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      Mechanisms and biomarkers of successful allergen-specific immunotherapy

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          Abstract

          Allergen-specific immunotherapy (AIT) is considered the only curative treatment for allergic diseases mediated by immunoglobulin E (IgE). Currently, the route of administration depends both on the different types of causal allergens and on its effectiveness and safety profile. Several studies have reported the mechanisms and changes in humoral and cellular response underlying AIT; however, the full picture remains unknown. Knowledge of who can benefit from this type of treatment is urgently needed due to the patient safety risks and costs of AIT. In vivo or in vitro biomarkers have become a strategy to predict clinical outcomes in precision medicine. There are currently no standardized biomarkers that allow determining successful responses to AIT, however, some studies have found differences between responders and nonresponders. In addition, different candidates have been postulated that may have the potential to become biomarkers. In this review, we aim to summarize the findings to date related to biomarkers in different IgE-mediated allergic diseases (respiratory, food, and venom allergy) with the potential to define who will benefit from AIT.

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          Most cited references214

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          Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision.

          Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update.
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            Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR

            CD4+ T regulatory (Treg) cells are central to immune homeostasis, their phenotypic heterogeneity reflecting the diverse environments and target cells they regulate. To understand this heterogeneity, we combined single-cell RNAseq, activation reporter and TCR analysis to profile thousands of Tregs or Tconvs from mouse lymphoid organs or human blood. Treg and Tconv pools showed areas of overlap, as resting “furtive” Tregs with overall similarity to Tconv, or as a convergence of activated states. All Tregs express a small core of FoxP3-dependent transcripts, onto which additional programs are added less uniformly. Among suppressive functions, Il2ra and Ctla4 were quasi-constant, inhibitory cytokines being more sparsely distributed. TCR signal intensity didn’t affect resting/activated Treg proportions, but molded activated Treg programs. The main lines of Treg heterogeneity in mice were strikingly conserved in human blood. These results reveal unexpected TCR-shaped states of activation, providing a framework to synthesize previous observations about Treg heterogeneity.
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              The Atopic March: Progression from Atopic Dermatitis to Allergic Rhinitis and Asthma

              The development of atopic dermatitis (AD) in infancy and subsequent allergic rhinitis and asthma in later childhood is known as the atopic march. This progressive atopy is dependent on various underlying factors such as the presence of filaggrin mutations as well as the time of onset and severity of AD. Clinical manifestations vary among individuals. Previously it was thought that atopic disorders may be unrelated with sequential development. Recent studies support the idea of a causal link between AD and later onset atopic disorders. These studies suggest that a dysfunctional skin barrier serves as a site for allergic sensitization to antigens and colonization of bacterial super antigens. This induces systemic Th2 immunity that predisposes patients to allergic nasal responses and promotes airway hyper reactivity. While AD often starts early in life and is a chronic condition, new research signifies that there may be an optimal window of time in which targeting the skin barrier with therapeutic interventions may prevent subsequent atopic disorders. In this review we highlight recent studies describing factors important in the development of atopic disorders and new insights in our understanding of the pathogenesis of the atopic march.
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                Author and article information

                Journal
                Asia Pac Allergy
                Asia Pac Allergy
                APA
                Asia Pacific Allergy
                Asia Pacific Association of Allergy, Asthma and Clinical Immunology
                2233-8276
                2233-8268
                October 2022
                31 October 2022
                : 12
                : 4
                : e45
                Affiliations
                [1 ]Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
                [2 ]Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
                [3 ]Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul National University, Seoul, Korea.
                Author notes
                Correspondce to Willem van de Veen. Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Herman-Burchard-Strasse 9, CH-7265 Davos-Wolfgang, Switzerland. willem.vandeveen@ 123456siaf.uzh.ch
                Author information
                https://orcid.org/0000-0002-9993-9530
                https://orcid.org/0000-0002-7352-7204
                https://orcid.org/0000-0001-9540-7759
                https://orcid.org/0000-0002-8025-7134
                https://orcid.org/0000-0001-7620-1077
                https://orcid.org/0000-0001-8925-1786
                https://orcid.org/0000-0002-2572-5302
                https://orcid.org/0000-0003-3157-0447
                https://orcid.org/0000-0003-0554-9943
                https://orcid.org/0000-0001-8020-019X
                https://orcid.org/0000-0001-9951-6688
                Article
                10.5415/apallergy.2022.12.e45
                9669467
                36452016
                9b496144-f32b-4699-84f8-c50a35c15cd6
                Copyright © 2022. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 October 2022
                : 30 October 2022
                Categories
                Current Review

                Immunology
                allergen-specific immunotherapy,allergy,biomarkers,ige,regulatory t cells,regulatory b cells

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