficient based on the incidence of respiratory infections in both groups during the observation period (6 months). Results . In the main group, the volume of the commensal flora decreased 3 weeks after the study initiation: Enterobacter from 18.3±19.3 to 10.5±18.1%; Enterococcus from 8.7±16.1 to 3.1±10.0%; Clostridium from 3.1±8.1 to 0.5±2.2%. There was a statistically significant increase in the proportion of representatives of the genus Bifidobacterium by 2.2 times (from 16.9±26.4 to 36.5±31.5%, p=0.0017) and a decrease in the Shannon index from 1.1±2.1 up to 0.4±1.1 (p<0.05). In the control group, there were no statistically significant changes in the microbiota content. In the main group, after 21 days, the blood IL-10 level increased from 11.3±15.4 to 15.7±13.4 pg/ml, and the IL-17 concentration decreased from 8.9±7.7 to 6.5±7.1 pg/ml (p=<0.05) while maintaining this trend by the 6th month of observation. There were no changes in these indicators in children from the control group. The main group demonstrated a significant (р=<0.05) decrease in the level of IgE from 184±121 to 104±67 and 114±54 kU/l, and a significant increase in IgA from 0.73±0.45 to 1.33±0.65 and 1.21±0.57 g/l after 3 weeks and at the end of the probiotic intake, respectively. The level of IgA in the main group remained higher during the study compared to the control group. The main group demonstrated a 3-fold decrease in the incidence of respiratory infections in comparison with the control group. The efficiency index was 3.21, the therapeutic response was 69%. Conclusion . The results of the study show the effectiveness of the complex probiotic for the respiratory infections prevention in children with gastrointestinal allergy symptoms., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)