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.
Представлен обзор современных исследований, посвященных недавно открытому явлению-феномену энтопии (локальной атопии), с точки зрения его фенотипов и эндотипов. Клиническим вариантом эндотипа энтопии является локальный аллергический ринит, новая патология,-объект исследований в современной иммунологии, аллергологии и оториноларингологии. Точные механизмы срыва толерантности к аллергенам при энтопии остаются неясными. Между тем феномен энтопии может стать ключом для расшифровки нерешенных вопросов срыва аллергической толерантности в разных анатомических сайтах. Обзор посвящен патогенезу, диагностическому алгоритму и проблеме выбора терапевтических подходов при локальном аллергическом рините. Ключевые слова: aллергены, aтопия, энтопия, толерантность к аллергенам, aллергический ринит, локальный аллергический ринит, фенотипы, эндотипы, биомаркеры, Т-хелперы 2-го типа, T-регуляторные клетки. Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи. Источник финансирования. Авторы заявляют об отсутствии финансирования.
Over the last decade the role of innate immunity has been known to be crucial for the activation of adaptive immune system. The main triggers that upregulate reactions of innate immunity are small exogenous molecules with conserved motifs, molecular patterns. The article discusses a variety of possible roles of molecular patterns in the immune mechanisms, including the participation of Allergen Associated Molecular Patterns (AAMPs) in allergic processes.
The review focuses on allergen-specific immunotherapy (AIT), a treatment method for atopic diseases, including allergic rhinitis. The theoretical and practical basics, development prospects, indications and contraindications to AIT, peculiarities of AIT execution in allergic rhinitis, and tolerogenic effects of immunotherapy are considered. Advantages and disadvantages of each of the two preferable routes of allergen administration in AIT, subcutaneous and sublingual, are described. The main goals of further AIT advancement include shortening of treatment protocols with no significant loss of efficacy, creation of a safer adverse effect profile, and distribution of AIT in developing countries.
Local allergic rhinitis, a new endotype of allergic rhinitis discerned by researchers of the Spanish Allergy School, is now in the focus of interest of international allergological community. A special feature of local allergic rhinitis, which, being similar to conventional signs of allergic rhinitis, is, however, characterized by absence of systemic atopy manifestations, e.g., an increased total serum IgE content and positive allergic skin tests. In order to assess the level of tolerance breakdown to allergens in local and classical allergic rhinitis, we have studyed concentrations of IL-4, IL-22, and IFNγ in three biological fluids, blood, nasal secretions, and skin exudate. The whole study cohort consisted of 82 patients aged 18 to 60 years with established allergic rhinitis. The diagnosis was based on counseling by allergologist/immunologist, including clinical case history and possible inheritance of atopy as well as videorhinoscopy performed by an ENT specialist. The procedure of videorhinoscopy allowed to specify allergic origin of rhinitis and exclude the patients with non-allergic forms of the disease, but it did not enable us to differentiate between the endotypes of classic and local allergic rhinitis. Subsequently, all patients have been divided into two subgroups based on the criteria of systemic atopy: (1) with a high content of serum total IgE and positive skin allergy tests (n = 41) and (2) with a significantly lower concentration of IgE and negative allergy tests (n = 41). It was concluded that the patients with classic allergic rhinitis prevailed in the 1st subgroup, whereas local rhinitis predominated in the 2nd group. The study of IL-4, IL-22 and IFNγ concentrations in the three biological fluids allowed us to presume that the 1st subgroup was characterized by increased content of IL-4 and IL-22 in blood and skin exudate in comparison with controls, and the 2nd subgroup showed a decrease in IFNγ to control values. The cytokine concentrations in nasal secretions were not representative for the subgroups studied. The result has been interpreted as the absence of tolerance breakdown to causal allergens in the patients with local allergic rhinitis at the systemic level. The obtained data could be used in development of a diagnostic biomarker system for this specific endotype of allergic rhinitis, thus avoiding potential diagnostic errors which occurred in the past, when this endotype was classified as non-allergic form of the disease, thus administering non-adequate treatment, e.g., allergen-specific immunotherapy, which could be prescribed in these cases.
РЕЗЮМЕЛокальный аллергический ринит является новой атопической болезнью в современной аллергологии и ринологии. Его клинические симптомы в настоящее время хорошо описаны с проведением сравнения с классическим аллергическим ринитом, но диагностические и терапевтические протоколы, включая аллерген-специфическую иммунотерапию, еще уточняются.Таким образом, локальный аллергический ринит остается недостаточно диагностированной патологией и по ошибке часто относится к группе неаллергических ринитов. Однако патогенез и особенно механизмы срыва аллергенной толерантности при этом эндотипе аллергического ринита остаются неизученными. Продолжаются исследования сети протолерогенных клеток и молекул, включая Т-регуляторные клетки, протолерогенные дендритные клетки, интерлейкин (IL)-10, IL-35, трансформирующий фактор роста b, вегетативную иннервацию носа и нейротрансмиттеры.Цель настоящего обзора сфокусирована на диагностических маркерах локального аллергического ринита.Ключевые слова: локальный аллергический ринит, видеориноскопия, назальный провокационный тест, специфические назальные иммуноглобулины, тест активации базофилов.Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи.Источник финансирования. Авторы заявляют об отсутствии финансирования.
The role of transforming growth factor β (TGF-β) in atopic dermatitis pathogenesis is discussed basing on the analysis of existing data of cellular and molecular mechanisms of allergic inflammation. Up-to date data of the main T-helper (T-h) lymphocyte subpopulations including Tx1, Tx2, Tx3 has been presented. Functions of regulatory T-cell populations and produced cytokines have been described. The main attention has been accented on the TGF-β structure and biological activity as a main Tx3 cytokine. The current information of TGF-β influence on different cell populations and its biological activity realization mechanism is thoroughly discussed. Information relating to the mechanism of cytokine regulation during atopic dermatitis has been summarized. A deep analysis of possible participation of TGF-β in disbalance formation on Tx1 and Tx2 levels, in disturbances of histological derma structure and allergic inflammation timing has been made.
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