Chest
Translating Basic Research Into Clinical PracticeScientific Foundations of Allergen-Specific Immunotherapy for Allergic Disease
Section snippets
Immune Mechanisms of Allergic Inflammation
The profound understanding of allergic inflammation is a prerequisite to finding a well-targeted therapy. In the early days, approximately 30 years ago, the allergic inflammation was believed to be solely caused by an imbalance between the effector Th subsets, with Th2 dominance over Th1. Multiple mechanisms that involve all immune system and resident tissue cell responses have become slowly understood over the past decades. In the sensitization phase, the allergens are presented to naive T
Mechanisms of Immune Tolerance to Allergens and AIT: The Role of DCs, T and B Cells in AIT and High-Dose Allergen Exposure
Today, the development of allergy is viewed as the loss of peripheral immune tolerance to allergens, whereas AIT is involved in mechanisms that restore immune tolerance to allergens. IgE is produced but does not cause the disease any more. However, the IgE-to-IgG4 ratio shows a significant change because of the very early increase in allergen-specific IgG4 levels. AIT induces an abundance of allergen-specific and general changes in immune regulatory processes, and various cytokines and cell
AIT in Clinical Settings
A successful AIT starts with the correct identification of patients who are suitable candidates. Immunotherapy vaccines, in general, consist of a mixture of allergen components with a predominance of major allergens. Molecular diagnostics helps to identify individuals who are sensitized to minor allergens or to cross-reactive allergens and who, therefore, may show a different immune response to and clinical benefit from AIT.39 Many large multicenter trials have been published demonstrating that
Future Developments in AIT Vaccines
Safety is certainly an issue for the improvement of SCIT in particular. Although local reactions are apparent in SCIT, ranging from itchy skin to wheal formation in about 5% to 58%,67 they are more frequently encountered in SLIT, where symptoms such as oral itchiness and local swelling are present in > 80%.68 Systemic anaphylactic reactions are more often found in SCIT, with one in > 30,000 injections leading to anaphylaxis compared with only one in 100 million administrations leading to this
Research Needs to Improve AIT
Although attempts to improve AIT have already been made, several issues still need to be addressed in future studies. All steps from diagnosis to follow-up should be considered, starting with patient selection. So far, novel biomarkers and definitions of specific phenotypes are missing. Vaccines can be further improved by standardizing extracts for improved quality and defining their potency in an internationally accepted way. Safety and economic efficiency should be elucidated in various
Conclusions
AIT offers the opportunity to cure wide-spread disease across all continents while preventing the formation of new allergies. There is abundant evidence on clinical safety and efficacy of AIT and its mechanisms of action. Tregs and Bregs appear to be the key immunologic players in restoring tolerance in individuals treated with AIT by producing cytokines such as IL-10 and TGF-β. The skewing of the sole production of allergen-specific IgE toward the noninflammatory IgG4 antibodies is considered
Acknowledgments
Financial/nonfinancial disclosures:The authors have reported to CHEST the following conflicts: Dr Soyka serves on the advisory board of MEDA Pharma but receives no direct financial support. Rhinologic research of his department is supported by MEDA; but there is no conflict with this manuscript. Dr M. Akdis has received research grants from the Swiss National Science Foundation (2012-2015) and two European Union projects: MeDALL and Predicta. Dr C. A. Akdis has received research support from
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Cited by (32)
A randomized trial of subcutaneous allergy immunotherapy in inner-city children with asthma less than 4 years of age
2021, Annals of Allergy, Asthma and ImmunologyCitation Excerpt :Early aeroallergen sensitization and high total immunoglobulin E (IgE) levels in infants and toddlers with recurrent wheezing are strong predictors of persistent asthma with signs of airway remodeling detectable as early as at 4 years of age.2-9 Therefore, infancy may offer a window of opportunity during which immune modulatory treatments could potentially affect disease progression long term, supported by preliminary evidence.10-17 Our study aimed to prospectively determine the efficacy and safety of subcutaneous allergy immunotherapy (SCIT) in inner-city children with atopic asthma aged less than 4 years.
Specific allergen immunotherapy attenuates allergic airway inflammation in a rat model of Alstonia scholaris pollen induced airway allergy
2016, International ImmunopharmacologyCitation Excerpt :This model also provides the opportunity to examine the effect of allergen specific immunotherapy for the induction of immune tolerance as a model for treatment strategy of airway allergy. Currently, allergen specific immunotherapy via both subcutaneous and sublingual route has been shown to reduce allergic diathesis [89,90]. Immune tolerance to allergens is achieved by changes in allergen-specific T and B cell responses in terms of cytokine and immunoglobulin production [91,92].
Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens
2015, World Allergy Organization JournalCitation Excerpt :The disease modification effects of AIT leads to decreased disease severity, less drug usage, prevention of future allergen sensitizations, and a long-term curative effect. Increasing safety while maintaining or even augmenting efficiency is the main goal of research for novel vaccine development and improvement of treatment schemes in AIT [32-34]. Immune tolerance to allergens can be defined as establishment of a long-term clinical tolerance against allergens, which immunologically implies changes in memory type allergen-specific T and B cell responses as well as mast cells and basophil activation thresholds that do not cause allergic symptoms anymore [35-39].
Engineering antigen-specific immunological tolerance
2015, Current Opinion in ImmunologyCitation Excerpt :Early work in immune tolerance induction aimed to deliver antigen in a non-inflammatory context with the goal of loading MHC complexes on immature APCs, which in turn would signal to cognate T cells without co-stimulation through CD40, CD80 or CD86. In addition to its use in allergy desensitization [11] the concept is being pursued clinically in the context of celiac disease, the pseudo-autoimmune disease where wheat and barley-derived proteins induce T cell-mediated intestinal damage. Extensive characterization of the immunogenic epitopes derived from wheat, barley, and rye in celiac patients has found that though heterogeneity in responses do exist, the existence of few conserved immunodominant epitopes among patients might be exploited to induce tolerance toward these and other celiac-relevant epitopes via bystander suppression mechanism [12].
Accelerated subcutaneous immunotherapy in pediatric population – Systematic review
2018, PulmonologyCitation Excerpt :Currently three therapeutic approaches are employed for IgE-mediated respiratory allergies treatment: specific allergen avoidance, symptomatic drugs such as antihistamines, corticosteroids, mast cell stabilizers, antileukotrienes, β2-agonists and anti-IgE monoclonal antibodies, and allergen-specific immunotherapy (SIT). SIT is an immune-modifying therapeutic since it restores mechanisms of immune tolerance to allergens, resulting in a significant reduction of symptoms and symptomatic medication usage, as well as in an improvement of quality of life and productivity at school and/or work.1–4 It is of particular interest in pediatric population because of its capacity to change the response to allergens at an early phase and, thus, to prevent disease progression.5
On the role of allergen-specific IgG subclasses for blocking human basophil activation
2022, Frontiers in Immunology
FUNDING/SUPPORT:The authors' laboratories are supported by Swiss National Foundation [Grant 320030_140772] and the Christine Kühne-Center for Allergy Research and Education, European Seventh Framework Programme projects MeDALL: Mechanisms of the Development of Allergy [261357] and PREDICTA: Post-Infectious Immune Reprogramming and Its Association with Persistence and Chronicity of Respiratory Allergic Diseases [260895]. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.