Autism spectrum disorders are associated with an imbalance of immune and neurological disorders, starting after the age of two. The study is devoted to studying the role of specialized strains of bacteria Lactobacillus reuteri, which mediate the synthesis of oxytocin in humans and influence inflammation indicators. Bacteria of this strain were part of the biologically active additive “Panbiolact Mental”, developed and presented by NPO ArtLife (Tomsk). The purpose of the work was to assess the effect of specialized strains of bacteria Lactobacillus reuteri on changes in the composition of the intestinal microbiota, oxytocin levels, and immune parameters of children with ASD. The study included 43 children with autism spectrum disorders who took Panbiolact Mental for 90 days. The study materials included venous blood samples and fecal samples. The concentrations of cytokines (IL-4, IL-10, TNF, IFN), immunoglobulins (IgE, IgG, IgA, IgM) and the neuropeptide oxytocin were determined in the blood serum. Fecal samples were used to assess the qualitative and quantitative composition of the colon microbiota. Clinical symptoms of the disease associated with quality of life were assessed using the standard ATEC test scale (Autism Treatment Evaluation Checklist), expressed in scores corresponding to the severity of clinical and neurological parameters of the disease. In children with autism spectrum disorders, after 90 days of regular use of Panbiolact Mental, the number of bacteria of the genera Acinetobacter decreased, the number of Bacteroides species pluralis, Akkermansia muciniphila, Eubacterium rectale, Prevotella species pluralis and Methanobrevibacter smithii increased. Increases in the concentration of oxytocin, the protolerogenic coefficient IL-10/TNFα, immunoglobulins M and G, and a decrease in the concentrations of TNFα and IL-10 were recorded. The results of the study support the hypothesis of a significant role of gut microbiota diversity in the neuro-immune pathogenesis of autism spectrum disorders. “Panbiolact Mental” is presented as a potentially effective remedy for an integrated approach to the correction of ASD in children. These data may form the basis for further research in the field of probiotic therapy, as well as for the development of new strategies based on modulation of the intestinal microbiota.

People need to eat and digest food, and if they encounter a food allergy it is a real problem. Moreover, some people have a lifelong sensitization to certain products with the threat of anaphylaxis. This chapter considers different aspects of food allergies, allergenicity of dietary allergens, the significance of the gut microbiota and intestinal epithelium integrity, detailed processes of food sensitization, clinical phenotypes and management of food allergies, and, finally, mechanisms of oral tolerance. Fortunately, the gastrointestinal tract possesses robust tolerogenic mechanisms, in particular, the beneficial gut microbiota, as well as the autonomous enteric nervous system, which taken together with the gut immune cells and molecules may be called the enteric neuroimmune system (ENIS). The dual-allergen exposure hypothesis postulates that early oral exposure to food allergens induces tolerance, whereas exposure at non-gastrointestinal sites results in food sensitization and allergy development. In addition, a series of food allergic episodes does not look like a typical atopic disease and is a known exception to the rule conceived by evolution. However, the prevalence of food allergies is continuously growing, including severe cases, and it is a paradoxical problem in the face of evolution. This challenge is inherent to our civilization and will be resolved, thanks to new knowledge and technologies.

Metabolic syndrome (MS) is a serious medical and social problem due to its high prevalence, lack of common approaches to diagnosis and treatment. Prevention of food dysadaptation reactions and the studies of control mechanisms of immune tolerance to food antigens is of special scientific interest, thus providing available anti-inflammatory tools for correcting increased permeability of the intestinal epithelium and vascular endothelium associated with development of MS. Nutritional dysadaptation occurs due to inappropriate diet being mediated by the geno-phenotypic characteristics of digestive enzymes and immune system which control the efficiency of food digestion.Immunological control of digestion, including dynamic maintenance of tolerance to food antigens, is carried out at two levels of immune system: innate response with functional involvement of microbiota, and adaptive response, represented by cellular and humoral mechanisms associated with molecular epitopes and critical mass of persistent food antigens which are present in immunologically competent areas of small intestine, due to changing permeability of intestinal barrier and transcytosis processes. Patients and methods: aiming for assessment of the diet contribution to the immuno-biochemical and rheological imbalance in people with increased body weight, 170 volunteers of both sexes aged 20-55 years were examined, depending on the body mass index: > 27.0 kg/m2 (clinical group, n = 120), and those with BMI of < 25.0 kg/m2 (control group, n = 50). We have revealed statistically significant increase of multiple parameters in the clinical group, i.e., concentration of IL-6, IL-17, cholesterol, glucose, glycosylated hemoglobin, insulin, indices of insulin resistance and atherogenicity. Increased levels of specific IgG antibodies to a number of food antigens were found in the subjects in the clinical group. In the course of our study, a statistically significant relationships was found between total numbers of platelets (p < 0.05; r = 0.213), erythrocytes (p < 0.05; r = -0.211), mean erythrocyte volume (MCV) (p < 0, 05; r = 0.339), and the concentration of IgG to casein in the blood, as well as a correlation between the levels of sIgG to soybeans and the number of platelets (p < 0.05; r = 0.231). At the same time, some associations were found between the established values of IgG to casein pAG, and the risk of developing atherogenic changes (atherogenicity index > 3) being significant at OR = 2.68 (1.33-5.42), as well as between IgG values to casein pAG (OR = 8.9 (2.6-30.5)), to soybean pAG (OR = 5.6 (1.8-16.7)), to gluten pAG ((F = 0.00359. p < 0.05), and increased body mass index.The results obtained were interpreted as a possible impairment of food tolerance for a number of food antigens in individuals with high body mass index, due to the revealed correlations between concentrations of IgG to food antigens, imbalance of pro-inflammatory cytokines, rheological and metabolic parameters. These data may be used as biomarkers suggesting higher risk of evolving metabolic syndrome.

Immune cells and immune-derived molecules, endocrine glands and hormones, the nervous system and neuro molecules form the combined tridirectional neuroimmune network, which plays a significant role in the communication pathways and regulation at the level of the whole organism and local levels, in both healthy persons and patients with allergic rhinitis based on an allergic inflammatory process. This review focuses on a new research paradigm devoted to neuronal-immune cell units, which are involved in allergic inflammation in the nose and neuroimmune control of the nasal mucociliary immunologically active epithelial barrier. The categorization, cellular sources of neurotransmitters and neuropeptides, and their prevalent profiles in constituting allergen tolerance maintenance or its breakdown are discussed. Novel data on the functional structure of the nasal epithelium based on a transcriptomic technology, single-cell RNA-sequencing results, are considered in terms of neuroimmune regulation. Notably, the research of pathogenesis and therapy for atopic allergic diseases, including recently identified local forms, from the viewpoint of the tridirectional interaction of the neuroimmune network and discrete neuronal-immune cell units is at the cutting-edge.

Autistic spectrum disorders (ASD) affect about one in every 59 children. It is noteworthy that patients with ASD are more likely to have other comorbidities than the general population. Undoubtedly, they may aggravate clinical course of the underlying disease or affect the diagnostics. The aim of this work was to identify clinical and immunological phenotypes of the ASD clinical course. Patients and methods. The study included children classified in 2 groups: pediatric patients with ASD (n = 100), and clinically healthy children (n = 30). Based on the presence of comorbidities, the children were divided into 3 types of clinical patterns: convulsive, infectious, dermato-respiratory and gastrointestinal phenotypes. Cytokine concentrations in blood serum were determined by ELISA using Bender Medsystems (Austria) for IL-17А and Vector-Best (Russia) for IL-4, IL-6, IL-10, IFNγ. The concentration of spIgG to 111 nutritional antigens (IgG) was determined by a modified ELISA method using the Immunohealth™ technique. Assessment of cognitive and psychophysiological indices in children was carried out using the ATEC questionnaire. As a result of the study, clinical and immunological phenotypes were identified among the ASD patients, being associated with certain types of food tolerance, cytokine profile, clinical severity of psycho-physiological disorders and concomitant comorbid diseases. In all four phenotypes, were have revealed an increased synthesis of specific antibodies associated with humoral immunity for the studied food antigens, increased concentration of total spIgG to food antigens, concentration of spIgG to legumes and casein, and C-reactive protein levels.Moreover, in convulsive phenotype (concomitant epilepsy and convulsions), the maximal concentrations of spIgG are shown for Solanaceae products, the concentration of IL-10 is increased, IL-4 amounts are reduced, and the content of serum iron and ferritin is also lowered. In the infectious phenotype (frequently ill children) the spIg’s to grain and fermented products are detected, IL-10 and IFNγ concentrations are increased and IL-4 contents is reduced, along with increased absolute and relative number of lymphocytes and fibrinogen. In the dermato-respiratory phenotype (skin rashes) – to dairy products, the concentrations of IL-4 and IL-17A are increased. In the gastrointestinal phenotype, the highest number of elevated IgG responses to the largest range of food antigens was found in presence of changing cytokine profile , i.e., an increase in IFNγ in IFNγ/IL-4 and IFNγ/IL-10 ratios. Thus, the identified phenotypes of the ASD course are associated with the influence of food antigens and reflect a special variant of the immunological inflammatory pathogenesis, which makes it possible to personalize elimination diets, propose measures for correction and individual prevention, and, probably, to predict clinical course of the disease.

The aim of the study: to reveal the particularities of the concentration of cytokines IL4, IL6, IL10, IL17, IFNγ in blood serum in children with autism spectrum disorder (ASD).Materials and methods. The blood samples obtained from children of two study groups: children with autism spectrum disorder (n = 93) and clinically healthy children (n = 30), served as the material for the study. Cytokine concentrations were determined in blood serum using the Bender Medsystems (Austria) kits for IL17A and Vector-Best (Russia) kits for IL4, IL6, IL10, IFNγ. Serum cytokine concentrations were determined by enzyme immunoassay using kits for IL17A (Bender Medsystems, Austria), IL4, IL6, IL10, IFNγ (Vector-Best, Russia). Assessment of cognitive and psychophysiological indicators in children was performed using the Autism Treatment Evaluation Checklist (ATEC).Results. The concentrations of IL17A (U = 54; p = 0,015) and IFNγ (U = 4.64; p = 0,006) were increased and the concentrations of IL6 (U = 327; p = 0.001) and IL4 (U = 177; p = 0.001) were decreased in children with ASD. The concentration of IL6 correlates with the concentration of IL4 (r = 0.68; p < 0.05). The concentration of IL17A correlates with the concentration of IFNγ (r = 0.41; p < 0.05), IL6 (r = 0.87; p < 0.05) and ATEC score (r = 0.24; p < 0.05) in the group of children with ASD.Conclusion. The cytokine disbalance in children with ADS, which was observed in our study, confirms the hypothesis of their participation in the development of the disease and clearly shows the Th17 immunoregulation pathway in the pathogenesis of the autism spectrum disorder.

Urticaria is a serious medical and social problem due to its high prevalence, lack of unified approaches to diagnosis and treatment, with high financial costs for therapy and rehabilitation. Long-term recurrent course of the disease, resistance to traditional methods of therapy lead to a significant decrease in the quality of life of patients with chronic urticaria. Itching accompanying this disease leads to deterioration in the patient’s general well-being, frequent sleep disturbances and, as a result, significant decrease in working capacity. Up to the present moment, etiopathogenesis of urticaria is a complex challenge due to the multivector nature of cytokine response, interference of protides of the complement system, patterns of kininbradykinin interference, peculiar expression of the immune response. The problem of current population is lipotrophy – chronic, heterogeneous, cytokine mediating, progressive inflammatory disease attributed by abnormal accumulation of excessive adipose tissue. Adipose tissue, being a sporadic organ of endocrine system secretes multiple hormone-like substances, mediators, cytokines and chemokines which have been given a common name, i.e., adipokines or adipocytokines. True signs of destructive parenchymal changes of liver in the form of increasing bilirubin and AST, decreasing level of vitamin D in patients with chronic recurrent urticarial in presence of obesity have been revealed during the study performed. The action of cytokines, as mediators of intercellular interaction is closely related to the physiological and pathophysiological responses of the body with modulation of both local and systemic defense mechanisms. It is assumed that the cytokine status of patients with chronic urticaria is dominated by cytokines that increase allergic inflammation of the skin. Analysis of 12 T regulatory biomarker concentrations revealed increased concentrations of IL-10, IL-19, IL-20, IL-27, IL-35, IFNλ2 and IFNλ1 in blood serum of patients with chronic urticaria. It was found that in the group of patients with chronic urticaria and increased body mass index (BMI), the level of all investigated T regulatory cytokines is lower than in the patients with normal BMI, except for IL-10. Decreased levels of biologically active IFN I (α/β) and, especially, IFN II (γ) types of blood leukocytes in patients with chronic urticaria were revealed. The levels of 12 Treg cytokines were determined in blood serum of patients with chronic urticaria, showing trend for imbalance of Treg cytokines: IL-10, IL-19, IL-20, IL-27, IL-35, IFNλ2 and IFNλ1.

The paper considers the role of mineral elements in patients with food hypersensitivity with an assessment of their contribution to the development of metabolic disorders. The study performed a comparative analysis of the concentration of 29 macro- and microelements with a simultaneous assessment of the immunological and biochemical parameters in patients with an increased body mass index in comparison with volunteers with a normal body mass index. We established relationships between the serum lipid profile and lead (Pb) concentration in hair samples: Pb and cholesterol ( Rs = 0.38; p < 0.05), Pb and LDL ( Rs = 0.33; p < 0.05), and Pb and the atherogenicity index ( Rs = 0.34, p < 0.05). We found an inverse correlation between the serum IL-6 concentrations and zinc in the hair samples ( Rs = –0.45, p < 0.05), as well as a correlation between milk hypersensitivity and the calcium (Ca) concentration in hair samples: Ca and IgG to casein ( Rs = –0.54; p < 0.05), Ca and IgG to cow’s milk ( Rs = –0.36; p < 0.05), and Ca and IgG to cottage cheese ( Rs = –0.52; p < 0.05). The results of this study show the role of macro- and microelements as significant predictors in the development of metabolic disorders.

According to world statistics, the incidence of autism spectrum disorders (68–100 cases per 1000 births) continues to increase in the children’s population, with boys predominating over girls (6–8: 1) [4]. Despite numerous studies on this problem, the pathogenesis of autism remains controversial. The purpose of this work is to study the clinical and immunological interactions of IgG mediated food hypersensitivity, cytokine balance and psychological parameters in children with autism spectrum disorders living in Tomsk. As a result, it was noted that children with autism are statistically significantly more often hypersensitive to cereals and dairy. Revealed changes in the concentration of a number of interleukins in the serum. A direct correlation was found between the concentration of IgG to antigens of the fungi of the genus Candida, food AG of dairy and grain and the concentration of IFNγ in serum.

Currently, Candida albicans is considered a predictor of chronic infl ammation and insulin resistance. The work investigated the contribution of fungal sensitization on the example of Candida albicans in the development of hypersensitivity to food antigens and manifestations of the metabolic syndrome.

Currently, the incidence of autism spectrum disorders (ASD) continues to increase in the children’s population. However, the pathogenesis of autism remains controversial.The purpose of this work is to evaluate the performance of the elimination nutritional approaches to the dynamics of indicators of food hypersensitivity, the balance of interleukins and psychophysiological parameters in children with ASD.Methods. A prospective cohort study of children aged 7 ± 2 years, healthy and diagnosed with ASD was performed. Determination of specific immunoglobulin concentrations to 111 food antigens and interleukins was measured by ELISA. Psychophysiological indicators of communicative competence in children with ASD were evaluated in the ATEC-test.Results. It was established that in children with ASD (n = 69), the frequency of occurrence of food hypersensitivity and indicators of specific sIgG concentrations to food antigens of dairy and grain products are higher (р < 0.05). A direct correlation was found between the concentration of INFγ, IgG concentrations to antigens of dairy, grain products and C. albicans. High ratios of the INFγ/IL4 and INFγ/IL10 ratios (p < 0.05) were revealed. As a result of compliance with the elimination diet was noted significant decrease in the concentration of sIgG to food antigens, sIgG to C. albicans, changes indicators following the results of ATEC testing.The data obtained revealed the unexplored effects the influence of specific food hypersensitivity on the process of initiation and maintenance of immune inflammation, as well as on the communicative competence in pathological conditions. A personalized elimination diet can improve the immunorehabilitation and the quality of life of children with autism.

In this research, we present an overview of the biometals content in serum and hair samples taken from children with autism spectrum disorder (ASD). Under the observation were 38 children with ASD (age 7.9 ± 2 years). The comparison group included 20 children without ASD symptoms (age 7.7 ± 2 years). We found elevated levels of magnesium and phosphorus (4.3 and 2.8 times), as well as iron and selenium deficiencies in hair samples collected from children with ASD. Children with ASD had a statistically significant excess cadmium content in the hair compared with the control group (U = 91, p = 0.038); an excess of toxic elements (aluminum, mercury, cadmium) was detected in the blood serum of children with ASD. It was found that the level of elements essential for the functioning of the nervous and immune systems was lower, and the amount of toxic trace elements was significantly higher in children with ASD.

The indices of the specific hypersensitivity of the immune system to 111 food antigens, divided into clusters according to related antigens, were analyzed and the connection to the main clinical and immunological parameters of inflammation in patients with metabolic syndrome was estimated. It is found that IL-17 can be a marker of food hypersensitivity. Milk protein-casein is a trigger of inflammation in patients with metabolic syndrome.

The aim of the study was to investigate the relationship between food hypersensitivity, inflammation markers and the cytokine profile in children with autism spectrum disorders (ASD). Materials and methods. The concentration of specific IgG for 111 food antigens was measured via the modified immunological method designed by the ImmunoHealth company. In addition, we performed routine biochemistry tests and immunoassay of interleukins. All children with ASD followed the recommended eliminating diet during 6 months. In order to check their physical and mental condition, their parents completed the autism treatment evaluation checklist (ATEC), both before and after the diet (Bernard Rimland and Stephen M. Edelson of the Autism Research Institute). In result, we detected the high frequency of hypersensitivity to cereal and dairy products in children with ASD. Moreover, the intensity of hypersensitivity correlated with ATEC score. We also determined that the cytokine profile in children with ASD was different from that in the control group. In particular, the concentration of IFNγ in serum, as well as the IFNγ/IL-10 and IFNγ/IL-4 ratio, were significantly higher in children with ASD. The revealed changes in the cytokine profile correlate with the specific hypersensitivity for cereal and dairy food antigens as well as with ATEC score.

The review focuses on the functional role of histamine and the genetic factors involved in maintaining the physiological level of this amine in the organism, as well as on the involvement of histamine and genes of the histamine pathway in the development of several common diseases. Histamine is a biogenic amine with a wide range of competencies, the physiological effects of which are realized with the help of four types of receptors (HRH1, HRH2, HRH3, and HRH4), characterized by tissue-specific expression. The key genes responsible for maintaining the physiological level of histamine are HDC (responsible for the synthesis of endogenous histamine), AOC1, HNMT, MAOB, and ALDH7A1 (involved in the degradation of histamine and its metabolites). However, in total, according to Gene Ontology, proteins and enzymes encoded by more than 200 genes are involved in the histamine pathway. Both temporal and chronic imbalances between the synthesis/intake of histamine and its degradation/metabolism in the human body (including those caused by specific genetic features) mediate the development of inflammatory manifestations with disturbance of the homeostasis of various organ systems (nervous, immune, endocrine, cardiovascular, etc.). Immunopathologic reactions mediated by histamine accompany the development of antigen-specific and nonspecific immediate and delayed-type hypersensitivity reactions of inflammation, effector immunocomplex reactions, autoimmune disorders, and cancer and, ultimately, can determine the comorbidity of common diseases. The review also provides information on the associations of the genes of the histamine pathway with common diseases (according to the studies using the candidate-gene approach and genome-wide association studies).