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Vol 17, No 4 (2020)

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Climate change and its impact on the development of allergic diseases
Nazarova E.V.

Since the middle of the twentieth century, there has been a widespread increase in the prevalence of allergic diseases, especially in developed countries. Much attention is paid to the changing climate and its influence on the development of allergies, mainly of the respiratory system. In many countries, studies are intensifying to study the relationship of various weather phenomena, air pollution, Earth temperature with the course of certain allergic diseases of the respiratory tract. Global strategies for the treatment and prevention of allergic diseases are being developed. This review provides data from international studies demonstrating the negative impact on human health and the development of allergic diseases of the respiratory system, in particular asthma: a global rise in Earth temperature, air pollution, dust storms, forest fires, dampness in rooms and atmospheric mold, thunderstorms and floods.

Russian Journal of Allergy. 2020;17(4):7-18
Oral food challenges in clinical practice: a missing element of food allergy diagnosis in Russia
Levina D.M., Korsunskiy I.A., Munblit D.B.

Food allergy is one of the most prevalent allergic conditions, causing reduction in patient quality of life. It is linked with high levels of anxiety due to potential life-threatening reactions, and high economic burden for a healthcare system. Food allergy affects approximately 5 to 10% of children around the world. In Russian Federation the diagnosis of food allergy is primarily based on clinical history, laboratory test results, examination and elimination of suspected food. Meanwhile oral food challenge (OFC) is considered a “gold standard” of food allergy diagnosis by most of professional bodies nationally and internationally. OFC is a diagnostic procedure involving administration of a causative allergen in gradually increasing amount under a close medical supervision. The method is safe, highly specific and sensitive and is widely used around the world for more than 45 years. The main goals of OFC include food allergy diagnosis and presence of tolerance evaluation, which may result in diet expansion. OFC may also help establishing both, reaction severity and dose needed to elicit reaction, which may further assist with alleviation of patients’ anxiety. In this paper we discuss existing approaches to the diagnosis of food allergy in Russian Federation and review available recommendations on OFC outlined in international guidelines.

Russian Journal of Allergy. 2020;17(4):19-29
The role of atopy patch test with aeroallergens in allergic diseases diagnostics
Smolnikov E.V., Litovkina A.O., Kolykhalova K.I., Elisyutina O.G., Fedenko E.S.

Allergic diseases are increasingly becoming a global epidemic and pose a considerable and growing public health burden. Allergy is a systemic T2-dependent inflammatory reaction to an allergen that results from a complex interaction between genetic and environmental factors. Allergic diseases occur through a T2-dependent type of allergic reaction, some of them, in particular atopic dermatitis (AD) and asthma, develop involving different types of hypersensitivity or their combination and require revision of allergy diagnostics. Atopy patch test (APT) can be informative in establishing a role of cell-mediated hypersensitivity in pathogenesis of allergic diseases.

The review presents the recent data on the significance of APT in the diagnostics of skin and respiratory allergies.

Russian Journal of Allergy. 2020;17(4):30-37
Modern ideas about mechanisms of allergen-specific immunotherapy
Petrova S.Y., Khlgatian S.V., Berzhets V.М., Petrova N.S., Radikova O.V.

Reviews of domestic and foreign authors consider different approaches to understanding the formation of immunological and clinical tolerance induced by allergen-specific immunotherapy (ASIT). Despite the wide variety of theoretical research, the mechanism of the body’s immune system’s response to ASIT remains unclear.

The aim of this review is to analyze the current understanding of the mechanisms of formation of changes in the body’s reactivity in response to an allergen after ASIT. It is known that the type of response to the antigen is determined by its dose. In low-dose ASIT tolerance to the antigen is formed in the absence of inflammation, which is apparently associated with the activation of specific high-affinity receptors on cells of the immune system. High doses of allergen in ASIT probably lead to a rearrangement of cellular receptors, causing a decrease in their number by internalization or a weakening of their sensitivity to an excessive signal (desensitization). Due to a decrease in the number of receptors and / or their loss of sensitivity, the response to the antigen changes according to the principle of negative regulation, implemented at the level of receptor or postreceptor mechanisms. The formation of an anti-inflammatory cytokine response to antigen contributes to the differentiation of naive T cells into inducible regulatory T cells (iTreg). The suppressing effect of Treg on immune system cells affects Th effector cells, mast cells, basophils, eosinophils, B cells, and dendritic cells.

The occurring immunological shifts form a new type of tolerant response to the allergen, namely, the change in the type of immunoglobulins from IgE to IgG and IgA and new phenotypes of T memory and B memory cells.

Russian Journal of Allergy. 2020;17(4):38-45
Pharmacological profile of antihistamines: focus on unwanted drug interactions
Dukhanin A.S.

Differences between individual antihistamines are determined by such pharmacokinetic properties as the rate and completeness of absorption, half-life, the participation of hepatic and renal mechanisms of elimination from the body. Pharmacodynamic features of the antihistamine include selectivity and affinity for histamine H1-receptors and the presence of central effects. The mechanisms of the development of unwanted drug interactions with second-generation antihistamines are analyzed in detail. Three levels of interaction have been identified: 1) hepatic enzymes of the P450 system; 2) membrane carriers of organic anions (OATP) – transport proteins on the sinusoidal membrane of hepatocytes and the luminal membrane of the epithelium of the proximal nephron tubule; 3) P-glycoprotein (Pgp, ABCB1-protein) of epithelial cells of the small intestine – the area of absorption of oral forms of antihistamines, the epithelium of the proximal tubule and the BBB (blood-brain barrier). The emphasis is made on the description of the dependence of the pharmacological profile of antihistamines on its chemical structure. The “elasticity” of the bilastine molecule, the ability to induce a change in conformation underlies the high complementarity of bilastine to the recognition site of the H1-receptor which is a high affinity. Experimental evaluation confirms this conclusion: the dissociation constant (Dс) of the bilastin-receptor complex is in the nM concentration range. The bilastine molecule, as a representative of antihistamines with zwitterionic properties, carries both a positive and a negative charge at a physiological pH, making it difficult for its penetration into the brain. The peculiarities of the chemical nature of the bilastine molecule are reflected in the specific pharmacological profile of AGP. In vitro studies have shown a high specific affinity of bilastine for H1-receptors with a very low affinity for other histamine receptors (H2, H3, H4), serotonin, bradykinin, muscarinic and adrenergic receptors). According to this indicator, bilastine is 3 times higher than cetirizine and 5 times higher than fexofenadine. Bilastine is practically not metabolized in the body and is excreted mainly unchanged, and also does not have a cardiotoxic effect. Bilastine is well tolerated; as a therapeutic dose it has a less pronounced sedative potential compared to other second-generation antihistamines.


Russian Journal of Allergy. 2020;17(4):46-56
Original studies
Aeropalynologic monitoring of air pollution in the Rostov region: the results of the 2019 season
Churyukina E.V., Ukhanova O.P., Goloshubova E.А.

BACKGROUND: There is an increase in the proportion of patients suffering from allergic diseases caused by the plant pollen. Aeropalinologic monitoring of the air environment allows us to study the composition of aeroallergens and their role in the formation of pollen allergies. Features of the formation of aerial pollen spectra are closely related to the botanical-geographical and natural-climatic conditions of the region. The Rostov region has its own specific features, which is reflected in the qualitative and quantitative composition of pollen rain.

AIM: To study the dynamics of pollination of allergenic plants in Rostov-on-Don, identify the prevailing taxa and create a calendar of pollination of plants for this region.

MATERIALS AND METHODS: Aeroallergens were detected by using a volumetric Burkard trap. The identification of plant pollen and fungal spores was performed by microscopy of colored slides obtained from a sticky tape covered with a special mixture.

RESULTS: In 2019, 21 taxa were registered in the air environment of Rostov-on-don (trees, meadows, haze, cereals, weeds), fungal spores were found in the air, represented by the mold fungi Cladosporium herbarum and Alternaria alternata in high growing concentrations. An increase in the vegetation period of pollination of trees (07.03.–31.06), mares (02.05–03.10), cereals (02.04–14.09), weeds (18.07–28.10) was detected According to the dynamics of pollen concentration, three periods of its growth were registered: spring-summer, summer and summer-autumn. The presence of birch pollen grains in a clinically significant concentration (36 pollen grain (PG)/m3) in this steppe region, an increase in the peak concentration of ragweed (393 PG/m3) in comparison with the same data for 1971 (265 PG/m3) was found.

CONCLUSION: Regional features of the spectrum of air allergens were identified, and a dusting calendar was compiled for Rostov-on-Don.

Russian Journal of Allergy. 2020;17(4):57-65
Chronic spontaneous urticaria in patients over 65 years old
Meshkova R.Y., Vitchuk A.V., Aksenova S.A., Bitutskaya V.V., Volkova E.V., Kovrigina N.V., Slabkaya E.V.

AIM: To study clinical and immunological features in chronic spontaneous urticaria patients aged 65+ and 18–65 yo.

MATERIALS AND METHODS: In total, the study included 494 adult patients with chronic spontaneous urticaria (CSU), who were under our supervision from 2014 to 2019. Depending on the age, the patients were divided into 2 groups according to their age: group 1 included patients over 65 years old (51 subjects, 10.3%); group 2 – patients 18–65 years old (443 subjects, 89.7%). In patients with CSU, angioedema was found with the same frequency regardless of age (group 1 – in 49% of patients, in group 2 – in 58.3%). Female were predominated in both groups (90.2% in the 1st and 85.1% in the 2nd). The duration of CSU exceeding 5 years was less common in elderly patients (in group 1 – 6.8%, in group 2 – 17.7%; p<0.05).

RESULTS: The duration of CSU ranges from 1 to 5 years in most patients regardless of age. The combination of CSU with inducible urticaria is not typical for patients over 65 years old. The analysis of comorbid pathology showed that diabetes mellitus is significantly more common and, less often – autoimmune thyroiditis and allergic rhinitis in patients over 65 years old, in comparison with patients aged 18–65 years old. The influence of the age of patients with CSU on IgG, IgM, IgA, CRP levels in blood serum has not been established. The level of total IgE was significantly lower in patients of the elder age group in comparison with the 2nd group (84.1±18.44 IU/ml and 114.9±11.0 IU/ml; p<0.05, respectively).

CONCLUSION: It is registered that 1/10 of the adult patients with CSU are over 65 years old, and the duration of the disease in them rarely exceeds 5 years. The features of the comorbid pathology in this category of patients have been revealed. The difference in the content of total IgE in patients of different age groups is shown here.

Russian Journal of Allergy. 2020;17(4):66-74
Dynamics of basophil reactivity in the patients with allergic rhinitis on the background of allergen-specific immunotherapy
Barycheva L.Y., Dushina L.V., Golubeva M.V., Minasyan M.M., Medvedenko Y.N.

BACKGROUND: Allergen-specific immunotherapy (ASIT) helps to reduce spontaneous and to induce basophil reactivity, which is one of the major mechanisms of its effectiveness. A number of studies, though, have not confirmed the informative value of the basophil activation test (BAT), in case of ASIT, with house dust mites, meadow grass pollen, and wasp venom. BAT outcomes are likely to be influenced by the properties of the sensitizing allergen, the duration of ASIT, and the BAT markers that are used.

AIMS: To evaluate the basophils reactivity in the patients sensitized to weed pollen and treated with allergen-specific therapy.

MATERIALS AND METHODS: The study involved 60 patients (aged 16–55) with allergic rhinitis sensitized to weed pollen. The diagnosis was based on the skin test outcomes as well as on identifying specific antibodies to major allergens of ragweed, wormwood, timothy, and birch. The pre-seasonal ASIT involved water-salted extracts of pollen allergens during 2 years. Clinical symptoms and the immunotherapy effectiveness were evaluated 6 and 18 months after the ASIT started. BATs were made before the treatment, after the first and second courses of pre-seasonal ASIT, which corresponded to zero, the 3rd and the 15th months of the treatment. The activated basophils were identified based on the CRTH2pos CD203brightCD3neg phenotype.

RESULTS: The first treatment course was completed by 52 patients, while the second one – by 43 patients. A statistically significant decrease in spontaneous basophil reactivity was detected only after the second course of ASIT. The decrease in the allergen-induced basophil activation was identified in 67.4% of the samples obtained after the first ASIT course, and in 67.6% of samples taken after the second immunotherapy course. A decrease in the BAT stimulation index (BAT SI) was identified mainly in the patients featuring positive treatment outcomes.

CONCLUSIONS: ASIT influences on the basophil reactivity indicators in the patients sensitized to weed pollen. The basophil activation test may be considered as a potential predictor of ASIT effectiveness.

Russian Journal of Allergy. 2020;17(4):75-84
Case reports
Modern anti-IgE therapies in children with chronic spontaneous urticaria: clinical cases
Larkova I.A., Revyakina V.A.

The diagnostics and treatment of chronic urticaria is still a pressing problem for specialists of different profiles. Despite the fact that the first line drugs for urticaria treatment are non-sedating H1- antihistamines, there are a number of patients who do not respond to these medications even in their increased doses. This article presents clinical cases of anti-IgE-therapy efficacy in children suffering from urticaria and angioedema.

CONCLUSION: The clinical cases demonstrate current possibilities of successful and safe anti-IgE-therapy of various clinical manifestations of chronic spontaneous urticaria and angioedema in children.

Russian Journal of Allergy. 2020;17(4):85-89
A clinical case of the X-linked moesin deficiency
Latysheva T.V., Latysheva E.A., Setdikova N.H., Esaulova D.R.

With the increasing availability of genetic testing, the population of patients diagnosed with CVID breaks down into groups depending on monogenic defects. There is more and more evidence that adults can have combined immunodeficiencies with a late onset.

This article discusses a clinical case of X-linked moesin-associated immunodeficiency (X-MAID). This is a recently described immunodeficiency, which mostly manifests itself at an early age with severe lymphopenia and hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, a weak immune response to vaccine antigens, and increased susceptibility to bacteria and type 3 human herpesvirus.

X-MAID, X-linked immunodeficiency with a recessive mode of inheritance, is caused by genetic defects in the MOESIN gene (membrane organizing spike elongation protein, MSN). Until recently, there were records of 10 people with this mutation, 9 of which have the phenotype of severe combined immunodeficiency (SCID). The patient described in this article has been under observation since the age of 12 and diagnosed with SCID due to an IgG decrease accompanied by infectious-purulent processes of the respiratory tract and diarrheal syndrome.

However, the patient did not entirely fit into the typical clinical picture of CVID due to a severe therapy-torpid papillomavirus infection, the increased number of switched memory B-cells, IgG isolated decrease, persistent severe leukopenia and lymphopenia of CD4+ cells. In accordance with the clinical picture and the results of the immunological examination, combined immunodeficiency was surmised. After a full exome DNA sequencing chrX: g.64951012C> T missense type mutation was found in exon 5 of the MSN gene (change in the ENSP00000353408.5:p.Arg171Trp protein). X-MAID was therefore confirmed.

Of the 9 described patients with a similar mutation, 8 had a clinical picture of severe combined immune deficiency. This clinical case confirms the possibility of a milder clinical phenotype development with a late onset under the guise of CVID and shows the need for molecular genetic examination of the adult population of patients with impaired antibody synthesis. The verification of the diagnosis allows not only to determine the prognosis and tactics of the therapy, but also to carry out genetic family counseling and to offer a possibility of giving birth to healthy offspring.

Russian Journal of Allergy. 2020;17(4):90-94
Help to the practitioner
Vitamin D and chronic spontaneous urticaria: searching for algorithms of personalized therapy
Kukes I.V., Borzova E.Y., Nenasheva N.M., Sychev D.A.

Today, we can see a great interest in vitamin D because it participates in the regulation of many metabolic processes, and its deficiency is associated with the development of various diseases. Chronic spontaneous urticaria (CSU) is the disease that affects the quality of patient’s life, and the existing strategy of patient management is not always sufficiently effective. Nowadays, there is enough information about the role of vitamin D deficiency and the severity of CSU. That is why it is important to study not only therapeutic schemes, but also a role of genetic variability that may have an impact on vitamin D levels.

Such studies will help to personalize the treatment schemes for patients with CSU. At the same time, the focus of these studies should be not only on the receptor and vitamin D binding protein, but also on P450 system, which plays a key role in the vitamin D metabolism.

Russian Journal of Allergy. 2020;17(4):95-101

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