Vol 16, No 3 (2019)

This review presents current data on the associative relationships of genes of the major histocompatibility complex (HLA) and other genes with atopy. Despite the long history of studying the role of HLA class genes in atopy and the introduction of modern technologies and methods, many unresolved issues remain, including the difficulties caused by the heterogeneity of the human population, the complex structure and disequilibrium of linkage between different HLA genes. Although phenotypic heterogeneity is considered as the main limitation in understanding the genetic determinants of atopy, only a few studies have examined the relationships of its typical clinical manifestations induced by aeroallergens with certain HLA genes. The identified molecular mechanisms and genetic characteristics open up the possibility of using new therapeutic targets and modifying existing drugs.

Background. Allergen-specific immunotherapy (ASIT) is viewed as the only treatment that influences all patho-genetically significant parts of the allergic process in the initial and late phases of the IgE-mediated allergic reaction and modifies the abnormal immune reactivity to a specific allergen. Currently, sublingual (SLIT) and subcutaneous (SCIT) immunotherapy are most commonly used in clinical practice. Despite long experience of sublingual and subcutaneous immunotherapy application, questions remain about the preferred ASIT method and comparative effectiveness of different ASIT methods. This article evaluates the efficacy, benefits of SCIT and SLIT and highlights new findings related mechanisms and potential biomarkers. The aim of the study. To evaluate the comparative efficacy of different methods of ASIT (subcutaneous and sublingual) based on clinical data and biomarkers in the blood serum and other biological fluids in adult patients with allergic rhinoconjunctivitis (with/without asthma). Materials and methods. 60 patients with allergic rhinoconjunctivitis (with/without asthma) aged 18 to 50 were randomly assigned to 3 groups treated by sublingual immunotherapy with extracts of allergens, subcutaneous immunotherapy with extracts of allergens and subcutaneous with modified allergens (allergoids) respectively. Results. The efficiency of the first course of preseason ASIT (SCIT and SLIT) with extracts of allergens and aller-goids in the control of symptoms of allergic rhinoconjunctivitis (with/without asthma) was demonstrated. After the end of the first year pre-season ASIT data analysis scales (Total Symptom Score -TSS, Medircation Score -MS) revealed the best performance in the group of patients receiving SCIT with allergoids compared with patients receiving the SLIT with extracts of allergens: the scales of the TSS (p=0.023), MS (p=0.002). In addition, at the end of the maintenance phase of ASIT in patients treated with SCIT with allergoids the level of eosinophilic cationic protein (ECP) in the nasal lavage decreased by 22% (p=0.012), secretory immunoglobulin A (sIgA) in the nasal lavage increased by 70% (p=0.001), interleukin-10 (IL-10) in serum increased by 126% (p=0.006), allergen-specific IgG4 increased by 42% (p=0.01) from the initial values, that correlates with a decrease in the severity of clinical manifestations. In pollen season ECP level in nasal lavage was significantly (p=0.007) lower in a group of patients who received SCIT with allergoids compared with patients who received the SLIT with extracts of allergens. The most significant changes of serum level of IL-10 in the pollen season occurred in a group of patients receiving SCIT with allergoids compared with patients who received SLIT (p=0.013) and SCIT (p=0.001) with extracts of allergens. Conclusion. The study results deepen the existing understanding of the mechanisms of SCIT and SLIT. They allow to develop a comprehensive assessment of the therapy efficacy scheme based on clinical parameters and on monitoring of local (ECP, sIgA) and systemic biomarkers (IL-10, allergen-specific IgG4) as well.

Expansion of the range of examined T-helper clones has determined more complex immune mechanisms for the implementation of allergic inflammation. Objective. To characterize the parameters and relationships between the serum cytokine profile and T-lympho-cyte subpopulation in peripheral blood of children with bronchial asthma and allergic rhinitis. Materials and methods. 150 children aged between 3-11 years old with bronchial asthma, and allergic rhinitis and 30 healthy volunteers were examined. Immunological parameters were assessed by flow cytometry, the concentration of serum interleukins and IgE were determined by means of enzymelinked immunosorbent assay. Statistical analysis was performed with «Statistica 10» program with a critical level of significance p<0.05. Results. High levels of interleukins -4, -8, -13, 17A were determined, IL-7F level was not significantly different from that in control group and low level of IFN-y was found in the serum of children with allergic diseases. The number of CD3+CD8+CD45RO+, CD3+CD8+CD45RACD45RO+ T-lymphocytes, CD3+CD4+ T-helper cells and Th17 were increased and at the same time CD3+CD4+CD45RO+ memory cells were decreased In bronchial asthma and allergic rhinitis children. Number of Th17 cells in healthy children was 9.49±1.6%, in allergic children it was significantly higher - 14.5±0.77% (p<0.001). Analyses of serum cytokine count in children with isolated BA and in association with allergic rhinitis revealed multidirectional correlations differing in strength and direction from those in the group of healthy children. Conclusion. In children with isolated bronchial asthma and associated with allergic rhinitis the following parameters were found: CD3+CD4+ T-cells count was comparable to that in healthy children, the imbalance of T-helper subpopulation: prevalence of Th2 and Th17, activation of IL-17A, IL-4, IL-8, IL-13 synthesis and low level of serum IFN-y.

Bronchial asthma (BA) is one of the most common chronic diseases, characterized by airway inflammation and bronchospasm. Symptoms of BA are wheezing, shortness of breath, a feeling of constriction in the chest and cough, the frequency and severity of which vary greatly over time. Today studies of BA phenotypes allow selecting treatment depending on the particular pathogenesis of each phenotype individually, thereby helping to achieve control, which is the main goal of BA therapy. However, it is necessary to take into account the peculiarities of airway innervation, since an increased parasympathetic tone is characteristics of all BA phenotypes and plays an important role in the development of bronchoconstriction and inflammation. Therefore, tiotropium bromide, which is a long-acting blocker of muscarinic cholinergic receptors, is one of the main bronchodilators in the treatment of BA. It blocks bronchoconstriction, hypersecretion and swelling of the mucous membrane of the airway, which in turn prevents the progression of inflammation, and the prolonged action of tiotropium bromide, which allows it to be used once a day helps to achieve control of asthma in addition to basic inhalation therapy - inhaled corticosteroids (ICS) long-acting P2-agonists (LABA). According to GINA (Global Initiative for Asthma), tiotropium bromide is recommended as an additional treatment, starting from step 4, and in accordance with the Russian Federal Clinical Guidelines for Bronchial Asthma - from step 3. Currently, according to clinical studies, much is known about the mechanisms of action and biological properties of tiotropium bromide, which made it possible to substantiate the needs for its administration to patients with BA regardless of its phenotype. This strategy will contribute to a more successful control of BA considering risk factors and comorbidity, thereby reducing needs of increasing ICS dose.

Hypersensitivity reactions to iodinated contrast media are a pressing public health issue. Lack of understanding of pathogenetic mechanisms of such reactions leads to unjustified refuse of diagnostic and therapeutic procedures using iodinated contrast agents. Reactions of hypersensitivity to other iodine-containing medications are not a contraindication for use of contrast agents. Skin allergy tests are only performed in the patients who had a history of allergic reactions to iodinated contrast media. Usually it is possible to determine an alternative agent by means of skin tests. Premedication before a contrast-enhanced radiological examination has to be indicated to all patients with previous history of allergic disease.