Allergen-specific immunotherapy is the main pathogenetically substantiated method for the treatment of allergic diseases. It not only leads to a decrease in the clinical symptoms severity, but also has a disease-modifying effect, prevents the progression of the disease, prevents the development of asthma and the spreading of sensitization. Immunological tolerance driven by the allergen-specific immunotherapy is mediated by a complex interaction between various cells of innate and adaptive immunity. Despite the fact that the main mechanisms of allergen-specific immunotherapy have been described to date, the understanding of these processes becomes more detailed at the cellular, molecular and epigenetic levels every year. In turn, a deep understanding of the mechanisms underlying the developing and maintenance of tolerance to allergens during allergen-specific immunotherapy can help reveal predictive biomarkers of efficacy. These biomarkers could streamline the selection of patients by identifying the responders to allergen-specific immunotherapy. This review represents current concepts of the allergen-specific immunotherapy mechanism on various stages of the allergic process. Furthermore, supposed predictive biomarkers of the efficacy are described, taking into account promising directions of research in this area.
Эпигенетика бронхиальной астмы 1 Федеральное государственное автономное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской Федерации, 117997, г. Москва, Российская Федерация 2 Федеральное государственное бюджетное учреждение «Государственный научный центр «Институт иммунологии» Федерального медико-биологического агентства, 115522, г. Москва, Российская Федерация РезюмеБронхиальная астма (БА) -это хроническое воспалительное заболевание дыхательных путей, этиопатогенез которого разнообразен и до сих пор недостаточно изучен. Считается, что важным фактором, связанным с клинической гетерогенностью данного заболевания, являются эпигенетические механизмы регуляции экспрессии генов. В ряде исследований была установлена связь индивидуальных эпигенетических особенностей с предрасположенностью к БА, выраженностью клинических проявлений заболевания, а также с характером ответа на лекарственную терапию. В частности, важными механизмами эпигенетической регуляции воспалительного ответа при БА принято считать метилирование ДНК, регуляцию генетической активности молекулами микроРНК, а также модификацию гистонов. В обзоре рассматриваются эти механизмы в контексте патогенеза и терапии БА и приводится информация об основных методах оценки эпигенетических модификаций. Дальнейшее изучение аспектов эпигенетики БА является актуальным и важным направлением с точки зрения не только фундаментальной науки, но и практической медицины, в связи с возможностью персонификации диагностики и терапии БА.
Laboratory methods of allergy diagnosis are an essential tool in the allergist daily practice. Molecular allergodiagnostics is an advanced examination method that allows detecting the patient individual allergocomponents sensitization. The risk prediction of the severe allergic reactions is the main area of its application, as well as the personalized dietary recommendations creation for food allergy patients. In the determining the appointment of allergen immunotherapy indications clinical and anamnesis data are fundamental, supplemented by the results of traditional methods of allergy examination (skin prick tests or the specific IgE level to whole allergens). The widespread use of such resource-intensive examination as molecular allergodiagnostics for all patients is unjustified before the prescribing allergen immunotherapy. In addition, decisions on the allergen immunotherapy continue or the termination cannot be made based on the change data in the level of clinically relevant specific IgE. At the same time, its use as a third-line diagnostic method can help in solving difficult clinical tasks related to the identification of a causally significant allergen in patients with respiratory allergy symptoms during the seasons of simultaneous dusting of several plants, as well as differentiate the true from the cross-sensitization in polysensitized patients. The molecular allergodiagnostics use will be mandatory in the case of the recombinant therapeutic allergen prescribing, due to the need for a personalized choice of the drug.
Angioedema is caused by a local increase in vascular permeability induced by bradykinin or mast cell mediators. The main challenge of the differential diagnosis of angioedema lies in the fact that different pathophysiological processes may lead to a very similar clinical picture. Moreover, verification of the type of angioedema is crucial for selection of appropriate therapy. In 2020, a school for doctors Chronic urticaria: scientific and medical accomplishments and practical aspects of patient management was held on the basis of the National Research Center Institute of Immunology of the FMBA of Russia as part of the work of the reference center that provides expert assistance to patients with urticaria (GALEN UCARE). A clinical case series of related patients with hereditary angioedema due to a mutation in the PLG gene was presented to demonstrate the challenges of the differential diagnosis between types of angioedema. This article focused on the description of this series.
Allergen immunotherapy is the main method of IgE-dependent allergic diseases pathogenetic treatment which is widely used in the clinical practice. Despite the fact that there is a large amount of randomized placebo-controlled trials data on the allergen immunotherapy efficacy, a number of questions remain unanswered regarding the efficacy of the allergen immunotherapy in real practice. These questions can be answered using real-world evidence. Conducting real-world evidence studies of the allergen immunotherapy it is necessary to follow a strict methodology and to perform the multivariate analysis of the available data. Using of statistical methods reduces the risk of bias. The REACT study is currently the largest and most comprehensive real-world evidence study of the allergen immunotherapy, which included more than 90,000 patients with allergic rhinitis from Germany. The method of statistical adjustment a propensity score match was used to ensure comparable groups and representative obtained data. The REACT study provided results of fundamental clinical and public health significance: the allergen immunotherapy leads to a sustained and long-term medicine prescribing reduction in patients with allergic rhinitis and asthma, improved control of asthma, and also prevents development of exacerbations and respiratory infections in asthma patients. The REACT study is a good quality real-world evidence study with strict methodology and representative results. Further high quality standard studies of real-world data may not only confirm the randomized trials evidence, but also may become a source of new evidence for the allergen immunotherapy efficacy and safety in real clinical practice.
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